Healthy Mothers-Healthy Children: An Intervention With Hispanic Mothers and Their Young Children
Phase: NA
Conditions: Overweight and Obesity, Adiposity, Nutrient; Excess, Physical Activity
Sponsor: University of Miami

Healthy Mothers-Healthy Children 
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Revision History of this Protocol Template: 
Version Information 
Summary of Revisions Made 
Rationale 
Version 2.0 – Approved by 
Principal Investigator, Co-
Investigators and Consultants 
Expanded ages of children to 3 to 5 
years old  
To increase the study sample 

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Healthy Mothers-Healthy Children 
Protocol Number:  
National Clinical Trial (NCT) Identified Number: NCT03866902 (March 7, 2019) 
Principal Investigator: Dr. Hudson Santos 
Sponsor: The National Institute of Nursing Research 
Grant Title: Healthy Mothers – Healthy Children: An Intervention with Hispanic 
Mothers and their Young Children  
Grant Number: 1R01NR017199-01 
Funded by: The National Institute of Nursing Research 
Version Number: 2 
2019-06-19 

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Summary of Changes from Previous Version: 
 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Sample 
Changed age of children from 4 year 
old to 3 to 5 year olds 
To increase sample age range 
 
 
 

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CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein will be published or 
disclosed without prior approval of the Principal Investigator or other participating study leadership 
and as consistent with the NIH terms of award.  
 

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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 3 
1.3 
Schedule of Activities .......................................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Rationale .................................................................................................................................... 6 
2.2 
Background........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 7 
2.3.1 
Known Potential Risks ..................................................................................................... 7 
2.3.2 
Known Potential Benefits .............................................................................................. 10 
2.3.3 
Assessment of Potential Risks and Benefits .............................................................. 11 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 11 
4 
STUDY DESIGN ........................................................................................................................................... 12 
4.1 
Overall Design .................................................................................................................................... 12 
4.2 
Scientific Rationale for Study Design.............................................................................................. 12 
4.3 
Justification for Intervention ............................................................................................................. 12 
4.4 
End-of-Study Definition ..................................................................................................................... 12 
5 
STUDY POPULATION ................................................................................................................................ 13 
5.1 
Inclusion Criteria ................................................................................................................................ 13 
5.2 
Exclusion Criteria ............................................................................................................................... 13 
5.3 
Lifestyle Considerations .................................................................................................................... 14 
5.4 
Screen Failures .................................................................................................................................. 14 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 14 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 15 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 15 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 15 
6.1.2 
Administration and/or Dosing ....................................................................................... 17 
6.2 
Fidelity ................................................................................................................................................. 17 
6.2.1 
Interventionist Training and Tracking .......................................................................... 17 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 17 
6.4 
Study Intervention/Experimental Manipulation Adherence.......................................................... 17 
6.5 
Concomitant Therapy ........................................................................................................................ 17 
6.5.1 
Rescue Therapy ............................................................................................................. 18 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 18 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 18 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 18 
7.3 
Lost to Follow-Up ............................................................................................................................... 18 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 18 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 19 
8.2 
Safety Assessments .......................................................................................................................... 19 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 19 
8.3.1 
Definition of Adverse Events ........................................................................................ 19 

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8.3.2 
Definition of Serious Adverse Events .......................................................................... 19 
8.3.3 
Classification of an Adverse Event .............................................................................. 19 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 25 
8.3.5 
Adverse Event Reporting .............................................................................................. 25 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 26 
8.3.7 
Reporting Events to Participants ................................................................................. 26 
8.3.8 
Events of Special Interest ............................................................................................. 26 
8.3.9 
Reporting of Pregnancy ................................................................................................ 26 
8.4 
Unanticipated Problems .................................................................................................................... 26 
8.4.1 
Definition of Unanticipated Problems .......................................................................... 26 
8.4.2 
Unanticipated Problems Reporting .............................................................................. 26 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 26 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 26 
9.1 
Statistical Hypotheses ....................................................................................................................... 26 
9.2 
Sample Size Determination .............................................................................................................. 27 
9.3 
Populations for Analyses .................................................................................................................. 28 
9.4 
Statistical Analyses............................................................................................................................ 28 
9.4.1 
General Approach .......................................................................................................... 28 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 28 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 28 
9.4.4 
Safety Analyses .............................................................................................................. 28 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 28 
9.4.6 
Planned Interim Analyses ............................................................................................. 28 
9.4.7 
Sub-Group Analyses ..................................................................................................... 28 
9.4.8 
Tabulation of Individual Participant Data .................................................................... 28 
9.4.9 
Exploratory Analyses ..................................................................................................... 28 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 29 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 29 
10.1.1 
Informed Consent Process ........................................................................................... 29 
10.1.2 
Study Discontinuation and Closure ............................................................................. 30 
10.1.3 
Confidentiality and Privacy ........................................................................................... 30 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 31 
10.1.5 
Key Roles and Study Governance .............................................................................. 31 
10.1.6 
Safety Oversight ............................................................................................................. 31 
10.1.7 
Clinical Monitoring .......................................................................................................... 31 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 31 
10.1.9 
Data Handling and Record Keeping ............................................................................ 32 
10.1.10 
Protocol Deviations ........................................................................................................ 33 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 33 
10.1.12 
Conflict of Interest Policy .............................................................................................. 33 
10.2 
Additional Considerations ................................................................................................................. 33 
10.3 
Abbreviations and Special Terms ................................................................................................... 33 
10.4 
Protocol Amendment History ........................................................................................................... 35 
11 
REFERENCES ............................................................................................................................................. 36 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for 
the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) must 
be obtained before any participant is consented. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form(s) 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances that this 
study will be conducted according to all stipulations of the protocol, including all statements regarding 
confidentiality, and according to local legal and regulatory requirements and applicable US federal regulations 
and ICH guidelines. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
2019-06-19 
 
Name: Dr. Hudson Santos 
 
Title: 
Principal Investigator 
 
Investigator Contact Information 
Affiliation: The University of North Carolina at Chapel Hill School of Nursing 
Address: Campus Box 7460 
Telephone: 919-259-4812 
Email: hsantosj@email.unc.edu 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title: 
Healthy Mothers-Healthy Children: An Intervention with Hispanic 
Mothers and their Young Children 
Grant Number: 
1R01NR017199-01 
Study Description: 
This study will use a two-group randomized repeated measures 
study design to evaluate the efficacy of the intervention with 294 
dyads of overweight or obese Hispanic mothers and their 3-5 year 
old children.  
Objectives: 
Primary Objectives: Adiposity and weight in mothers and children 
from Time 1 (baseline) to Time 2 (9 months) and Time 3 (15 
months).  
Secondary Objectives: Health behaviors in mothers and children 
from Time 1 (baseline) to Time 2 (9 months) and Time 3 (15 
months).  
Endpoints: 
Primary Endpoint: Adiposity and weight in mothers and children 
from Time 1 (baseline) to Time 2 (9 months) and Time 3 (15 
months).  
Secondary Endpoints: Health behaviors in mothers and children 
from Time 1 (baseline) to Time 2 (9 months) and Time 3 (15 
months). 
Study Population: 
A total of 294 Hispanic mothers and 294 Hispanic 3-5 year old 
children from two counties in North Carolina.   
Phase or Stage: 
Randomized controlled trial with an experimental and equal 
attention control group.  
Description of 
Sites/Facilities Enrolling 
Participants: 
Two public health departments and two community health centers 
in two counties in North Carolina.  
A total of 294 mothers and their 294 children ages 3-5 years old.  
Description of Study 
Intervention/Experimental 
Manipulation: 
An experimental group of women receive a nutrition, exercise and 
coping skills training and physical activity intervention. An 
experimental group of children receive Color Me Healthy classes. 
An equal attention control group women receive English for Second 
Language classes and the children have books read to them and 
they color with crayons.  
Study Duration: 
A total of 5 years or 60 months.  
Participant Duration: 
Each participant will be in the study a total of 15 months.  
 
 
 
 
 
 
 
 
 
1.2 
SCHEMA  

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Flow Diagram 
 
Pre-Screening 
 
 
 
 
Visit 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total N: 294 mother child dyads 
Pre-screen potential participants by inclusion and exclusion criteria 
Conduct informed consent process. Perform baseline assessments. 
Final Assessment at 15 months 
Arm 2 
N = 147 
Arm 1 
N = 147 
Administer study intervention and equal attention control group sessions 1-12 weekly 
Randomize 
Administer study intervention and equal attention control group sessions 13-18 monthly 
Post-Intervention assessment at 9 months 

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1.3 
SCHEDULE OF ACTIVITIES  
 
Variables and Their Measurement 
Respondent 
Time 1 
Time 2 
Time 3 
Short Acculturation Questionnaire for Hispanics 
Mother 
X 
 
 
Health History Questionnaire 
Mother 
X 
 
 
Sports Physical  
Mother  
X 
 
 
Adiposity (Primary Outcomes) 
 
 
 
 
   Waist Circumference 
Mother/Child 
X 
X 
X 
   Triceps and Subscapular Skinfolds 
Mother/Child 
X 
X 
X 
Weight Status (Primary Outcomes) 
 
 
 
 
   Height/Weight 
Mother/Child 
X 
X 
X 
   BMI/BMI Percentile 
Mother/Child 
X 
X 
X 
Health Behavior  
 
 
 
 
   Adult Health Behavior Survey 
Mother 
X 
X 
X 
   Health Promoting Lifestyle Profile II 
Mother 
X 
X 
X 
   24-hour Food Recall for 3 days 
Mother for Self/Child 
X 
X 
X 
   Accelerometer for 7 days 
Mother for Self/Child 
X 
X 
X 
Self-Efficacy  
 
 
 
 
   Eating Self-Efficacy Scale 
Mother 
X 
X 
X 
   Exercise Self-Efficacy Scale 
Mother 
X 
X 
X 
Demographic Data 
Mother for Self/Child 
X 
 
 
Health History Update Questionnaire 
Mother for Self/ Child 
 
X 
X 
Process Evaluation Bi-Monthly 
Project Manager 
 
 
 
Exit Interviews 
Mother 
 
 
X 
Time 1 (0 months [baseline]) 
Time 2 (9 months [completion of the intervention]) 
Time 3 (15 months [after 6 months with no contact from the study staff]) 
 
 

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INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Background: Hispanic women and children who become overweight or obese are at risk for developing 
prediabetes, type 2 diabetes, and cardiovascular disease later in life. Interdisciplinary interventions which 
target Hispanic women and their 3-5-year old children to improve nutrition and physical activity behaviors, 
manage adiposity and weight in mothers, and prevent excessive adiposity and weight gain trajectory in their 
children offer promise to break the intergenerational cycle.  
Methods: Using a randomized two-group, repeated measures experimental design, the goal of the proposed 
study is to investigate the efficacy of a 12-week nutrition and physical activity program including education, 
coping skills training, and home-based intervention in Hispanic women and their 3-5-year old children. The 
program includes 6 months of continued monthly contact to help overweight and obese Hispanic mothers and 
their children improve adiposity, weight (trajectory for children), health behaviors (nutrition and physical 
activity), and self-efficacy We will partner with two federally qualified health departments in Durham and 
Chatham counties, North Carolina to enroll participants. We will partner with community centers to deliver the 
intervention. A total of 294 Hispanic women with a BMI>25 kg/m2 and 294 Hispanic 3-5-year old children with a 
>25th BMI percentile will be enrolled over 4 years and randomized to the experimental or equal attention control 
group. Data will be collected at Time 1 (0 months [baseline]) to Time 2 (9 months [completion of the 
intervention]) and Time 1 to Time 3 (15 months [after 6 months with no contact from the study staff]). Data 
collected will include adiposity in mothers and children and weight (primary outcomes: BMI in mothers and BMI 
percentile in the children). Secondary outcomes will include health behaviors and self-efficacy in the mothers 
and in the children. We will also evaluate the cost of delivering the program for public health departments. We 
will use general linear mixed models to test the hypotheses.  
Discussion: Decreasing overweight and obesity in Hispanic women and slowing adiposity and weight gain 
trajectory in young Hispanic children is urgently needed to decrease morbidity, mortality, and future health care 
costs.  
2.2 
BACKGROUND  
 
There is an urgent need to prevent excessive adiposity and weight gain trajectory in Hispanic children. 
Overweight (BMI > 85th and < 95th percentile) and obesity (> 95th percentile) are prevalent in both genders, 
affect all ages, and cross all ethnic groups, though minority children from families with lower incomes and less 
education are particularly high-risk [1]. The prevalence of overweight and obesity in 2-to-19 year old Hispanic 
youth is 38.9%, non-Hispanic Black youth is 35.2%, and non-Hispanic White youth is 28.5% [1]. Obesity 
increases risk for developing prediabetes, type 2 diabetes and cardiovascular disease [2, 3]. Childhood obesity 
is estimated to cost $14 billion annually in direct medical costs in the United States (U.S.) [4, 5].  
 
There are currently 55.3 million Hispanics living in the U.S. [6]. In 2014, Hispanics accounted for 9% of the 
population in N.C. [6]. Overweight and obesity in Hispanic mothers and their children involve a complex 
interplay between acculturation, the food environment, the built environment, the influence of media, and a lack 
of support [7]. Many Hispanic men work long hours, while mothers stay home to care for their children without 
close family support [7]. Greater acculturation is significantly associated with increased consumption of fast 
foods and decreased moderate-to-high intensity exercise [8, 9]. Many communities where Hispanics live lack 
access to healthy affordable food and have only one-third as many supermarkets as other communities [10]. 
Confronted with an abundance of low cost, calorie-dense, high fat food, and limited access to fresh produce. 
Hispanics increase their intake of calories and fat and decrease their intake of fruits and vegetables [7, 11].  

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Transportation, infrastructure, and safety issues limit Hispanic mothers’ and children’s options for physical 
activity. Mothers engage in less physical activity than in their home country where most did not own cars, 
televisions, or computers and they were more likely to include physical activity in their everyday life [7, 11]. 
Hispanic parents also report barriers to their children’s physical activity [12], including neighborhood safety and 
transportation problems [12]. Hispanic children (25.9%) are less likely than non-Hispanic White children 
(46.6%) to be involved in organized physical activity outside of school [12]. The media also contributes to the 
lack of healthy eating and physical activity. In 2015, advertisers spent more than $7.8 billion on restaurant, 
food, and beverage advertising targeting Hispanic households [13]. Hispanic children spend more time 
watching television than non-Hispanic White children (321 minutes per day versus 216 minutes) [14], and the 
number of hours spent watching television is positively associated with overweight and obesity [15, 16].  
 
Mothers influence children’s nutrition and physical activity behaviors by modeling health behaviors, structuring 
children’s activities, and selecting content and portion sizes of meals [17-20]. Mothers have more influence 
when children are in the preschool stage than in later stages of development [21]. Four year olds are able to 
pay attention to activities, think in logical steps, have good language skills, run, jump, skip, and socially and 
emotionally they start to share, cooperate and take turns [22]. We propose to teach mothers strategies to 
improve their own nutrition and physical activity behaviors, build their self-efficacy, and learn how to help their 
children eat healthier and increase physical activity. We will focus on 3-5-year-olds because our pilot work 
indicates that they are developmentally more prepared for intervention than younger children [23]. 
 
Nutrition and physical activity programs used in the general population that were found to be most effective 
incorporated both behavioral and cognitive strategies and included parental involvement [19, 24, 25]. To date, 
we have found no interventions that have been developed to help overweight or obese Hispanic mothers 
manage their weight and prevent excessive adiposity and weight gain trajectory in their young children using a 
culturally and language tailored intervention. We propose to test the efficacy of a nutrition and physical activity 
education, coping skills training, and physical activity intervention (Healthy Mothers-Healthy Children 
Intervention) tailored to Hispanic mothers and using an age-appropriate nutrition and physical activity 
intervention for their 3-5-year-old children (Color Me Healthy) [26]. Coping skills training includes social 
problem solving, cognitive restructuring, assertiveness training and conflict resolution to improve self-efficacy 
[27-31]. We will provide support as mothers they increase their self-efficacy and practice new nutrition and 
physical activity behaviors and help their children eat healthier and increase physical activity.  
 
2.3 
RISK/BENEFIT ASSESSMENT  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Risks to Human Subjects 
 
Human Subjects Involvement, Characteristics, and Design 
 
Institutional Review Board (IRB) approval was obtained from The University of North Carolina at 
Chapel Hill (UNC-CH). Using a randomized two-group, repeated measures experimental design, the goal of 
the proposed study is to investigate the efficacy of a 12-week nutrition and exercise education, physical 
activity, coping skills training, and home-based exercise intervention in Hispanic women and their 3-5-year old 
children and 6 months of continued monthly contact to help overweight and obese Hispanic mothers improve 
adiposity, weight, health behaviors and self-efficacy and their 3-5-year old children improve their adiposity and 
weight gain trajectory. We will partner with two federally qualified health departments in two North Carolina 

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counties to enroll Hispanic women and their 3-5-year old children and we will partner with community centers 
to deliver the intervention. 
 
Inclusion criteria for mothers will be age 18 years or older; self-identification as Hispanic heritage; limited 
English proficiency and little acculturation, as measured by the Short Acculturation Scale for Hispanics with a 
score from 1.00 to 2.99; ability to understand spoken Spanish; a BMI >25kg/m2; residence with the child; 
consent to join the study and consent for their child to join the study. Inclusion criteria for children will be age 3-
5-years; ability to understand spoken Spanish; a BMI > 25th percentile for age and gender; and mother’s 
consent for them to join the study. Health care providers will not be asked to give permission for either mothers 
or children to join the study. Mothers will fill out a health history questionnaire to ascertain if they have a heart 
murmur, congenital heart disease, family history of sudden death, difficulty walking or exercising or history of 
psychological problems that would prevent participation in group classes. A sports physical will be conducted 
by a bilingual nurse practitioner on all mothers during baseline data collection to ensure that they have no 
medical problems that would prohibit physical activity. If a mother answers yes to any of these health history 
questions or the nurse practitioner finds a heart murmur or any other concerns, she will be excluded from the 
study and referred to a health care provider. Dyads will be enrolled in eight cohorts over four years. Each 
cohort will be enrolled over a 1-month period. We have not included fathers, as in previous studies in this 
population we have learned the majority of these fathers work 6 days a week and do not have the time to 
attend class with their child. After enrollment and baseline assessment, dyads will be randomized to either the 
intervention or control group using a computer-generated randomization table, stratifying by BMI group, 
overweight (<30 kg/m2) and obese (>30kg/m2), and utilizing blocking to help ensure balance between the 
groups. Mothers will be informed of their group assignment by telephone. 
 
Data will be collected at Time 1 (Baseline [0 months]), Time 2 (Post Intensive Intervention and 
Continued Support [9 months]), and Time 3 (6-Months after Completion of Continued Support [15 months]). 
Data collected will include adiposity (primary outcome) in mothers and children (waist circumference, triceps 
and subscapular skinfolds), weight status (primary outcome) in the mothers (body mass index [BMI]) and 
BMI percentile in the children, health behaviors in the mothers (Adult Health Behavior Questionnaire, 
Lifestyle Health Promoting Profile II, 3 day 23-5-Hour Food Recall, and 7 day Accelerometer) and in the 
children (3 day 24-Hour Food Recall and 7 day Accelerometer). Self-Efficacy in the mothers (Eating Self- 
Efficacy Scale and Exercise Self-Efficacy Scale) will also be measured. We will also evaluate the cost of 
delivering the program for public health departments. Data analysis will use general linear mixed models to test 
the hypotheses. Both intervention and control group mothers will each receive $50 after each data collection 
and $5 each time they come to class or data collection to help with transportation costs. 
 
The mothers in the Healthy Mothers-Healthy Children Intervention group will receive a 12 week Intensive 
Intervention and 6 months of Continued Support. The Intensive Intervention will include 60 minutes of nutrition 
and exercise education and coping skills training and a 45 minute physical activity class and a home-based 
physical activity program each week for 12 weeks. The Continued Support classes for the mothers in the 
intervention group will include 60 minutes of classroom discussion regarding problems they are having with 
nutrition and physical activity for themselves and their children and a 45 minute physical activity class monthly 
for 6 months. The children in the intervention group will receive an Intensive Intervention (105 minutes total), 
which will include 60 minutes of Color Me Healthy classes and 45 minutes of free play weekly for 12 weeks. 
The Continued Support classes for the intervention children will include a review of the Color Me Healthy 
classes and 45 minutes of free play monthly for 6 months. Each weekly or monthly class for mothers and 
children is a total of 105 minutes. 
 
The equal attention control group mothers will receive English as a Second Language (ESL) classes for 
105 minutes for 12 weekly classes and then monthly classes for 6 more months. The equal attention control 
group mothers will receive homework assignments to help them practice their English language skills. The 
homework handouts will be at the same frequency as the Healthy Mothers-Healthy Children Intervention group 

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mothers. The equal attention control group children will receive 105 minutes of free play for 12 weekly classes 
and then 6 monthly free play classes. 
 
Participants will be tracked using ID numbers. All data will be double entered by different RAs into a 
SAS database with built-in range checks and skip patterns. Comparisons will be run on the two versions, and 
inconsistencies will be checked against the raw data and corrected. Data will be verified and stored in a secure 
server. Data will undergo range, consistency, and outlier checks. All data decisions will be recorded in a 
logbook with an audit trail. SAS datasets will be created for analysis. 
 
Risks to Human Subjects 
 
The intervention requires that during the Intensive Intervention each intervention woman and child attend 12 
classes for 60 minutes. During Continued Support women and children will meet monthly for 6 months with 
their interventionists. The interventionist will weigh all women in a private area and provide feedback. The 
interventionist will then meet with the women for 60 minutes to discuss nutrition and exercise challenges. The 
women will then attend a 45 minute exercise session. The women will also be encouraged to exercise 30 to 60 
minutes a day on most days of the week. The equal attention control group women and children will receive an 
equal number of days and minutes to meet, however the mothers will receive English as Second Language 
classes and the children will receive free play. 
 
As a part of the first data collection after the mothers consent for themselves and their child, the mothers will fill 
out data. A health history and sports physical will be conducted on all mothers during the baseline data 
collection to ensure there are no medical problems before engaging in physical activity. The mothers will also 
fill out a health history for their child. The sports physical will be conducted by a bilingual nurse practitioner 
hired for the study with experience in conducting sports physicals and medical clearance in a private room. At 
the data collection, the women will have their height, weight, waist circumference, triceps and subscapular 
skinfolds measured by a bilingual research assistant in a private room. Children will have their height, weight, 
waist circumference, triceps and subscapular skinfolds measured by a bilingual research assistant in a private 
room with their mother present. We are aware that adverse events may occur and an adverse event monitoring 
committee will monitor their occurrence and the overall risk of the study to both mothers and their children. 
Women who express fatigue during sessions will be excused from the session and another time convenient for 
them will be scheduled to make up the content. If a woman expresses fatigue during data collection, the data 
collection session will be terminated immediately, and a follow-up appointment scheduled. No adults 
expressed fatigue in Dr. Santos’s previous studies. It is not anticipated that the classes or data collection will 
cause any adverse effects, but participants will be encouraged to identify any concerns to the study staff. 
Identifying data will be kept separate from questionnaires and locked in the PI’s filing cabinets and locked 
office. All adult and child participants will continue to receive routine medical care from their health care 
providers throughout the study. Referral to their health care provider will be made if any adverse effects are 
self-identified There are no known social or legal risks for the women who consent to participate for themselves 
and consent for their children in this study. 
 
Adequacy of Protection against Risks 
 
We will hire only bilingual staff, and all recruitment and intervention materials and instruments will be in 
Spanish. Two months before enrollment, the bilingual project manager will give a presentation to staff at both 
public health departments and place Spanish language posters and brochures in each waiting room. 
The posters and brochures will describe the benefits of good nutrition and physical activity and state the 
eligibility criteria for study participation. We will also put ads in local Spanish language newspapers and 
announcements on the local Spanish language radio station with our toll free number. Bilingual RAs will be 
available in the waiting rooms on clinic days to share information about the study with mothers of Hispanic 
heritage. Face-to-face information classes worked well in our feasibility and pilot studies and we were able to 

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enroll a sufficient number of participants each week. If mothers are interested, the RAs will privately record 
their name and telephone number and schedule them for an enrollment screening telephone call. 
We plan to enroll 10 mother-child dyads per week. However, we have built into the timeline additional time for 
enrollment for each cohort if needed. If we have any difficulty enrolling participants, we will work with both 
health departments and El Centro Hispano to provide advice and assistance. We will also seek the assistance 
of our Community Advisory Board, which will be made up of mothers of Hispanic heritage with a 
3-5-year-old child. 
 
The bilingual project manager will conduct a private telephone screening and ask mothers’ height and weight 
and their child’s gender, birthdate, height, and weight, calculate BMI for mothers and BMI percentile for 
children and ask the questions on The Short Acculturation Scale for Hispanics [52]. If both mother and child 
meet the study criteria, an appointment will be made to meet at the community center to confirm eligibility; the 
bilingual RAs will measure height and weight and confirm BMI and BMI percentile. If eligible, the RA will 
explain, in Spanish, the study, requirements of participants, and the risks and benefits of participating, and 
random assignment; and all questions will be answered. Only the mother and one 3-5 year-old child will be 
eligible to join the study. Childcare will be available for other children the mother brings with her in addition to 
her 3-5-year-old child. Data collection with mother-child dyads will occur in the morning or early afternoon 
when the mother’s older children will be in school. Physiological data collection will be done in a private room. 
Bilingual RAs will collect the following data in the same order: health history questionnaire, sports physical, 
height, weight, waist circumference, triceps and subscapular skinfolds. The mothers will fill out their 
questionnaires in a group with a bilingual RA who will read all questionnaires in Spanish. Data collection will 
take 75 minutes for each mother-child dyad. We have extra time in the schedule for make-up data collection 
At the time of data collection, women will have clinical data collected and will be asked to fill out data forms. A 
sports physical will be conducted on all mothers during the baseline data collection to ensure there are no 
medical problems before engaging in physical activity. The sports physical will be conducted by a bilingual 
nurse practitioner hired for the study with experience in conducting sports physicals and medical clearance in a 
private room. The clinical measurements and data forms should take approximately 75 minutes to complete. 
Women will be encouraged to self-identify any concerns to the study staff. There will be adequate time for 
women to ask questions, and they will be given phone numbers to reach the PI and project manager if they 
have any further questions or concerns 
 
Confidentiality will be protected through a coding mechanism. The names of all participants will be removed 
from the data and a code number assigned. Each participant’s identifying data will be separated from the study 
data, and the key identifying code numbers and the participant’s identification will be kept by the PIs in a 
locked file cabinet in a locked office that only the PI and the project manager will have access to. Data will be 
reported in aggregate form without identifying information by site or individual. All research study personnel will 
be trained in IRB and HIPAA guidelines to maintain the security and confidentiality of the data. Mothers will be 
made aware of the precautions that the research team will take in keeping their data confidential. All identifying 
information will be destroyed at the earliest possible time following completion of the study. Publications arising 
from the study will not contain personal information. All data will be analyzed by groups, with no potential for 
individual participants to be identified. 
 
 
 
 
 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Potential Benefits of the Proposed Research to Human Subjects and Others 

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The major potential benefit of this study is the provision of new knowledge about ways to improve outcomes for 
women of Hispanic heritage with limited English proficiency and their 4-year old children. The intervention 
women will receive valuable information about nutrition and physical activity education, coping skills training, 
and physical activity. Their 4-year old children will receive valuable nutrition information and have an 
opportunity for physical activity. The equal attention control group will receive English as Second 
Language classes and the equal attention control group children will receive free play while their mothers are 
in class. Collection of data on mother’s weight, adiposity, health behavior, and self-efficacy and children’s 
weight and adiposity outcomes should provide information for women to share with their health care providers 
regarding efforts they are making to improve health behaviors in themselves and with their children. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
See 2.3.1 above for assessment of potential risks and benefits 
3 
OBJECTIVES AND ENDPOINTS  
  
Aim 1: Test the efficacy of the intervention in slowing adiposity and weight gain trajectory and improving health 
behaviors (nutrition and physical activity) in 3-5-year-old Hispanic children from Time 1 (0 months [baseline]) to 
Time 2 (9 months [completion of the intervention]) and Time 1 to Time 3 (15 months [after 6 months with no 
contact from the study staff]). 
Aim 2: Test the efficacy of the intervention in decreasing adiposity and weight and improving health behaviors 
and self-efficacy in overweight or obese Hispanic mothers from Time 1 to Time 2 and from Time 1 to Time 3.  
Primary outcomes include slowing of child adiposity (waist circumference and triceps and subscapular 
skinfolds) and weight gain (BMI percentile) trajectory and a decrease in mother’s adiposity and weight (BMI). 
We hypothesize that intervention group children will slow the trajectory of adiposity and weight gain and 
intervention group mothers will decrease adiposity and weight significantly more than the control group. 
Secondary outcomes include child and mothers health behaviors (nutrition and physical activity) and mother’s 
self-efficacy (nutrition and physical activity). We hypothesize that intervention group children and mothers will 
improve health behaviors and mothers will improve self-efficacy significantly more than the control group. 
Aim 3: Identify the mediators through which the intervention influences the trajectory of adiposity and weight 
gain in children and decrease in adiposity and weight in mothers. We hypothesize that health behaviors and 
self-efficacy may mediate adiposity and weight loss in mothers and nutrition and physical activity behaviors in 
children may mediate a slower adiposity and weight gain trajectory.  
Aim 4: Calculate the cost of implementing the intervention for public health departments and the costs for 
mothers participating, from Time 1 to Time 2 and compare these costs to the outcomes of the intervention 
(cost-effectiveness) and the potential economic benefits of these outcomes (cost-benefit analysis). We 
hypothesize that the intervention is primarily focused on knowledge and behaviors in an at-risk population and 
may be cost-effective in comparison with other approaches to managing overweight and obesity. 

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Exploratory Aim: Determine whether intervention group mothers in the overweight versus obese BMI 
category benefit equally from the intervention in adiposity, weight, health behaviors, and self-efficacy.     
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
This study will use a two-group, randomized repeated measures study design to evaluate the efficacy of the 
intervention with 294 dyads of overweight or obese Hispanic mothers and their 3-5-year-old children. The 
mothers in the Healthy Mothers-Healthy Children Intervention group will receive a 12 week intensive 
intervention and 6 months of continued support. The intensive intervention will include 60 minutes of nutrition 
and exercise education and coping skills training and a 45 minute physical activity class and a home-based 
physical activity program handout each week for 12 weeks. The continued support classes for the mothers in 
the intervention group will include 60 minutes of classroom discussion regarding problems they are having with 
nutrition and physical activity for themselves and their children and a 45 minute physical activity class monthly 
for 6 months. The children in the intervention group will receive an intensive intervention (105 minutes total), 
which will include 60 minutes of Color Me Healthy classes [26] and 45 minutes of free play weekly for 12 
weeks. The continued support classes for the intervention children will include a review of the Color Me 
Healthy classes [26] and 45 minutes of free play monthly for 6 months. Each weekly or monthly class for 
mothers and children is a total of 105 minutes. The equal attention control group mothers will receive English 
as a Second Language (ESL) classes for 105 minutes for 12 weekly classes and then monthly classes for 6 
more months. The equal attention control group mothers will receive homework assignments to help them 
practice their English language skills. The homework handouts will be at the same frequency as the Healthy 
Mothers-Healthy Children Intervention group mothers. The equal attention control group children will receive 
105 minutes of free play for 12 weekly classes and then 6 monthly free play classes.  
Data will be collected at Time 1 (0 months [baseline]), Time 2 (9 months [completion of the intervention]) and 
Time 3 (15 months [after 6 months with no contact from the study staff]). Time 2 data will determine the 
magnitude of the intervention effects after the intensive intervention and continued support; Time 3 data 
collection will test efficacy after the mother-child dyads have had sufficient time to implement their new 
nutrition, physical activity, and coping skills on their own. These times were chosen because 3 to 6 months 
after completion of an intervention represents a standard length of time for follow-up in weight reduction 
studies, and gives mothers and children the time necessary to make changes in health behaviors [19]. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The study design will use a two-group randomized repeated measures study design to evaluate the efficacy of 
the intervention with 294 dyads of overweight or obese Hispanic mothers and their 3-5 year old children.  
4.3 
JUSTIFICATION FOR INTERVENTION 
The intervention was pilot tested face-to-face in this population and was found to be feasible and acceptable.  
4.4 
END-OF-STUDY DEFINITION 
 

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A participant is considered to have completed the study if she and her child has completed Time 1 (baseline), 
Time 2 (9 months) and Time 3 (15 months) data collection.  
5 
STUDY POPULATION 
 
Settings. The study will build upon established partnerships between The University of North Carolina at 
Chapel Hill, the Chatham County Health Department and Durham County Health Department. Bilingual 
research assistants (RAs) will distribute brochures, give mothers information about the study, answer 
questions and enroll mother-child dyads. This approach worked well in previous studies [32, 33]. In 2015, the 
Chatham County Health Department provided 82,314 medical visits and 42% (34,572) were provided to 
Hispanic adults and children and the Durham County Health Department provided 78,123 visits and 46% 
(35,936) were provided to Hispanic adults and children. In 2015, the Durham County Health Department had 
650 Hispanic mother and 4-year old child dyads and the Chatham County Health Department had 800 
Hispanic mother and 4-year old child dyads (Total = 1,450; Mean = 725). A total of 78% of Hispanic mothers 
are overweight or obese [34]. Thus it is anticipated that approximately 78% of the mothers at both sites will 
meet inclusion criteria (n = 1,131), and 50% (n = 565) will agree to participate with their 4-year-old child. Of 
those who agree to participate (n = 565), approximately 70% (n = 396) will score a 1.00-2.99 on the Short 
Acculturation Questionnaire for Hispanics establishing low acculturation [35]. These numbers are adequate to 
meet our projected enrollment of 294 dyads. Specifically, we will enroll 36-38 dyads for each cohort in each 
site in each of eight rolling enrollment periods. We will rent space for the intervention from community centers 
in Chatham and Durham Counties as we have done in previous studies (see Letters of Support). The public 
health departments and community centers are situated in the communities where participants live and they 
are either within walking distance from their homes or on bus lines, increasing the probability of successful 
recruitment and retention for the proposed study. In previous studies, the mothers drove to the community 
centers together [23]. The centers have classrooms and playgrounds.  
 
Sample. Inclusion criteria for mothers will be age 18 years or older; self-identification as Hispanic; limited English 
proficiency; little acculturation, as measured by the Short Acculturation Scale for Hispanics [35] with a score from 
1.00 to 2.99; ability to understand spoken Spanish; a BMI >25kg/m2; residence with the child; consent to join the 
study and consent for their child to join the study. Inclusion criteria for children will be age 3-5-years; ability to 
understand spoken Spanish; and a BMI > 25th percentile for age and gender. Health care providers will not be 
asked to give permission for mother-child dyads to join the study. Mothers will fill out a health history 
questionnaire to ascertain if they have a heart murmur, congenital heart disease, family history of sudden death, 
difficulty exercising or psychological problems that would prevent participation. A sports physical will be 
conducted by a bilingual nurse practitioner on all mothers during baseline data collection to ensure that they 
have no medical problems. If a mother answers yes to any of these health history questions or the nurse 
practitioner finds a heart murmur or any other concerns, she will be excluded from the study and referred to a 
health care provider. Dyads will be enrolled in eight cohorts over four years. Each cohort will be enrolled over a 
1-month period. 
5.1 
INCLUSION CRITERIA 
 
Inclusion criteria for mothers will be age 18 years or older; self-identification as Hispanic; limited English 
proficiency; little acculturation, as measured by the Short Acculturation Scale for Hispanics [35] with a score 
from 1.00 to 2.99; ability to understand spoken Spanish; a BMI >25kg/m2; residence with the child; consent to 
join the study and consent for their child to join the study. Inclusion criteria for children will be age 3-5-years; 
ability to understand spoken Spanish; and a BMI > 25th percentile for age and gender. 
5.2 
EXCLUSION CRITERIA 

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Health care providers will not be asked to give permission for mother-child dyads to join the study. Mothers will 
fill out a health history questionnaire to ascertain if they have a heart murmur, congenital heart disease, family 
history of sudden death, difficulty exercising or psychological problems that would prevent participation. A sports 
physical will be conducted by a bilingual nurse practitioner on all mothers during baseline data collection to 
ensure that they have no medical problems. If a mother answers yes to any of these health history questions or 
the nurse practitioner finds a heart murmur or any other concerns, she will be excluded from the study and 
referred to a health care provider. 
5.3 
LIFESTYLE CONSIDERATIONS 
N/A 
5.4 
SCREEN FAILURES 
 
Screen failures will not be consented or enrolled in the study. We will keep track of screen failures and reasons 
why they failed to meet inclusion criteria.  
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Procedures for Minority Recruitment and Enrollment and Challenges 
 
We will hire only bilingual staff, and all recruitment and intervention materials and instruments will be in 
Spanish. Two months before enrollment, the bilingual project manager will give a presentation to staff at both 
public health departments and place Spanish language posters and brochures in each waiting room. The 
posters and brochures will describe the benefits of good nutrition and physical activity and state the eligibility 
criteria for study participation. We will also put ads in local Spanish language newspapers and announcements 
on the local Spanish language radio station with our toll free number. Bilingual RAs will be available in the 
waiting rooms on clinic days to share information about the study with Hispanic mothers. Face-to-face 
information classes worked well in our feasibility and pilot studies and we were able to enroll a sufficient 
number of participants each week [23]. If mothers are interested, the RAs will privately record their name and 
telephone number and schedule them for an enrollment screening telephone call. This technique also worked 
well in our pilot study, which included mother-child dyads with limited English proficiency [23]. Of 82 mother-
child dyads approached in the pilot, 68% (n = 56) consented to participate over 1 month [23].  We plan to enroll 
approximately 10 mother-child dyads per week. However, we have built into the timeline additional time for 
enrollment for each cohort if needed. If we have any difficulty enrolling participants, we will work with both 
health departments to seek advice on how to improve enrollment in the study.  
 
The bilingual project manager will conduct a private telephone screening and ask mothers’ height and weight 
and their child’s gender, birthdate, height, and weight, calculate BMI for mothers and BMI percentile for 
children and ask the questions on The Short Acculturation Scale for Hispanics [35]. If both mother and child 
meet the study criteria, an appointment will be made to meet at the community center to confirm eligibility; the 
bilingual RAs will measure height and weight and confirm BMI and BMI percentile. If eligible, the RA will 
explain, in Spanish, the study, requirements of participants, and the risks and benefits of participating, and 
random assignment; and all questions will be answered. Only the mother and one 3-5-year-old child will be 
eligible to join the study. Childcare will be available for other children the mother brings with her in addition to 
her 3-5-year-old child. Data collection with mother-child dyads will occur in the morning or early afternoon 
when the mother’s older children will be in school. Physiological data collection will be done in a private room. 
Bilingual RAs will collect the following data in the same order: health history questionnaire, sports physical, 
height, weight, waist circumference, triceps and subscapular skinfolds. The mothers will fill out their 

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questionnaires in a group with a bilingual RA who will read all questionnaires in Spanish. Data collection will 
take 75 minutes for each mother-child dyad. We have extra time in the schedule for make-up data collection. 
 
Procedures for Minority Retention and Challenges 
 
Weight management studies typically have attrition rates ranging from 10%-30% [19]. To strengthen retention, 
our classes will be interactive, with culturally and linguistically tailored content developed to engage and 
sustain the interest of the mother-child dyads. Mothers who miss class will be offered a make-up class over the 
phone, and reminded when the next class will be held. Additional incentives will include childcare for other 
children who accompany mothers and their 3-5-year-olds to class and recipes and handouts in Spanish on 
how to improve their children’s nutrition and physical activity behaviors. Mothers will be asked for telephone 
numbers of several family members and permission to call them if we cannot reach them. We will be as flexible 
as possible in scheduling enrollment and data collection appointments and provide tokens of appreciation such 
as birthday cards and a quarterly newsletter with updates on the study. Mothers in both groups will receive $25 
after each data collection. These approaches proved successful in our pilot study with Hispanic mothers with 
limited English proficiency, where attrition was only 9%-15% [23] and those mothers who stopped coming had 
moved out of the state. We will make every effort to keep our attrition rate lower than the projected 15%. If 
retention rates drop below 85%, we will contact the mothers to ask why they stopped coming and develop 
strategies to meet the needs of each mother to assist them to continue in the study if possible.  
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION.   
 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
Intensive Intervention for Mothers 
The intensive intervention classes are based on the classes from our Family Partners for Health study, 
adapted for Hispanic mothers with limited English proficiency and their 3-5-year-old children [23, 36, 37]. 
Classes will be run by a bilingual interventionist and will be 60 minutes long with 18-19 mothers. We chose 18-
19 mothers since the enrollment is rolling and these mothers will be enrolled together and this cohort approach 
worked well in our previous studies [23, 37]. Classes will include nutrition and physical activity education and 
coping skills training using problem solving, assertiveness training, cognitive restructuring, and conflict 
resolution around problems of nutrition and physical activity for mothers and their children. The nutrition 
classes will include content on understanding calories, protein, carbohydrates and fat, making healthy 
substitutes that are culturally acceptable, choosing healthy foods when eating out at a favorite fast food 
restaurant, using actual menus, and understanding how portion control can make a difference for them and 
their children using food models and food labels in Spanish. Mothers will receive information on how to shop as 
economically as possible and how to shop at local farmers’ markets, which are geographically close to the 
mother’s homes, where they may have better access to fresh fruits and vegetables. At the end of each class, 
mothers will be asked to set a nutrition or physical activity goal for the coming week for themselves and their 4-
year-old child.  
 
Physical activity classes will be held for 45 minutes after the intensive intervention classes and will include a 
warm-up and then activities such as Zumba, Kick Boxing, walking, use of light weights and stretch bands, and 
a cool-down. The bilingual interventionist will reinforce the importance of physical activity and ways to increase 
physical activity for mothers and their children. The importance of decreasing sedentary behaviors for mothers 
and children will be reinforced in all classes. During the first week, each mother will receive a pedometer and 
log book for self-feedback. Mothers will be encouraged to bring their pedometer log book in weekly for the 

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bilingual interventionist to review. Pedometers will be used as a part of the intervention instead of a Fitbit 
because some of the women may not have a computer in their home to upload their data. Mothers will be 
encouraged to increase their physical activity weekly by small increments until they are physically active 30 to 
60 minutes a day on most days of the week with their 3-5-year old child. Missed physical activity classes will 
not be made up. Mothers in the intervention group will be encouraged to develop their own home-based 
physical activity program using suggestions given in the physical activity class and a home-based physical 
activity handout in Spanish given after each physical activity class ti increase their and their child’s physical 
activity. The handouts will be reviewed with the mothers and physical activities demonstrated by the bilingual 
interventionist.  
 
Intensive Intervention for Children 
 
The children’s classes will include a 60 minute session plus 45 minutes of supervised free play with 18-19 
children at the same time their mothers are in class. Each class will have 1 teacher and 3 teacher assistants to 
ensure safety. The Color Me Healthy [26] curriculum, which consists of 12 classes in Spanish, was purchased 
and used for the pilot study [23]. All of the classes are at a 3-5-year-old developmental level and include a CD 
with music and a song about the class of the week, colorful picture cards, and opportunities for the children to 
try new fruits and vegetables. Each week the bilingual interventionist will give mothers a Color Me Healthy [26] 
handout in Spanish that includes strategies for feeding their children healthier meals and snacks and 
increasing their daily physical activity. While their mothers are in physical activity class, the children will have 
45 minutes of physical activity (supervised free play) in a playground at the community center or dance and 
actively play with the bilingual interventionist if it is raining.  
 
Continued Support for Mothers and Children 
 
During continued support, intervention mother-child dyads will return to the community center for classes once 
a month for 6 months. The mothers will receive a calendar at the completion of the intensive intervention 
classes with the dates and times and a reminder phone call several days before each class. As a part of the 
intervention, mothers will be weighed and then have the opportunity to engage in a discussion run by the 
bilingual interventionist, who will help mothers solve problems they have encountered related to nutrition and 
physical activity for themselves and their children for 60 minutes and then receive a 45 minute physical activity 
class. The children will meet with a bilingual interventionist to review a class from the Color Me Healthy [26] 
curriculum for 60 minutes and then receive 45 minutes of free play. If a mother and child miss a class, the 
bilingual interventionist will call and ask how the mother and child are doing and give the date of the next class. 
Continued support classes will not be made up.  
 
Equal Attention Control Group 
 
Mothers in the control group will receive English as a Second Language (ESL) classes taught by professional 
ESL teachers; they will receive the same number of contacts and time as the intervention group mothers (105 
minutes weekly for 12 weeks and 105 minutes monthly for 6 months). The ESL classes will be offered because 
when exit interviews were conducted after the pilot study [23], mothers were asked if they “were not in the 
intervention group, what type of classes would they want?” The mothers (90%) wanted ESL classes to improve 
their English. Providing these classes to the control group most likely will improve enrollment and retention. 
Children in the control group will have free play while their mothers are in class and will receive the same number 
of contacts and times as the children in the intervention group (105 minutes weekly for 12 weeks and 105 minutes 
monthly for 6 months). The control classes will be held on separate days of the week from the intervention 
classes in the same community centers. Data will be collected from the mother-child dyads in the control group 
at Time 1, Time 2, and Time 3; and the mothers will receive $50 each time. Mothers will be called several days 
before classes and data collection to remind them. Mothers will receive a pedometer and log book after they 

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have completed Time 3 data. Attrition rates in our previous studies were equal in the intervention and control 
groups and ranged from 9% to 15% [23]. 
6.1.2 ADMINISTRATION AND/OR DOSING 
 
See 6.1.1 for details 
 
6.2 
FIDELITY 
 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
Fidelity of the Intervention 
 
We have structured the fidelity of the intervention using the NIH five category Treatment Fidelity Framework 
[38]. For category one, treatment design, both the intervention and control condition will receive different 
content but will be the same length, number, and duration of contact over time. The bilingual interventionists 
will have experience teaching health interventions, and the theoretical model is clearly articulated. For category 
two, training, the bilingual interventionists will be trained by the PI and teach back the intervention to the PI. 
For category three, delivery of the intervention, integrity will be assessed by observation of two randomly 
selected classes per month by the project manager who will use a checklist to score classes based on pre-
identified content, and drift will be defined as teaching less than 80% of protocol content. If drift occurs, the 
bilingual interventionists will be retrained until the protocol is followed consistently. We will also use a list of 
behavioral indicators to assess the interventionists’ skills in facilitating classes, engaging mother-child dyads, 
role playing, problem solving, providing positive feedback, and goal setting. Retraining will be provided if 
problems are found. In our pilot study [23], we had little difficulty in maintaining consistency of the intervention. 
The bilingual interventionists will collect data on attendance at each class, reasons for non-attendance, and 
make-up classes provided. Category four, receipt of treatment, will be evaluated during the class by the 
bilingual interventionist who will assess understanding and answer all questions. Category five, enactment of 
intervention skills, will be evaluated during the six monthly continued support classes by the bilingual 
interventionist. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
After enrollment and baseline assessment, dyads will be randomized to either the intervention or control group 
using a computer-generated randomization table, stratifying by BMI group, overweight (25 – 29.9 kg/m2) and 
obese (>30 kg/m2), and utilizing blocking to help ensure balance between the groups. Mothers will be informed 
of their group assignment by telephone. We have not included fathers, as in previous studies in this population, 
because the majority of fathers work 6 days a week and cannot attend class [7, 23]. Data collection research 
assistants will be blinded to group status.  
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
See 6.2.1 for details 
6.5 
CONCOMITANT THERAPY 
 

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N/A 
 
6.5.1 RESCUE THERAPY 
 
N/A 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
The intervention will only be discontinued after consultation with the study team and the program officer.  
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. 
 
An investigator may discontinue a participant from the study for lost-to-follow up and unable to contact subject. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded. Subjects who sign the 
informed consent form and are randomized but do not receive the study intervention may be replaced.  
Subjects who sign the informed consent form, and are randomized and receive the study intervention, and 
subsequently withdraw, or are discontinued from the study will not be replaced. 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if she fails to return for scheduled visits and study staff are 
unable to contact the participant after at least 3 attempts.  
 
The following actions must be taken if a participant fails to return for a required study visit: 
 
The site will attempt to contact the participant, reschedule the missed visit, counsel the participant on the 
importance of maintaining the assigned visit schedule and ascertain if the participant wishes to and/or should 
continue in the study. 
 
Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to regain 
contact with the participant (where possible, 3 telephone calls. These contact attempts will be documented in 
the participant’s medical record or study file.  
 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from the 
study with a primary reason of lost to follow-up. 
 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 

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8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
Variables and Their Measurement 
Respondent 
Time 1 
Time 2 
Time 3 
Short Acculturation Questionnaire for Hispanics 
Mother 
X 
 
 
Health History Questionnaire 
Mother 
X 
 
 
Sports Physical  
Mother  
X 
 
 
Adiposity (Primary Outcomes) 
 
 
 
 
   Waist Circumference 
Mother/Child 
X 
X 
X 
   Triceps and Subscapular Skinfolds 
Mother/Child 
X 
X 
X 
Weight Status (Primary Outcomes) 
 
 
 
 
   Height/Weight 
Mother/Child 
X 
X 
X 
   BMI/BMI Percentile 
Mother/Child 
X 
X 
X 
Health Behavior  
 
 
 
 
   Adult Health Behavior Survey 
Mother 
X 
X 
X 
   Health Promoting Lifestyle Profile II 
Mother 
X 
X 
X 
   24-hour Food Recall for 3 days 
Mother for Self/Child 
X 
X 
X 
   Accelerometer for 7 days 
Mother for Self/Child 
X 
X 
X 
Self-Efficacy  
 
 
 
 
   Eating Self-Efficacy Scale 
Mother 
X 
X 
X 
   Exercise Self-Efficacy Scale 
Mother 
X 
X 
X 
Demographic Data 
Mother for Self/Child 
X 
 
 
Health History Update Questionnaire 
Mother for Self/ Child 
 
X 
X 
Process Evaluation Bi-Monthly 
Project Manager 
 
 
 
Exit Interviews 
Mother 
 
 
X 
Time 1 (0 months [baseline]); Time 2 (9 months [completion of the intervention]); Time 3 (15 months [after 6 months with no contact from the study 
staff]). 
 
8.2 
SAFETY ASSESSMENTS 
 
N/A 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS 
See Data Safety Monitoring (DSMP) Below 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
See DSMP Below 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
See DSMP Below 
 
8.3.3.1 SEVERITY OF EVENT 
See DSMP Below 
 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
 
 
 

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Data and Safety Monitoring Plan 
 
Study Identification 
 
NIH Study Number – 1R01NR017199-01 
 
Study Title – Healthy Mothers: Healthy Children: An Intervention with Hispanic Mothers and their Young 
Children 
 
Principal Investigator – Hudson Santos, PhD, RN 
Study Overview 
The overall goal of this project is to determine whether a nutrition and physical activity education, coping skills 
training, exercise program, and a home-based exercise program will decrease adiposity and weight, and 
improve health behaviors and self-efficacy in mothers of Hispanic heritage and slow excessive adiposity and 
weight gain in their 4-year old children. The DSMP outlined below for the proposed study will adhere to the 
protocol approved by The University of North Carolina at Chapel Hill (UNC-CH) Institutional Review Board (IRB) 
and the National Institutes of Health (NIH) and the National Institute of Nursing Research (NINR).  
  
SECTION A. Monitoring Entity 
 
Considering the study rationale, population, procedures, and the risk: benefit profile as outlined, the overall risk 
level for participation in this study is classified as no more than minimum risk. 
 
1)  
Individual Roles and Responsibilities 
 
An Executive Committee will be formed to oversee the conduct of the study. The committee will be comprised of 
nine members: Dr. Santos (Principal Investigator [PI]) and the Study Investigators, Drs. Ammerman, Crandell, 
Evenson, Faith, Peragallo-Montano, Perreira, Perrin, and Waters. The PI will Chair the Committee, which will 
meet monthly to review the activities of the study including management, personnel, recruitment, performance, 
and any emerging problems.  
 
The Independent Monitor (ISM) for this study will be Dr. Mary Lynn. Dr. Lynn has been the Inaugural Assistant 
Director for Operations of the Office of Human Research Ethics at UNC-CH, which was preceded by six years 
as the IRB Chair and Chair of the School of Nursing (SON) IRB. Dr. Lynn is not associated with this research 
project and thus works independently of the PI. Dr. Lynn is not one of the key personnel involved in this grant. 
She is qualified to review the participant safety data generated by this study because of her unique expertise in 
human research ethics and serving as the ISM on multiple previous studies.  
 
B. Procedures for Safety, Risk, and Confidentiality 
 
1) 
Monitoring Study Safety  
 
From the initial screening of participants by inclusion and exclusion criteria to the informed consent process to 
the provision of participant study instruction to staff training in Good Clinical Practices (GCP) and regulations 
pertaining to the Conduct of Human Participant Research to weekly contact with participants to internal 
monthly quality control audits and protocol fidelity monitoring to the real-time review of adverse events (AE) 
and serious adverse events (SAEs) by the PI, Study Investigators and the ISM, the study will be carefully 
oversighted.   
 

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Drs. Santos, Ammerman, Crandell (Study Statistician), Evenson, Faith, Lynn (ISM) Peragallo-Montano, Perreira, 
Perrin, and Waters will review the data for this study quarterly. We will examine participant accrual and  
adherence to the protocol regarding demographics and inclusion and exclusion criteria, and compliance of 
treatment, AE and SAE rates quarterly, and report regarding statistical power implications of dropouts and 
missing data annually. 
 
Data on compliance to the intervention will be collected weekly by the Project Manager (PM) and reviewed 
quarterly by the Study Investigators, Study Statistician, and the ISM. Compliance on the part of participants will 
be evaluated by attendance and process evaluation as outlined in the study. If intervention attendance drops 
below 85%, the mothers who have stopped coming will be called to ask for feedback. Using information gained 
from these phone interviews, the PI will schedule a meeting with the Study Investigators and the ISM to discuss 
methods for improving compliance. 
 
As in previous studies, the PI and the Study Statistician will oversight and train the PM to establish a system to 
ensure the verification of source data compliance. The source data will include original records necessary for 
the reconstruction and evaluation of the clinical trial. It will be clear who documented the data, documentation 
will be readable, signatures identifiable, contemporaneous, original copy, accurate and consistent, long-lasting 
and durable, available and accessible, complete, consistent, credible, and corroborated. All data will be first 
checked by two separate Research Assistants (RAs) at different times. REDCap will be used as our Research 
Electronic Data Capture System. The PI has been trained in REDCap and has used it in previous studies and 
REDCap is supported by UNC-CH. The REDCap database creation will be oversighted by Dr. Crandell (Study 
Statistician). Dr. Crandell will run comparisons and trained RAs will compare against source data and make 
corrections as needed. A data log book will be created to establish an audit trail for compliance as the PI has 
done in previous studies.  
 
Drs. Santos, Ammerman, Crandell, Evenson, Faith, Peragallo-Montano, Perreira Perrin, and Waters will 
personally conduct and supervise the study. We will register the study in ClinicalTrials.gov. We will follow the 
protocol and ensure all study staff follow the protocol. All staff assisting with the study will be informed of their 
obligations. We will ensure informed consent, approval and reporting. We will report to the NIH/NINR Program 
Officer, Dr. Mary Roary, any AEs or SAEs. We will maintain adequate records and make them available for 
inspection. We will ensure initial and continuing review by UNC-CH IRB and will report all changes to research 
and involving risks to subjects, and not make any changes without IRB approval except where necessary to 
eliminate immediate hazards. All of the study team are CITI trained and follow the Good Clinical Practice (GCP) 
Guidelines.  
 
2)   
Minimizing Research-Associated Risk 
 
Diligent study safety monitoring will be conducted by the PI as follows. The PI will work with the IRB to set up a 
schedule of selected cases to ensure compliance with IRB requirements. The PI and Study Investigators have 
worked closely with the IRB in previous studies providing the data requested for audits as required. Risks to 
human subjects will be minimized through the utilization of establish protocols that have worked well in 
previous studies. We are aware that AEs and SAEs may occur and an Adverse Event Monitoring Committee 
will monitor their occurrence and the overall risk of the study to both mothers and their children.  
 
Mothers who express fatigue during sessions will be excused from the session and another time convenient for 
them will be scheduled to make up the content. If a mother expresses fatigue during data collection, the data 
collection session will be terminated immediately, and a follow-up appointment scheduled. No mothers 
expressed fatigue in the PI’s previous studies. It is not anticipated that the classes or data collection will cause 
any adverse effects, but participants will be encouraged to identify any concerns to the study staff. All mothers 
and their children will continue to receive routine medical care from their health care providers throughout the 
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known social or legal risks for the mothers who consent to participate for themselves and consent for their 
children in this study. There will be adequate time for mothers to ask questions, and they will be given phone 
numbers to reach the PI and PM if they have any further questions or concerns.  
 
Institution-Wide Assurances will be assured by the use of the protocol, which will be conducted fully in 
keeping with the signed PI in accordance with UNC-CH IRB, NIH, and NINR.  
  
3)  Protecting Confidentiality of Participant data Participant Screening and Enrollment 
 
All data from participants screened for the study will be entered into the REDCap electronic study database. 
Designated research staff will collect, gather, and enter required data (written informed consent, Health 
Insurance Portability and Accountability Act (HIPAA) authorization, medical history and demographics) onto 
study data forms. Screened patients who do not meet study eligibility will have specific screening data entered 
into the study database. The collected data will be helpful in examining the patient population and feasibility of 
enrollment criteria and will include gender, age, race and reason for exclusion. All dates will be shifted and 
other Personal Health Information (PHI) will be removed from the study database upon study completion. All 
data obtained from this study will be used for research purposes only and will comply with Federal HIPAA 
regulations.  
 
Written informed consent will be obtained from each participant at entry into the study. Informed consent is 
obtained by the following process. The participant will be read the study consent form in Spanish. The bilingual 
PM or trained bilingual RA will meet with the participant to review the form, to confirm the participant’s 
understanding of the study, and to answer any questions that the participant might have. Once the participant 
demonstrates understanding of the study and agrees to participate in the study, the consent will be signed in the 
presence of the bilingual PM or bilingual RA. The IRB will oversight yearly renewal of consent forms and the PI 
and the research team will provide data as requested for the renewal.  
 
Confidentiality will be protected through coding mechanisms. The names of all participants will be removed from 
the data and a code number assigned. Each participant’s identifying data will be separated from the study data, 
and the key identifying code numbers and the participant’s identification will be kept by the PI in a password 
protected computer in a locked office that only the PI and the PM will have access to. Data will be reported in 
aggregate form without identifying information by site or individual. All research study personnel will be trained 
in IRB and HIPAA guidelines to maintain the security and confidentiality of the data. Mothers will be made aware 
of the precautions that the research team will take in keeping their data confidential. All identifying information 
will be destroyed at the earliest possible time following completion of the study. Publications arising from the 
study will not contain personal information. All data will be analyzed by groups, with no potential for individual 
participants to be identified. 
 
Case Report Forms. All proposed study specific case report forms (source documents) for data collection will 
be designed by the PI and PM in concert with the Study Statistician and transferred by the PM into electronic 
Case Report Forms (eCRFs) for use in the study’s REDCap database. These study specific eCRFs source 
documents (study logs for correspondence, contacts, compensation and other forms such as pre-eligibility 
screens) will be coded by the participant’s unique study identification number for all data collected including 
study instruments will be maintained in the participant research record that will be made accessible to study 
monitors. Completed instruments that require a signature on a paper CRF will be scanned and uploaded into 
the study database as well as maintained on file in accordance with UNC-CH policies and applicable Federal 
Regulations for the Conduct of Human Participant Research. 
  
Binders. The PM will prepare and maintain a participant-specific binder for each participant containing all non-
eCRFs records. A regulatory file will also be maintained to include the IRB approved Protocol, original 

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Informed Consent documents, HIPAA forms and other study-related regulatory documents. All paper research 
records and CRFs will be maintained in a locked file cabinet in a secure facility within the SON. Access to the 
research records, study database and PHI will be restricted to study personnel as approved by the PI and IRB. 
As with all studies conducted at the UNC-CH, this study is also eligible for a random audit by Office of 
Compliance.  
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data capture and 
management. 
  
Data Security. Ensuring data security, compliance with 21 CFR 11 and maintaining the integrity of PHI is a top 
priority. 
  
Data Entry. Each participant will be assigned a unique study identifier, all PHIs will be masked, and data 
exports will be limited to the PI, the PM, and Study Statistician for generating reports and the conduct of 
statistical data analysis. 
  
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, storage and 
processing. The PM will conduct monthly monitoring of the study database and generate a report for the PI to 
review at team meetings. Standing agenda items for these meetings will include participant recruitment and 
retention, AEs, SAEs, protocol deviations, data integrity and overall study conduct. 
  
Database Protection. The REDCap database will be secured with password protection. The informatics 
manager receives only coded information, which is entered into the database under those identification 
numbers. Electronic communication with outside collaborators involves only unidentifiable information. 
 
SECTION C. Procedures for Identifying, Reviewing and Reporting Adverse Events 
 
1)  Identifying. Potential risks identified for participants are outlined in the Protection of Human Participants 
and will also be outlined in the IRB approved informed consent document. 
 
Dr. Mary Lynn (Chairperson of UNC-CH School of Nursing Human Participant Research Review Committee 
and ISM) will chair the Adverse Event Monitoring Committee, which will include Drs. Santos (PI), Ammerman, 
Crandell (Study Statistician), Evenson, Faith, Peragallo-Montano, Perreira, Perrin, and Waters and the PM. The 
committee will meet every 3 months or more often as warranted, to review data related to AEs and SAEs and 
assure that safety standards are maintained. Despite usual precautions, we are aware that AEs and SAEs may 
occur, and this committee will monitor their occurrence and the overall risk of the study to both mothers and 
their children. We will develop a system to test whether abnormalities are equally distributed between the 
intervention and equal attention control groups. Data will be presented to the committee if a significant increase 
in abnormalities is noted. The committee will be asked to establish measurable standards that must be met 
before they recommend modification of the study on the basis of safety. These standards will be clearly 
delineated in the meeting minutes and approved by the committee. The committee will provide the PI with 
recommendations regarding problems that would require modification for safety reasons. Minutes of each 
meeting will be kept, and all actions and decisions documented to establish an audit trail. Dr. Crandell, the 
Study Statistician, will be instructed by the PI to prepare the randomization plan for the study and prepare 
reports for the committee under the direction of Dr. Lynn (Chair and ISM). 
 
2)  Reviewing. Adverse events will be assessed and graded as follows.  
 
Expected/Anticipated—Identified in nature, severity, or frequency in the current protocol, informed consent, 
investigator brochure, or with other current risk information. 

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Unexpected/Unanticipated—Not identified in nature, severity, or frequency in the current protocol, informed 
consent, investigator brochure, or with other current risk information. 
 
More Prevalent—Occurs more frequently than anticipated or at a higher prevalence than expected. 
 
Serious—Results in death, is life threatening, requires inpatient hospitalization or prolongs existing 
hospitalization, results in persistent or significant disability/incapacity, cancer, overdose, or causes a congenital 
anomaly/birth defect. 
  
The relationship of AE to study participation will be determined by the Adverse Monitoring Committee as 
follows.  
 
Unrelated—There is not a reasonable possibility that the adverse event may have been caused by the drug, 
device or intervention. 
 
Possibly Related—The adverse event may have been caused by the drug, device, or intervention, however 
there is insufficient information to determine the likelihood of this possibility. 
 
Related—There is a reasonable possibility that the adverse event may have been caused by the drug, device 
or intervention. 
  
3)  Reporting. The PI will responsible for ensuring that all AE and SAEs are reported to the NIH/NINR (Dr. 
Roary) and UNC-CH’s IRB in compliance with their requirements.  
 
Any AE will be reported by the PI to the Adverse Event Monitoring Committee within one week. An incident 
report will be created and sent by electronic email by the PI to Drs. Ammerman, Crandell (Study Staistician), 
Evenson, Faith, Lynn (ISM) Peragallo-Montano, Perreira, Perrin, and the PM. The PI will follow-up with the 
mother and child and will prepare a report. The AEs will be reviewed every three months and a report prepared 
for the Human Participants Committee and Dr. Roary at NIH/NINR. Process notes will be kept concerning any 
decisions.  
 
Any SAE or deaths that occur during the study will be reported by telephone immediately to the Human 
Participants Research Review Committee Chairperson and Dr. Lynn (ISM) and to NIH/NINR (Dr. Mary Roary). 
An incident report will be sent by electronic mail by the PI to Drs. Ammerman, Crandell, Evenson, Faith, 
Peragallo-Montano, Perreira, Perrin, and the PM. The PI will follow-up immediately with the mother and child to 
investigate and prepare a report for all members of the Human Participants Committee and comply with all 
regulations regarding the reporting of SAEs. If the PI is unavailable, Dr. Perreira will be on-call in the PI’s 
absence. The PI or Dr. Perreira in the PI’s absence will be responsible for complying with all regulations 
concerning the reporting of a SAE and will prepare a full report for NIH/NINR. It is not expected that the 
committee will be involved in the decision to terminate the intervention for a study participant related to any 
adverse event. The PI will meet with the Study Investigators and the PM and seek input from the Program 
Officer (Dr. Mary Roary) and Dr. Lynn (ISM). Process notes will be kept concerning any decisions. 
 
4)  Examples of Potential Reportable Adverse Events. An AE is reportable is it meets all of the following 
criteria: 1) is unexpected 2) is related and/or possibly related, and 3) is serious and/or suggests that the 
research places subjects or others at a greater risk of physical or psychological harm than was previously 
known or recognized. Additionally, per UNC-CH’s policy all participant deaths, protocol deviations, complaints 
about the research, and breaches of confidentiality are reportable events.  
 

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An example of an AE would be that a 3-5-year old child decreases from the 25th percentile (normal or healthy 
weight) to below the 5th percentile (underweight) at the next data collection. The steps to be taken include 
withdrawing the child and their mother from the study. The PI will immediately contact Dr. Perrin (Pediatrician), 
Dr. Lynn (ISM), the IRB Contact person, and Program Officer Dr. Roary at NIH/NINR. The PI will assist the 
mother to call her Pediatrician and set up an immediate appointment to have her 4-year old child evaluated 
and ensure that follow-up was received.  
 
An example of an SAE would be the death of a participant from acute renal failure, which although would be 
viewed as unexpected and unrelated to the intervention is nonetheless a reportable serious event. No further 
steps would be taken except to review, grade and report the event.  
 
5) Safety Review Plan. Study progress and safety will be reviewed monthly (and more frequently if needed). 
Progress reports, including participant recruitment, retention/attrition, and AEs will be provided to Dr. Lynn (ISM) 
following each of the monthly reviews. An annual report will be compiled and will include a list and summary of 
AEs and SAEs. In addition, the annual report will address (1) whether adverse event rates are consistent with 
pre-study assumptions; (2) reason for dropouts from the study; (3) whether all participants met entry criteria; (4) 
whether continuation of the study is justified on the basis that additional data are needed to accomplish the 
stated aims of the study; and (5) conditions whereby the study might be terminated prematurely. The annual 
report will be signed by Dr. Lynn (ISM) and will be forwarded to the IRB and NIH/NINR. The IRB will review 
progress of this study on an annual basis. 
 
SECTION D. Multi-Site Monitoring and Compliance 
This is not a multi-site study. 
  
SECTION E. Assessment of External Factors  
The PI will conduct a semiannual assessment of external factors through a review of literature related to new 
developments in the areas of wound management, pain, exercise and other approaches that may have an 
impact on the safety of participants or on the ethics of the study. 
  
SECTION F. Interim Analysis 
The PM will generate semi-annual qualitative interim analysis reports on data obtained during phone call and 
returned end-of-study surveys to understand issues related to the uptake, usability, and adoption of this 
platform among this population. We will evaluate the screening and enrollment procedures, barriers to 
participation and retention, acceptability, technology problems encountered if any, and user feedback from the 
participants and providers. This information gained from this structured process will be used to both guide the 
refinement of the current protocol and to inform the design of a larger efficacy trial. There are no planned 
stopping rules for this study. 
 
8.3.3.3 EXPECTEDNESS  
 
N/A 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
See DSMP above for detail 
8.3.5 ADVERSE EVENT REPORTING  

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See DSMP above for detail 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
See DSMP above for detail 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
See DSMP above for detail 
8.3.8 EVENTS OF SPECIAL INTEREST  
 
N/A 
 
8.3.9 REPORTING OF PREGNANCY  
 
If a woman becomes pregnant while she is in the study she will be withdrawn and follow-up ensured with her 
obstetric health care provider.  
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
See DSMP above for detail 
8.4.2  UNANTICIPATED PROBLEMS REPORTING  
See DSMP above for detail 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
N/A 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
Aim 1: Test the efficacy of the intervention in slowing adiposity and weight gain trajectory and improving health 
behaviors (nutrition and physical activity) in 4-year-old Hispanic children from Time 1 (0 months [baseline]) to 
Time 2 (9 months [completion of the intervention]) and Time 1 to Time 3 (15 months [after 6 months with no 
contact from the study staff]). 

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Aim 2: Test the efficacy of the intervention in decreasing adiposity and weight and improving health behaviors 
and self-efficacy in overweight or obese Hispanic mothers from Time 1 to Time 2 and from Time 1 to Time 3.  
Primary outcomes include slowing of child adiposity (waist circumference and triceps and subscapular 
skinfolds) and weight gain (BMI percentile) trajectory and a decrease in mother’s adiposity and weight (BMI). 
We hypothesize that intervention group children will slow the trajectory of adiposity and weight gain and 
intervention group mothers will decrease adiposity and weight significantly more than the control group. 
Secondary outcomes include child and mothers health behaviors (nutrition and physical activity) and mother’s 
self-efficacy (nutrition and physical activity). We hypothesize that intervention group children and mothers will 
improve health behaviors and mothers will improve self-efficacy significantly more than the control group. 
Aim 3: Identify the mediators through which the intervention influences the trajectory of adiposity and weight 
gain in children and decrease in adiposity and weight in mothers. We hypothesize that health behaviors and 
self-efficacy may mediate adiposity and weight loss in mothers and nutrition and physical activity behaviors in 
children may mediate a slower adiposity and weight gain trajectory.  
Aim 4: Calculate the cost of implementing the intervention for public health departments and the costs for 
mothers participating, from Time 1 to Time 2 and compare these costs to the outcomes of the intervention 
(cost-effectiveness) and the potential economic benefits of these outcomes (cost-benefit analysis). We 
hypothesize that the intervention is primarily focused on knowledge and behaviors in an at-risk population and 
may be cost-effective in comparison with other approaches to managing overweight and obesity. 
Exploratory Aim: Determine whether intervention group mothers in the overweight versus obese BMI 
category benefit equally from the intervention in adiposity, weight, health behaviors, and self-efficacy.     
9.2 
SAMPLE SIZE DETERMINATION 
 
A total of 250 mother-child dyads, or 125 dyads in each randomized group, are expected to complete the 
study. However, we will enroll 294 mother-child dyads (n = 588 participants) or 147 dyads per group, to take 
into account a 15% attrition rate. Our previous studies with Hispanic mothers with limited English proficiency 
and their children have had attrition rates ranging from 9% to 15% [23, 33]. Power calculations were performed 
with POWERLIB20 SAS/IML modules, which incorporate methods described in Muller [39]. These methods 
calculate power for a general linear multivariate model that includes repeated measures data structures, of 
which a two-group longitudinal design is a special case. Power was calculated on the use of a separate 
multivariate model for each outcome addressed in the aims, incorporating measurements at all available time 
points. Effect size estimates were based on the pilot data [23], where estimated within-subject correlation and 
standardized mean difference were .25 and .53, respectively, for mothers’ BMI and .30 and .59, respectively, 
for children’s BMI percentiles. For each outcome, power was computed for a test of the time by treatment 
interaction at a two-sided significance level of .05. For an analyzable sample of 125 mother-child dyads per 
group (total of 250 mother-child dyads), calculated statistical power exceeds 95% for both the test of children’s 
BMI percentiles in Aim 1 and the test of mothers’ BMI in Aim 2; if the within subject correlations and 
standardized mean differences are lower than observed in the pilot at .20 and .45, respectively, statistical 
power will nonetheless exceed 80%. A formal power analysis was not conducted for Aim 3 because the focus 
is on estimation (rather than testing) of direct and indirect mediation effects. Nonetheless, based on Shrout and 
Bolger [40], a sample size of 80 to 85 should provide power in the 70% to 85% range to detect medium effects 
of the intervention on the mediator (e.g., maternal self-efficacy), and the mediator on the outcomes (e.g., 

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mother’s BMI) with a two sided .05 significance level. Our 250 dyads should provide an adequate sample to 
quantify mediation of the relevant variables. 
9.3 
POPULATIONS FOR ANALYSES 
 
Means, standard deviations, minimums, medians, and maximums will be determined for each continuous 
variable; frequencies and percentages will be tabulated for each categorical variable. Preliminary analyses will 
be performed to determine whether, despite randomization, the intervention and control groups were unbalanced 
on gender, age, or income. Any variable with an imbalance between the groups at baseline will be examined to 
determine whether it is related to any of the outcome variables. If significant relationships are identified, the 
variable will be included as a covariate in the models for the affected outcome(s) as a potential confounder. An 
intent-to-treat analysis will be used in which all subjects are included in the analysis and analyzed according to 
their initial randomized assignment. 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
9.4.4 SAFETY ANALYSES 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
9.4.6 PLANNED INTERIM ANALYSES  
9.4.7 SUB-GROUP ANALYSES 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
9.4.9 EXPLORATORY ANALYSES 9.5  
9.4.10 DATA ANALYSIS 
 
Aim 1: To test the efficacy of the intervention in decreasing trajectory of adiposity and weight gain in 4-year-old 
children, separate mixed models will be used to test longitudinal differences between the intervention and 
control group means for each outcome across the study period. Mixed effects models, with a random intercept 
to account for between-mother or between-child differences, will be used for repeated measures analyses of 
each outcome (child BMI percentile, waist circumference, and triceps and subscapular skinfolds). The 
dependent variable will be will be the outcome at each of the three time points; the model will include time point 
(categorical), intervention group, and the interaction between the two.  A test of this interaction will serve as the 
overall test of intervention effect, and step-down tests will be conducted to compare Time 2 and Time 3 to Time 
1, and to estimate how or whether the intervention effect changed from Time 2 to Time 3, using a Hochberg 
correction to account for multiple comparisons [41, 42]. Results will be summarized through the least-squares 
means for each group at each time point and the mean difference and corresponding 95% confidence interval.  
 
Aim 2: To test the efficacy of the intervention in decreasing adiposity and weight in mothers, we will fit mixed 
models analogous to those described for Aim 1 with each of the primary outcomes (mother’s BMI and adiposity 
measures: waist circumference, and triceps and subscapular skinfolds) and secondary outcomes (child health 
behaviors: nutrition and physical activity, mother’s health behaviors: nutrition and physical activity, and 
mother’s self-efficacy: nutrition and physical activity). 
 
Aim 3:  To identify the mediators through which the intervention influences weight management in mother-child 
dyads, the approach of Shrout and Bolger [40] will be employed. This method, based on bootstrapping, builds 
on established mediation testing procedures, such as the Baron and Kenny approach [43] and the Sobel test 
[44]. Mediation analyses test pathways by which an explanatory variable (X) is theorized to influence the 

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mediator (M), which in turn influences the outcome (Y). Models will be conceptualized for each measure of 
weight and adiposity for mothers identified in Aim 1 (Y) and for each proposed mediator (M), relative to the 
randomized intervention group (X). For each model, an effect ratio (defined as the ratio of the indirect effect to 
the total effect, yielding the proportion of the effect that is mediated) and its bootstrapped distribution will be 
computed to assess the strength of mediation. Mediators (M) to be tested are improvements in health 
behaviors and self-efficacy. For example, we will analyze the effect of the intervention on change in maternal 
self-efficacy from baseline to Time 2, and, in turn the effects of this change in maternal self-efficacy at Time 2 
on change in maternal BMI at Time 3.  
 
Sensitivity analyses for Aims 1-3. Site will be included in all the models, and we will look for evidence of 
differential effects across cohort or site. The primary analyses use all available data, but if there is evidence of 
differential missingness by treatment group, we will use imputation methods as a sensitivity analysis.  
 
Aim 4: We will calculate the incremental cost-effectiveness of the intervention, carried out from society’s 
perspective as:  
j
i
j
i
ij
E
E
C
C
CE
−
−
=
 
Where C is cost over the time period of the study; E is effectiveness measured by the outcomes; i refers to the 
intervention and j refers to the control group.  We will calculate cost-effectiveness for the principal outcomes of 
the study; including cost per unit of BMI reduction, and cost per unit of improvement on the nutrition and 
physical activity self-efficacy scales. We will carefully track and calculate the costs of the program intervention 
activities and the control group activities, in order to measure the differences between the costs in the two 
groups. These costs will include hiring interventionists for all aspects of the Healthy Mothers-Healthy  
Children intervention. We will track the time invested in the program by participants in both the intervention and 
control group and calculate the value of time (opportunity cost) relative to the mothers’ average income.  
 
Exploratory Aim: Analyses will be performed on weight status, adiposity, health behavior, and self-efficacy to 
explore whether the intervention effects for mothers are similar for those who are overweight (BMI 25-
29.9kg/m2) and those who are obese (BMI >30 kg/m2). The mixed models described for Aims 1 and 2 will be 
implemented for each of the weight status, adiposity, health behavior, and self-efficacy variables, with the 
addition of four explanatory variables to each model: an indicator for the obese group, the interaction between 
this indicator and the indicator variable for group membership, the interaction between this indicator and time, 
and the three-way interaction among the group indicator, obese indicator, and time. The hypothesis test for the 
three-way interaction as well as the obesity indicator by group indicator interaction jointly equal to zero will 
indicate whether the intervention effects are homogeneous across BMI ranges. For each outcome, differences 
will be calculated to test the effects of the intervention versus control group at each follow-up point separately 
for each BMI range. Similar analyses will be performed with groupings of children in the 25th-84.9th percentile 
(normal weight), 85th-94.9th percentile (overweight) and >95th percentile (obese).  
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1.1           INFORMED CONSENT PROCESS 
10.1.1.2 
CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
10.1.1.3 
CONSENT PROCEDURES AND DOCUMENTATION 
See human subjects section above for details of consent.  

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10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
At the completion of five years or 60 months the study will be closed unless a no cost extension is needed.  
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
See Human Subjects above.  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, the 
safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is extended to the 
data being collected as part of this study. Data that could be used to identify a specific study participant will be 
held in strict confidence within the research team. No personally-identifiable information from the study will be 
released to any unauthorized third party without prior written approval of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, representatives of the 
Institutional Review Board (IRB), regulatory agencies or representatives from companies or organizations 
supplying the product, may inspect all documents and records required to be maintained by the investigator for 
the participants in this study.  
 
The study participant’s contact information will be securely stored at the site for internal use during the study. At 
the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by 
the reviewing IRB, Institutional policies, or sponsor/funding agency requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored on REDCap. This will not include the participant’s contact or identifying information. 
Rather, individual participants and their research data will be identified by a unique study identification number. 
The study data entry and study management systems used by research staff will be secured and password 
protected. At the end of the study, all study databases will be de-identified and archived at the University of North 
Carolina at Chapel Hill School of Nursing. 
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made available to 
the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms used to share data 
will include proper plans and safeguards for the protection of privacy, confidentiality, and security for data 
dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be traceable to a specific study 
participant). Plans for archiving and long-term preservation of the data will be implemented, as appropriate.  
 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has issued 
a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical or other human 
subjects research funded wholly or in part by the federal government.  Recipients of NIH funding for human 
subjects research are required to protect identifiable research information from forced disclosure per the terms 
of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth in 45 CFR Part 

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75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered by this Policy are 
required to establish and maintain effective internal controls (e.g., policies and procedures) that provide 
reasonable assurance that the award is managed in compliance with Federal statutes, regulations, and the terms 
and conditions of award. It is the NIH policy that investigators and others who have access to research records 
will not disclose identifying information except when the participant consents or in certain instances when federal, 
state, or local law or regulation requires disclosure. NIH expects investigators to inform research participants of 
the protections and the limits to protections provided by a Certificate issued by this Policy. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Data collected for this study will be analyzed and stored at the University of North Carolina School of Nursing. 
After the study is completed, the de-identified, archived data will be transmitted to and stored at the University 
of North Carolina School of Nursing, for use by other researchers including those outside of the study.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Medical Monitor or 
Independent Safety Monitor 
Dr. Hudson Santos 
Dr. Mary Lynn 
The University of North Carolina 
at Chapel Hill  
The University of North 
Carolina at Chapel Hill  
Campus Box 7460 
Campus Box 7460 
919-259-4812 
919-966-5450 
hsantosj@email.unc.edu 
Mary_Lynn@unc.edu 
 
See DSMP Above 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of a Data and Safety Monitoring Plan (DSMP) composed of individuals 
with the appropriate expertise. See the DSMP for details.  
 
10.1.7 CLINICAL MONITORING 
 
N/A 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Procedures will be followed according to standard protocols for height, weight, calculation of BMI and BMI 
percentile and collection of anthropometric measurements and questionnaire and accelerometry and 24 hour 
food recall data.  
Quality control (QC) procedures will be implemented as follows: 

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Informed consent --- Study staff will review both the documentation of the consenting process as well as a 
percentage of the completed consent documents.  This review will evaluate compliance with GCP, accuracy, 
and completeness.  Feedback will be provided to the study team to ensure proper consenting procedures are 
followed.  
 
Source documents and the electronic data --- Data will be initially captured on source documents and will 
ultimately be entered into the study database.  To ensure accuracy site staff will compare a representative 
sample of source data against the database, targeting key data points in that review. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described above.  
 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will implement 
corrective actions when the quantity or nature of deviations are deemed to be at a level of concern. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related sites, 
source data/documents, and reports for the purpose of monitoring and auditing by the sponsor/funding agency, 
and inspection by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of the Principal Investigator at the site under the supervision of the 
Project Manager. The investigator will be responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for recording 
data for each participant consented/enrolled in the study.  Data recorded in the electronic case report form 
(eCRF) derived from source documents will be consistent with the data recorded on the source documents.  
 
Clinical data will be entered into REDCap, a 21 CFR Part 11-compliant data capture system provided by the 
University of North Carolina at Chapel Hill. The data system includes password protection and internal quality 
checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
Clinical data will be entered directly from the source documents. 
 
 
 
10.1.9.2 STUDY RECORDS RETENTION  

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Study documents will be retained for a minimum of 5 years.  
10.1.10 
PROTOCOL DEVIATIONS   
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, International 
Council on Harmonisation. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions will be developed by the site and implemented 
promptly.  
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts 
that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical 
Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial 
will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. 
In addition, every attempt will be made to publish results in peer-reviewed journals.  Data from this study may 
be requested from other researchers 5 years after the completion of the primary endpoint by contacting the 
Principal Investigator.   
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, 
is critical. Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation 
in the design and conduct of this trial. The study leadership in conjunction with the NINR has established policies 
and procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest. 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
COC 
Certificate of Confidentiality 

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CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
2 
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Updated to include 3-5 year old 
children 
Increase sample 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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