Trial DesignRationale and design of the school-based SI!
Program to face obesity and promote health
among Spanish adolescents: A cluster-
randomized controlled trial
Rodrigo Fernandez-Jimenez, MD, PhD, a,b,c Gloria Santos-Beneit, PhD, a,d Anna Tresserra-Rimbau, PhD, e,f
Patricia Bodega, MSc, a,d Mercedes de Miguel, MSc, a,d Amaya de Cos-Gandoy, MSc, a,d Carla Rodríguez, MSc, d
Vanesa Carral, PhD, d Xavier Orrit, PhD, a,d Domènech Haro, BSc, d Isabel Carvajal, MSc, d Borja Ibañez, MD, PhD, a,b,g
Carolina Storniolo, PhD, f,hMónicaDomènech,MD,PhD, f,i RamonEstruch,MD,PhD, f,i JuanMiguel Fernández-Alvira, PhD,a
Rosa Maria Lamuela-Raventós, PhD, f,h and Valentin Fuster, MD, PhDa,c Madrid, Barcelona, Reus Spain and New York,
United StatesBackground Unhealthy habits in adolescents are increasing at an alarming rate. The school offers a promising
environment in which to implement effective preventive strategies to improve adolescents' lifestyle behaviors. The SI! Program is
a multilevel multicomponent school-based health-promotion intervention aimed at all stages of compulsory education in Spain.
We present the study design of the SI! Program for Secondary Schools, targeting adolescents aged 12 to 16 years.
Aim The main goal of this study is to evaluate the impact of the SI! Program educational intervention on adolescent lifestyle
behaviors and health parameters.
Methods The study was designed as a cluster-randomized controlled intervention trial and enrolled 1326 adolescents
from 24 public secondary schools in Spain, together with their parents/caregivers. Schools and their students were randomly
assigned to the intervention group (the SI! curriculum-based educational program over 2 or 4 academic years) or to the control
group (usual curriculum). The primary endpoint will be the change from baseline at 2-year and 4-year follow-up in the
composite Ideal Cardiovascular Health (ICH) score, consisting of four health behaviors (body mass index, dietary habits,
physical activity, and smoking) and three health factors (blood pressure, total cholesterol, and glucose). Secondary endpoints
will include 2-year and 4-year changes from baseline in ICH score subcomponents, the Fuster-BEWAT health scale, adiposity
markers (waist circumference and body composition), polyphenol and carotenoid intake, and emotion management.
Discussion The overarching goal of the SI! Program is to instill healthy behaviors in children and adolescents that can be
sustained into adulthood. The SI! Program for Secondary School is a comprehensive health-promotion intervention targeting
12–16-year-old adolescents and their immediate environment. The present study addresses the optimal timing and impact of
the educational intervention on health in adolescence. (Am Heart J 2019;215:27-40.)rom the aCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain,
Centro de Investigación Biomédica En Red en enfermedades CardioVasculares
IBERCV), Madrid, Spain, cThe Zena and Michael A. Wiener Cardiovascular Institute,
ahn School of Medicine at Mount Sinai, New York, United States, dFoundation for
cience, Health and Education (SHE), Barcelona, Spain, eHuman Nutrition Unit, University
ospital of Sant Joan de Reus, Department of Biochemistry and Biotechnology, Faculty of
edicine and Health Sciences, Pere Virgili Health Research Center, Universitat Rovira i
irgili, Reus, Spain, fBiomedical Research Networking Center-Physiopathology of Obesity
nd Nutrition (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Government of Spain,
adrid, Spain, gIIS-Fundación Jiménez Díaz Hospital, Madrid, Spain, hDepartment of
utrition, Food Science and Gastronomy, School of Pharmacy and Food Sciences, XaRTA,
SA, University of Barcelona, Barcelona, Spain, and iDepartment of Internal Medicine,
ospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),
niversity of Barcelona, Barcelona, Spain.
CT# NCT03504059.
rial registration: ClinicalTrials.gov identifier NCT03504059. Registered (https://
linicaltrials.gov/show/NCT03504059).
ources of funding: This study was supported by the Fundació la Marató de TV3 (369/C/
016), the “la Caixa” Foundation (LCF/PR/CE16/10700001), and the SHE Foundation.
VF is a recipient of funding from the American Heart Association under grant No
14SFRN20490315. R.F-J is a recipient of funding from the European Union Horizon 2020
Research and Innovation Programme under Marie Skłodowska-Curie grant No 707642.
We would like to thank the Ministerio de Ciencia, Innovación y Universidades for
supporting the project AGL2016–75329-R; and Generalitat de Catalunya. The CNIC is
supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y
Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of
Excellence (SEV-2015-0505).
Submitted December 17, 2018; accepted March 28, 2019.
Reprint requests: Valentin Fuster, MD, PhD, Centro Nacional de Investigaciones
Cardiovasculares (CNIC), Melchor Fernández Almagro, 3. 28029, Madrid, Spain. or
Rosa M Lamuela-Raventós, PhD, Department of Nutrition, Food Sciences and Gastronomy,
XaRTA, INSA-UB, School of Pharmacy and Food Sciences, University of Barcelona,
Barcelona, Spain.
E-mail: lamuela@ub.edu
0002-8703
© 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.ahj.2019.03.014F
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28 Fernandez-Jimenez et al
American Heart Journal
September 2019Cardiovascular disease (CVD) is the leading cause of
death and disability in the world,1 largely because of risk
factors modifiable by changes in behavior.2,3 Behavioral
risk factors start in childhood and adolescence,4-6 and
lack of physical activity7 and an unhealthy diet8 in
particular have contributed significantly to the growing
problem of youth obesity.9-11 This will manifest as an
increased CVD risk decades later.12-14 Early prevention
interventions able to positively impact health-related
behaviors in young people represent one of the most
promising approaches to combating obesity and promot-
ing health and thereby preventing CVD in adulthood.15-18
The school is probably the most appropriate setting for
such an intervention19-21 because no other institution has
as much influence on children during their first two
decades of life.22 Adolescence is a critical period for the
initiation of unhealthy behaviors. Few school-based
interventions have been tested in randomized trials
targeting adolescents, suggesting mild effectiveness.23-25
Most studies focused on a single lifestyle component and
targeted weight loss rather than overall health promotion.
The elements identified as necessary for an effective
intervention include evidence-based approaches;26,27 de-
velopment of personal, social and emotional abilities;28 and
a focus on the students, their families, and the school.29,30
The SI! Program (Salud Integral - ComprehensiveHealth)
is amultidimensional educational intervention, designed by
the SHE Foundation, that adapts principles of the
Transtheoretical Model of Change31 to promote lifelong
cardiovascular health and good quality of life by instilling
healthy lifestyle behaviors from early childhood through to
adolescence.32-35 The intervention adopts a multicompo-
nent approach to health that, unlike many childhood
interventions in school-age adolescents, goes beyond the
prevention of obesity through fitness education or dietary
advice.36 Uniquely, the intervention introduces emotion
management as a cohesive component aimed at enhancing
the uptake of healthy behaviors and instilling protective
behavioral mechanisms against substance abuse.
In this article, we describe the rationale, objectives, and
methods used to design the SI! Program for Secondary
Schools, a cluster randomized intervention trial aimed at
promoting health and combating obesity among Spanish
adolescents.
Study objectives
The main objectives of the SI! Program for Secondary
Schools are as follows: (1) to characterize lifestyle
behaviors (dietary habits, physical activity and sedentary
patterns, smoking and substance abuse, and emotion
management) and health parameters among adolescents
aged 12 to 16 years in a large sample of schools in Spain;
(2) to evaluate the impact of different timings and
intensities of the SI! Program educational intervention
on adolescent lifestyle behaviors and health; (3) to studythe association between lifestyle behaviors, with special
focus on dietary and physical activity habits, obesity, and
other clinical parameters; and (4) to study the influence
of the school environment and sociodemographic and
lifestyle characteristics at the family level on adolescent
lifestyle behaviors and health change.
Methods
Study design, population, and randomization process
The SI! Program for Secondary Schools study was
designed as a cluster-randomized controlled intervention
trial in which the units of randomization were the
participating schools. Secondary schooling in Spain in-
cludes education for adolescents aged from 12 to 16 years
in grades 1 to 4. The eligible schools must meet all the
inclusion criteria: status as a public school located in
Barcelona or Madrid, provision of education from grades 1
through 4, and 3 to 5 classes in grade 1. The study aimed to
enroll 24 secondary schools and a minimum of 1200
adolescents. To evaluate the effects of two different
exposures to the program, schools were randomly
allocated for intervention in all secondary-school levels
(long-term intervention group) or only the first 2 levels
(grades 1 and 2; short-term intervention); a group of control
schools continued with their usual curriculum (Figure 1).
The Barcelona and Madrid regional government educa-
tion committees invited all head teachers from eligible
schools (n = 146) to a presentation of the SI! Program
study design. The final 24 schoolswere those that agreed to
participate, and they were subsequently allocated 1:1:1 to
one of the two intervention arms or to the control group
using a simple randomization scheme, thus ensuring an
equal number of schools in each study arm. The allocation
sequence was generated by an independent researcher
who has no interaction with schools or participants during
the study. Schools were informed of their allocation group
by e-mail. Within each school, the study included those
adolescent students and their parents or legal guardians
who signed the informed consent form.
In the 24 schools, all 1st grade students and their
families were invited to participate. Informed consent
forms were provided to the teachers, who distributed
them to parents, collected the completed forms, and
returned them to the research team. Additional consent
was provided for dual energy X-ray absorptiometry
(DEXA). Upon completion of this process, the participant
was considered enrolled in the study. The actual flow
chart of the study schools and adolescent participants is
shown in Figure 2. Participating parents or caregivers,
adolescent students, and school boards have the right to
withdraw from the study at any time. Based on adherence
criteria established by the SHE Foundation coordination
team, schools unable to deliver 75% of the program
curriculum may be excluded from the study. Whether
they are in an intervention arm or control arm,
Figure 1
Study design of the SI! Program for Secondary Schools.
Fernandez-Jimenez et al 29
American Heart Journal
Volume 215participating schools are discouraged from running
concomitant health-related programs during the course
of the trial. Participating schools are advised to inform
investigators about interest in any other health-related
programs, and investigators additionally monitor these
periodically.
The study was approved by the Committee for Ethical
Research (CEI) of the Instituto de Salud Carlos III in
Madrid (CEI PI 35_2016) and by the CEI of the Fundació
Unió Catalana d'Hospitals in Barcelona (CEI 16/41) and the
University of Barcelona Bioethics Committee
(IRB00003099). Data will be collected and handled
according to Spanish Law 15/1999 on the Protection of
Personal Data, ensuring the confidentiality of all partici-
pants' data. The study is registered at ClinicalTrials.gov,
number NCT03504059. The reporting of this study
protocol adheres to the SPIRIT guidelines.37,38 The authors
are solely responsible for the drafting and editing of the
manuscript and its final contents. There was no specific
funding provided for the creation of this manuscript.
Intervention
The levels and components comprising the educational
and behavioral intervention are summarized in Table I.
The SI! Program for Secondary Schools is tailored to the
curriculum content at this educational stage, with
adaptation of strategies and materials. Materials were
developed by the SHE Foundation using innovative
teaching methodologies39 aimed at inculcating a criticalattitude among adolescents, and thereby leading to better
self-control of their own behavior.40 The intervention
materials, strategies and assessments were tested during
2017 in 2 pilot schools in Barcelona and Madrid. The
teachers implementing the SI! Program in their classes
completed a survey with specific questions about the
program activities. The results of this pilot study (not
published) helped to finesse the intervention materials
and strategy before starting the randomized trial.
Adolescent-level intervention. The core interven-
tion consists of teacher-led computer-based simulations
and games (virtual trip) targeting the different age groups
(grades 1-2 or 1-4). The minimum intervention load is 18
hours per year in the short-term intervention group and
12 hours per year in the long-term intervention group.
The health challenge topics (healthy eating, physical
activity, and substance abuse avoidance) are integrated
into the regular curricular subjects (science, physical
education, etc.) and are designed to stimulate a range of
motivational pathways related to the diverse content
through a shared methodology. The classroom activities
are carried out in 3 teaching units per academic year,
each focused on healthy eating, physical activity, or
substance abuse avoidance (protective factors). For the
healthy eating unit, the classroom intervention mostly
focuses on the Mediterranean diet pyramid, the recom-
mended quantities of different food types, alternatives to
sugar-sweetened drinks, the healthiest kinds of dietary
fats, food labeling, and emotional eating. For the physical
Figure 2
SI! Program for Secondary Schools flow chart.
30 Fernandez-Jimenez et al
American Heart Journal
September 2019activity unit, the classroom intervention tackles learning
different sports, discovering abilities, planning training
sessions, learning about the benefits of aerobic activities,
and the importance of rest. Lastly, for the protective
factors unit, participating adolescents work mainly on
self-esteem, assertiveness, and self-efficacy. The interven-
tion provides strategies to identify and deal appropriately
with emotions such as stress and anxiety. The students
also learn how to identify talents and hobbies that
support healthy leisure activities. Body acceptance is
integrated into all activities in the 3 teaching units. At the
end of each main activity, students complete a diary
describing what they have learned.
The educational resources for the intervention are intro-
duced through an interactive game (to be downloaded on apersonal computer,mobile phone, or tablet). In the game, the
student, through a personalized avatar, embarks on a virtual
trip, during which he or she faces a series of challenges.
Individuals earn points by registering their out-of-school
physical activity, and these points are converted to kilometers
for the virtual trip. Additional points can be awarded by the
teacher based on each student's participation in the different
programactivities in the classroom.The teachers can also give
additional rewards as the students reach specific points
milestones. All the teachers in the intervention group have
online access to thematerials and adetailed teaching guide via
the SI! Program website (schools are provided with a
password at the beginning of the academic year).
Family-level intervention. The family-level interven-
tion will be carried out through three newsletters per
Table I. SI! Program for Secondary Schools: Levels of intervention and goals.
Level Goal Strategy Supporting Materials
Adolescents Instill a healthy lifestyle Healthy activities at school and
physical activity out of school
- Web app for recording extra-curricular physical activity.
- Classroom materials: teaching units, including audiovisual
resources, games, etc.
- Health Fair
Families Instill a healthy lifestyle Newsletters with recommendations
Participation in the school Health Fair
- Newsletters related to nutrition, physical activity and
protective factors
- SI! Program website
- Health Fair
Teachers Instill healthy lifestyle
contents in the curriculum
Formal training
Continued counseling from the SHE
Foundation educational team
- Teaching guide classroom materials
- Proposal for the Health Fair
- SI! Program website
School environment Promote a healthy school
environment
Health recommendations for schools - Healthy School Management
- Guidance for the Healthy Fair
- SI! Program web site
Fernandez-Jimenez et al 31
American Heart Journal
Volume 215course related to nutrition, physical activity, and protec-
tive factors. The content is focused on improving parents'
knowledge about key messages in these areas and how
they can help to instill healthy habits in their children.
Teacher-level intervention. At least one teacher at
each school will receive training in the promotion of
cardiovascular health in the school setting. This health
coordinator will be the role model for the other
participating teachers. All of the team will work together
on the program activities.
School environment-level intervention. For the
school-level intervention, schools will be provided with a
set of recommendations to be implemented in specific
domains, such as increasing physical activity during recess,
improving dietary choices in vending machines and the
cafeteria, and promoting conflict resolution. A health day
will be held in each academic year and will include
participation of teachers, adolescents and families.
Monitoring intervention adherence. Adherence
will be monitored through regular meetings between a
coordinator from the SHE Foundation and the designated
health coordinator, together with the other participating
teachers at the school. These meetings will provide
information about implementation as well as useful
guidance for teachers. In addition, the health coordinator
will prepare an annual report on the school's adherence
to the program curriculum.
Data collection
Timeline and general considerations. The schedule
of enrollment, interventions, and assessments planned in
the SI! Program for Secondary Schools is summarized in
Figure 3, and conforms to SPIRIT 2013 recommenda-
tions.37,38 All participating students will be evaluated at
baseline and at 2 and 4 years thereafter with the same
battery of questionnaires and measurements, unless
otherwise specified. Every effort will be made to follow
up all participants, including those who have changedschool. Assessment of adolescents will include a detailed
assessment of health behaviors and health factors,
including the following: anthropometry and body com-
position; diet (using a food frequency questionnaire that
includes questions to assess polyphenol and carotenoid
intake, as well as polyphenol quantification in saliva and
urine samples); physical activity (including accelerome-
try); smoking and substance abuse; emotion manage-
ment; blood pressure; and blood glucose and lipid
profiles. The assessment at the family and school
environment levels will include surveys and question-
naires. Adolescents' lifestyle behaviors and health will be
assessed through self-reported questionnaires unless
otherwise specified. A trained team of nurses and
nutritionists will guide the adolescents through the
questionnaires, perform measurements, and collect
samples during school hours. Families and school
principals will complete online questionnaires sent by
e-mail via a dedicated data management application. For
families without an e-mail address or internet access,
printed questionnaires will be supplied by regular mail.
Anthropometry and body composition. Body
weight will be measured with an OMRON BF511
electronic scale and height with a Seca 213 portable
stadiometer, with the participant wearing light clothes
and no shoes. Height measurements will be accurate to
0.1 cm and weight to 0.1 kg. Body mass index (BMI) will
be calculated as body weight divided by height squared
(kg/m2). Waist circumference will be measured at the
end of a gentle expiration with a Holtain tape accurate to
0.1 cm. Total fat content will be estimated by bioelectri-
cal impedance analysis with a tetrapolar OMRON BF511
device. A subsample of ~300 control and intervened
adolescents recruited in schools in the Barcelona area will
undergo a DEXA examination using a GE Lunar iDXA
Whole-Body Scanner (GE Healthcare) to obtain accurate
estimates of total body fat, regional fat (android, gynoid,
and visceral), and lean body mass.41 The regions of
Figure 3
STUDY PERIOD
Enroll
ment
Alloc
ation Post-allocation
TIMEPOINT May-June’17
July’
17
Sept-
Oct’17
Oct´17
-
Jan’18
Jan’18-
June’18
Oct’18
-
Feb’1
9
Feb-
May’19
Oct’19
-
Feb’2
1*
Feb-
May’21
ENROLLMENT:
Eligibility screen X
Information meeting X
School recruitment & 
allocation X X
Informed consent from 
participants X
INTERVENTION:
SI! Program, grades 1-2
SI! Program, grades 1-4
ASSESSMENTS:
Student questionnaires  X X X
Student measurements X X X
Parent questionnaire X X X
School environment 
questionnaire X X X
Enrollment, intervention, and assessment schedule in the SI! Program for Secondary Schools. *Oct’19-June’20 and Oct’20-Feb’21.
32 Fernandez-Jimenez et al
American Heart Journal
September 2019interest for regional body composition will be defined
using the software provided by the manufacturer.
Diet.Changes in diet and adherence to theMediterranean
diet among adolescents will be assessed using the validated
Children's Eating Habits Questionnaire - Food Frequency
Questionnaire (CEHQ-FFQ).42-44 This information will be
complemented with a validated 157-item Food Frequency
Questionnaire (FFQ) to be filled out by the families.45
Additional validated shorter questionnaires will be used to
assess attitudes to food.46 We will estimate dietary
polyphenol intake from the 157-item FFQ complemented
with data on the polyphenol content of foods, obtained
from the Phenol-explorer database (http://www.phenol-
explorer.eu/) and other sources.45 With this methodology,
we will obtain individual estimates of the uptake of total
polyphenols and of the different polyphenol classes. As areference method, total phenolics will be estimated in saliva
and urine samples by the Folin–Ciocalteu method, and their
metabolites will be measured by solid-phase extraction and
ultra-high performance liquid chromatography coupled to
mass spectrometry.47 Saliva and urine samples will be
collected at the schools in specific containers and then
aliquoted on-site and transported for storage at −80 °C for
subsequent use. Carotenoid and retinol consumptionwill be
estimated from the 157-item FFQ. Total energy and
micronutrient intake will be estimated using Food Processor
Nutrition and Fitness Software (ESHA Research, Salem, OR).
Physical activity and sedentary habits. To register and
calculate the amount and intensity of physical activity and
sleep patterns, participants will wear an Actigraph wGT3X-
BT accelerometer for 7 consecutive days per evaluation
time-point. To complement this information, participants
Fernandez-Jimenez et al 33
American Heart Journal
Volume 215will complete a diary questionnaire about the type,
intensity, and amount of physical activity per week during
the periods when they are not wearing the accelerometer.
In addition, we will assess selected items from the validated
QAPACE survey for the quantification of individual physical
activity.48 The accelerometer and questionnaire-based
information will be complemented with an assessment of
sedentary habits, based on measures of leisure time spent
with the computer, console, TV, or cell phone.49
Smoking and substance abuse. Attitudes toward
substance abuse will be assessed with a validated
questionnaire.50 An additional questionnaire will be used
to assess self-efficacy,51 participant smoking status,52 and
smoking in the participant's immediate environment.53
Emotion management. A validated questionnaire
will assess self-image perception and profile participants'
body acceptance and the ideals of beauty in this age
group.54 Additional validated questionnaires will evaluate
self-esteem,55 emotional eating,56 and mood57.
Blood pressure. Blood pressure will be measured
with an OMRON M6 monitor. Once the adolescent is
comfortable with the monitor, blood pressure will be
measured 3 times at 2–3 minute intervals according to a
standardized protocol.58
Glucose and lipid profile. Blood glucose, total
cholesterol (TC), high-density lipoprotein (HDL)- and low-
density lipoprotein (LDL)-cholesterol, and triglyceride levels
will bemeasured using the CardioCheck Plus device and PTS-
Panels test strips59 in capillary blood sampled with a lancet.
A brief medical report will be sent to families detailing
the results obtained and making recommendations for
further assessment by their primary physician if needed.
Families and school environment. The question-
naires addressing the families and school environment
were also tested and adjusted during the pilot study.
Parents/caregivers will complete a survey that includes
questions related to sociodemographic parameters (edu-
cation level, occupation, and household income) and
lifestyle parameters (smoking, dietary habits, physical
activity, BMI, and blood pressure). For the evaluation of
the school environment, the school principal will com-
plete a survey containing questions related to recommen-
dations made by the SI! Program. These questions will deal
with the type of foods permitted on the school premises
(including products offered in the cafeteria or vending
machines), measures to promote active commuting to and
from school (walking or cycling) and physical activity
during recess, and conflict resolution.
Definition of health scores
Ideal cardiovascular health. We will use American
Heart Association measures of ideal cardiovascular health
(ICH) in children and adolescents.60,61 Briefly, age- and
sex-adjusted BMI percentiles will be calculated according
to Centers for Disease Control standards,62 with ideal,
intermediate, and poor BMI defined as b85th percentile,85-95th percentile, and N95th percentile, respectively.
The healthy diet score used for dietary profiling will
include thresholds of fruits and vegetables ≥4.5 servings/
day, fish ≥2 servings/week, fiber-rich whole grains ≥1
servings/day, and sugar-sweetened beverages ≤1 L/
week.60,61 Participants who meet all 4 healthy diet
criteria will be classified as having an ideal diet, while
those meeting 2–3 or only 0–1 of the criteria will be
classified as having an intermediate or poor diet,
respectively. Alternatively, fruit and vegetable intake
will serve as a proxy for overall diet in the definition of
ICH, as used in previous studies,63-65 with participants
classified as having an ideal, intermediate, or poor diet if
they report an intake of ≥4.5 servings/day, 2.5–4.4
servings/day, or b2.5 servings/day, respectively.
Physical activity will be primarily categorized according
to accelerometer data, complemented with diary and
questionnaire information.66,67 Ideal physical activity is
defined as ≥60 min/day moderate to vigorous activity,
intermediate activity as any activity b60 min/day, and
poor physical activity as no reported physical activity.
Adolescents who report never tried smoking will be
categorized as having an ideal smoking status; all other
participants will be classified as having a poor smoking status.
Blood pressure percentiles will be calculated according
to blood pressure reference data from the American
Academy of Pediatrics.68 Ideal, intermediate, and poor BP
is defined as b90th percentile, 90-95th percentile,
and N95th percentile, respectively. Ideal total cholesterol
will be TC b170 mg/dL, intermediate TC 170–199 mg/dL,
and poor TC ≥200 mg/dL.60,61 Finally, ideal fasting blood
glucose will be b100 mg/dL, intermediate glucose 100–
125 mg/dL, and poor glucose ≥126 mg/dL.60,61
These 7 cardiovascular health factors and health
behaviors will be classified according to the cardiovas-
cular health score devised by Huffman et al69 and used by
others70 into 3 levels: poor = 0 points; intermediate = 1
point; ideal = 2 points. Based on the total score between
0 and 14 points, participants will be further categorized
into 3 cardiovascular health groups: poor (0–4 points),
intermediate (5–9 points), and ideal (10–14 points).
Additionally, we will use the metrics and criteria for
individual ideal health factors and behaviors to calculate the
ICH score corresponding to the American Heart Association
criteria.71 This score will be calculated by assigning a value
of 1 to each metric meeting the criterion for ideal
cardiovascular health and a value of 0 to metrics not
meeting the criterion. Scores will thus range from 0 to 7,
with a higher score indicating a better cardiovascular health
profile. A low cardiovascular health score will be defined as
≤3 ideal metrics, an intermediate score as 4 or 5 ideal health
metrics, and an ideal score as 6 or 7 ideal health metrics.71
Fuster-BEWAT. We will also use the metrics of the
Fuster-BEWAT health scale.32,72,73 The Fuster-BEWAT
score collects clinical information on lifestyle and risk
factors, including blood pressure (B), exercise/physical
34 Fernandez-Jimenez et al
American Heart Journal
September 2019activity (E), body weight/BMI (W), nutrition/diet regard-
ing fruit and vegetable intake (A), and smoking (T).
Unlike the ICH, the Fuster-BEWAT does not require
laboratory results, making it easier and more suitable for
global use. We will calculate this score in both
adolescents and parents/caregivers participating in the
study. The 5 Fuster-BEWAT components will be divided
into 4 categories ranging from 0 to 3.32,72,73 Similar to
ICH, the Fuster-BEWAT score will be analyzed as a
continuous variable with total score ranging from 0 to 15
points. Additionally, each component will be categorized
as ideal (3) or nonideal (0 to 2), and participants will be
classified as having poor, intermediate, or ideal cardio-
vascular health based on the total number of ideal
components (0 to 1 = poor, 2 to 3 = intermediate, 4 to
5 = ideal).72
Hypothesis and endpoints
The main study hypothesis is that adolescents in the
intervention groups (short-term or long-term) will see an
improvement in health parameters compared with the
control group. The primary study endpoint will be the
change from baseline in the composite ICH score at 2-
year and 4-year follow-up. Secondary endpoints will
include 2-year and 4-year changes from baseline in the
following: ICH subcomponents, the Fuster-BEWAT score,
adiposity markers (waist circumference and body fat
composition), polyphenol and carotenoid intake, emo-
tion management, and family lifestyle and school
environment characteristics. Additional secondary end-
points will include the following: a cross-sectional study
of baseline lifestyle behaviors and health scores among
adolescents and their families; association studies explor-
ing links between adolescent lifestyle behaviors (with
emphasis on dietary components), obesity and other
clinical parameters; an analysis of determinants of the
intervention effect at the school and family levels; a
comparison between the short-term and long-term
educational interventions, and; the exploratory analysis
of the impact of the intervention on parents/caregivers'
health and risk factors.
Statistical methods
Sample size calculation. The sample size and the
number of schools needed to detect a mean difference
between similar-sized control and intervention groups
were calculated with a cluster design using the user-
written command clustersampsi (Stata version 12.0).
Based on the results of the HELENA study,74 we
calculated a minimum sample size of 21 schools (7
schools per study arm) for the detection of a significant
difference of 0.5 absolute points in the ICH score
between groups. In addition to the effect size, other
parameters used for the calculation were as follows: a
significance level of 0.05, statistical power of 80%, 50students per school, a standard deviation in the ICH score
of 1.12, and an intraclass correlation coefficient of 0.05.75
In anticipation of potential loss to follow-up due to the
long study duration, a total of 24 schools (8 schools per
study arm) were included and randomized, correspond-
ing to an expected minimum of ~1200 adolescents
recruited in the study.
Statistical analysis plan. Post-intervention changes
will be evaluated by analyzing data obtained at baseline
and at 2-year and 4-year follow-up. The intervention effect
will be determined as the mean difference in the change
from baseline between the intervention and control
groups by using multilevel linear mixed-effects
models.34,76,77 This methodology will allow us to account
for the hierarchical cluster randomized design of the
study and to adjust for baseline variables. For the primary
endpoint, the dependent variable will be the defined
overall ICH score for adolescents. A priori fixed effects in
each model will be the corresponding baseline score and
treatment group. Schools will be handled as random
effect. Interaction models will be run to identify potential
age-by-treatment or sex-by-treatment effects for the main
outcome variable, as well as to study the influence of
other variables on the overall results at the adolescent,
family, and school environment levels. The same mixed-
linear models strategy will be used to evaluate secondary
outcomes. Using a similar approach, multilevel logistic
and ordered logistic mixed-effects models will be used for
the analysis of categorical data. Both intention-to-treat and
per protocol analyses will be performed.
The SI! Program for Secondary Schools is a randomized
trial consisting of repeated measurements of variables
related to lifestyle behaviors and health. This design
allows simultaneous testing of different hypotheses; for
each hypothesis, the investigators will draft a specific
statistical analysis plan and select the appropriate data
treatment and models to study associations and consider
potential confounders. Cross-sectional associations be-
tween independent variables and outcomes of interest
will be analyzed using multivariate linear regression
models for continuous variables and logistic regression
models for categorical variables. The adjustment variables
will be defined a priori, depending on the research
question, and will be entered into the model upon
combination of the clinical and statistical criteria.
All statistical analyses will be performed using Stata
version 12.0 or superior (StataCorp, College Station,
Texas, USA) or a similar available statistical software
program.Discussion
The SI! Program for Health Promotion in Secondary
Schools seeks to provide evidence that a multilevel,
multicomponent school-based educational intervention
can induce long-lasting changes toward a healthy lifestyle
Fernandez-Jimenez et al 35
American Heart Journal
Volume 215among adolescents. Our ultimate goal is to provide
effective health promotion strategies for young people,
thus helping to combat the alarming increase in risk
factors contributing to the CVD epidemic. Schools and
their students will be randomized to a long-term or short-
term intervention or to a control arm. The schools
allocated to the short-term intervention group will run
the educational program students during their first 2
years of secondary school, coinciding with the age range
from 12 to 14 years, the critical period for the initiation of
unhealthy behaviors.52,78 A demonstration of similar
beneficial effects with the shorter and longer interven-
tions would facilitate scale-up of the educational pro-
gram. The study will additionally provide a
comprehensive characterization of lifestyle behaviors
and health in a large sample of adolescents in Spain and
will explore the association between these lifestyle
behaviors. This analysis will have a particular focus on
dietary components and patterns, including examination
of obesity and other clinical parameters though detailed
assessment of habits and analysis of biological samples.
The magnitude of the problem: current lifestyle
behavior and health trends in adolescents
The global prevalence of ideal health behaviors and
health factors among adolescents is low.6,71,79,80 Of
particular concern is the low proportion of individuals
having an ideal status for the diet and physical activity
components, reflected in alarming rates of overweight
and obesity in this age group. According to recent
estimates, 1 in 3 adolescents in Spain are overweight or
obese,19 and similarly worrying rates are reported
worldwide.6,9,80 This problem is predicted to have a
highly negative societal impact because obesity is
strongly linked to mortality and multiple comorbidities,
mainly related to early CVD.81 Our study will comple-
ment available data by providing a cross-sectional in-
depth analysis of the lifestyle behaviors and health in one
of the largest samples of adolescents examined to date in
Spain.
A new paradigm: from primary prevention to primor-
dial prevention and health promotion
Clinical practice in asymptomatic populations has
focused on primary prevention through the modification
of already present cardiovascular risk factors.82 While this
approach is undoubtedly positive, it does not go far
enough. To achieve optimal cardiovascular health and
minimize the risk of long term CVD, programs are needed
to prevent the development of risk factors through
lifestyle changes starting in early childhood (primordial
prevention).15,83 Likewise, the accumulation of obesity
and other risk factors during the transition to adulthood
leads to higher rates of adverse outcomes.9,13,18 Reduc-
tion of these risk factors, even in children enteringadolescence with low cardiovascular health, has been
shown to be beneficial.13,84 Prevention strategies focused
on promoting and maintaining a healthy lifestyle in
children and adolescents, and that can continue into
adulthood,85 are likely to have a decisive influence on
long-term health and justify intervention efforts at early
stages.86,87 On this basis, we will test the hypothesis that
a health promotion intervention targeting adolescents
will induce long-lasting beneficial changes in relevant
health behaviors and health factors.
School-based interventions for health promotion in
adolescents
Although there have been many studies of school-based
interventions, few were validated in randomized trials
targeting adolescents.23-25 Furthermore, most studies
focused on a single lifestyle component such as diet or
physical activity through structured diet or exercise
interventions and targeted weight loss rather than overall
health promotion. Systematic reviews suggest mild
effectiveness of school-based interventions in preventing
adolescent obesity; however, this analysis is limited by
heterogeneity of interventions, variable design quality,
and lack of longer-term follow-up.23-25 Moreover, two
recent large school-based cluster-randomized controlled
trials showed no evidence of an intervention effect on
behavioral or weight outcomes at long-term follow-up,88-
90 suggesting that effective interventions may require
upstream intervention at the family, school environment,
and societal levels.
The SI! Program: a holistic school-based health
promotion intervention for the young
The SI! Program has been designed to promote long-
lasting healthy lifestyle behaviors and cardiovascular
health through the implementation of innovative evi-
dence-based multilevel and multicomponent educational
strategies from early childhood to adolescence.91 The
educational program includes not only the participating
children and adolescents but also key elements of their
immediate environment, including family and the school
environment. The program content is adapted to each
educational stage according to the transtheoretical model
of sequential behavior change (Knowledge to Attitudes to
Habits),31 and aims to empower the individual toward
healthy living.32-35,76,92,93 Thus, among preschoolers (3 to
5 year-olds), the aim is to promote enjoyable knowledge
acquisition about healthy eating and exercise through the
use of storybooks, coloring kits, and emotion cards
featuring characters from Sesame Street and Cardio (the
SI! Program mascot).93 Children respond positively to
this curriculum because they enjoy it and identify with
the characters.94 Later, children beginning their Elemen-
tary schooling (at the age of 6) begin to develop their
attitudes and abilities to make conscious choices, and
36 Fernandez-Jimenez et al
American Heart Journal
September 2019become less dependent on external factors. Parents/
caregivers and teachers are still crucial to providing
support and encouragement to children, including access
to healthy food and opportunities for physically activi-
ty.95 Finally, in the adolescence, individuals begin to
exercise their independence from parental monitoring,
formulating their own judgements and decisions about
lifestyle habits that will eventually continue into adult-
hood.96 Adolescence also marks the stage of rapid
physical development when tangled notions of appear-
ance and perceptions become especially important as
adolescents develop self-esteem and self-conceptions of
body image, which can be both consequence and cause
of changes in diet and exercise patterns in this phase.97 In
a health promotion intervention during adolescence,
emotion management is a crucial cohesive component
for enhancing the uptake of healthy behaviors and self-
steam and instilling protective behavioral mechanisms
against substance abuse. In parallel, adolescents can be
effectively engaged in learning about healthy lifestyles
through gamification strategies.98,99 In summary, our
health promotion intervention relies on the potential of
the adolescent to have a positive impact on their own
health that will be reinforced by the family and school
environment.
Exploring the intersection between diet and obesity in
adolescents
The Mediterranean diet is a healthy eating pattern
culturally rooted in the countries of the Mediterranean
basin; however, there is an increasing prevalence of poor
adherence to the Mediterranean diet among young
people in Spain,100 and food consumption patterns
among adolescents are increasingly characterized by a
low intake of fruits and vegetables and a high intake of
foods high in saturated fat, sugar, and salt.101 These
dietary patterns are independently associated with
adiposity,102 low cardiorespiratory fitness, and poor
cardiovascular health profiles.103 In contrast, adherence
to the Mediterranean diet is related to lower obesity rates
than found in individuals with low adherence across their
life span.104,105 Furthermore, the Mediterranean diet has
been shown to be effective in reducing CVD106 and other
chronic diseases.107
In addition to changes in food choices and macronu-
trients, adherents to a Mediterranean diet have a
significantly increased intake of several bioactive com-
pounds, including polyphenols and carotenoids.106
Polyphenols are naturally distributed in plant-derived
foods such as vegetables, fruits, seeds, coffee, wine, and
tea.108 Epidemiological studies and meta-analyses strong-
ly suggest that dietary polyphenols offer protection
against CVD, diabetes, osteoporosis, cancer, and neuro-
degenerative diseases; however, data on the potential
efficacy of polyphenols to modulate obesity in humans
are limited and inconsistent.109 Only a few human studieshave reported a relationship between polyphenol intake
and protection against obesity, suggesting that these
compounds could reduce body weight through different
mechanisms,110 including the upregulation of energy
expenditure.111 Carotenoids comprise a group of lipo-
philic pigments produced by plants and certain photo-
synthetic microorganisms and are responsible for the red,
yellow, and orange coloration of fruits, vegetables, and
some animal tissues.112 One of the main known functions
of carotenoids in the human diet is to serve as precursor
of vitamin A, which plays an important physiological
role.113 Carotenoid consumption has been linked to a
reduced risk of several chronic diseases, including CVD,
age-related macular degeneration, and some types of
cancer.114-117 An emerging perspective on the function of
carotenoids and carotenoid-derived products such as
retinoids suggests a connection between these com-
pounds and the control of body fat accumulation; this
interaction involves the modulation of adipocyte biology
and body adiposity through several mechanisms and has
implications for the management of obesity and obesity-
related metabolic disturbances.118-120
By studying the impact of the intake of key nutrients on
adiposity and other health parameters, our study may
help to explain the beneficial impact of specific dietary
components and patterns on adolescent health.
Limitations and strengths
The major limitation of the trial is its long duration;
however, this can also be seen as a strength. Another
limitation is the regular changeover in school boards,
which usually takes place every 4 years, introducing the
possibility of changing priorities. Likewise, teacher
mobility in Spain is high and could require re-initiation
of the training and familiarization process. In addition,
families may move home during the study period,
resulting in study dropouts. To minimize the impact of
this issue, the sample size calculation accounted for
potential loss to follow-up and dropouts, and we will
perform an intention-to-treat analysis. Because the
included population consists of adolescents, the out-
come/endpoint does not include clinical events. Howev-
er, as mentioned, CVD has its origins during childhood
and adolescence; therefore, primordial prevention strat-
egies promoting healthy behaviors in childhood and
ado l e scence a re to be espec i a l l y encour -
aged.12,15,60,82,91,121 These limitations will to some
degree be obviated by the implementation of strategies
allowing us to follow up participants beyond the end of
the study period.
The study also has significant strengths. This cluster-
randomized controlled trial will include a large sample of
adolescents in Spain and a detailed assessment of health
behaviors and health factors. The educational interven-
tion is supported by several unique features, including
the accessibility of materials on the SI! Program website,
Fernandez-Jimenez et al 37
American Heart Journal
Volume 215the projected low relative cost of a large-scale implemen-
tation, the inclusion of emotional management as a major
behavioral component, and the implementation of the
program by the adolescents' own teachers. The SI!
Program is flexible and can easily be adapted to different
countries, income settings, languages, and children's
cognitive functional level.32-35 These characteristics
make the SI! Program educational intervention highly
suitable for worldwide implementation and offer the
potential to curtail the current CVD epidemic through the
promotion of healthier behaviors and lifestyles.
Ethics approval and consent to partici-
pate
The study was approved by the Committee for Ethical
Research (CEI) of the Instituto de Salud Carlos III in
Madrid (CEI PI 35_2016), the CEI of the Fundació Unió
Catalana d'Hospitals (CEI 16/41), and the Bioethics
Commit tee of the Univer s i t y o f Barce lona
(IRB00003099). Informed consent forms are provided
to the teachers, who distribute them to parents, collect
the completed forms, and return them to the research
team. Participating parents/caregivers, adolescents and
school boards have the right to withdraw from the study
at any time. Data will be collected and handled according
to Spanish Law 15/1999 on the Protection of Personal
Data, and updated to the EU General Data Protection
Regulation 2016/679, ensuring the confidentiality of all
participants' data. The study is registered in ClinicalTrials.
gov, number NCT03504059. The reporting of this study
protocol adheres to the SPIRIT guidelines.37,38
Availability of data and material
The data and materials presented and referred to in
publications can be requested from the principal
investigators.
Disclosure
None.
Author contributions
VF conceived the overall study. RF-J, GS-B, AT-R, PB,
MdM, BI, CS, MD, RE, JF-A, and RL-R made substantial
conceptual contributions to the overall study design and
coordination, and drafted proposals for obtaining com-
petitive funding. GS-B, AT-R, PB, MdM, VC, DH, CS, MD,
RE, JF-A, and RL-R coordinated recruitment of schools and
participants, the consent process, and/or data collection.
CR, VC, XO, DH, and IC contributed to the study design
and coordinated the development and implementation of
the educational program. AdC generated the allocation
sequence and assisted with data management and
statistical methodology. RF-J drafted the first version ofthe manuscript along with GS-B, RE, JF-A, and RL-R. All
authors revised the manuscript critically for intellectual
content and approved the published version.Acknowledgements
The authors thank the SHE Foundation (intellectual
owner of the SI! Program) and its collaborators: Ramona
Martínez, Emilia Gómez-Pardo, Yolanda Sánchez, Mi
Querido Watson, Fontventa and the Gasol Foundation.
We would like to thank the working group of “Programa
de salut a l'ESO”, coordinated by the Department of
Education of the Generalitat de Catalunya (Spain). We
especially thank adolescents and their families, teachers,
and schools participating in the study. Simon Bartlett
(CNIC) provided English editing.
Appendix. Supplementary data
Supplementary data to this article can be found online
at https://doi.org/10.1016/j.ahj.2019.03.014.References
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