Reducing Cardiovascular Disease Risk in Perimenopausal Latinas: Pilot Study of a Multi-Component Intervention
Phase: NA
Conditions: Cardiovascular Risk Factor, Health Behavior, Physical Activity, Self Efficacy, Vascular Stiffness
Sponsor: University of North Carolina, Chapel Hill

 
 
Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of 
a Multi-Component Intervention 
 
 
NCT number NCT04313751 
Document Date 08/09/2021 
 

Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of a Multi-Component 
Intervention 
Version 3.000
Protocol  
09 August 2021
NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans – v4.0 2018-12-12 
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Reducing Cardiovascular Risk in Perimenopaual 
Latinas: Pilot Study of a Multi-Component Intervention 
 
Unique Protocol Identification Number:  
National Clinical Trial (NCT) Identified Number: NCT04313751 
 
Principal Investigator: Yamnia Cortes 
Sponsor:  
University of North Carolina at Chapel Hill 
Grant Title: 
Reducing Cardiovascular Risk in Perimenopaual Latinas: 
Pilot Study of a Multi-Component Intervention 
Grant Number:  
1K23MD014767-05 
Funded by:  
National Institute of Minority Health and Health Disparities 
 
Revisions to Version Number: v.1.000 (28 March 2020) 
Version Number: v.2.000 (20 June 2020) 
Version Number: v.3.000 (09 August 2021) 
 
 
Summary of Changes from Previous Version: 
Affected 
Section(s)  
Summary of Revisions Made  
Rationale  
  5.5., 6.0, 8.0 Procedures may be conducted virtually. 
In-person visits for data collection 
should be performed with proper facial 
covering and sanitizing. Prior to 
scheduling visits, research assistants 
must ask about COVID-19 symptoms 
and exposures (see attachment). During 
screening, participants will receive 
information about participating in a 
research study during COVID-19. 
Due to the COVID-19 pandemic we 
have adjusted procedures to reduce 
in-person contact and assess risk of 
COVID-19 exposure. 
  5.0 
The inclusion criteria was updated to 
include women 40-60 years and women 
who are early postmenopausal (1-2 
years since final menstrual period). The 
counties for randomization are Durham 
and Wake versus Orange, Chatham, 
and Alamance. 
We expanded the inclusion criteria to 
increase our community outreach. 
Women that are early postmenopausal 
also experience hormone changes 
and arterial remodeling, which is 
related to increased CVD risk.  
 

Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of a Multi-Component 
Intervention 
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Table of Contents 
Statement of Compliance ............................................................................................. 5 
Investigator's Signature ......................................................................................................... 5 
1 Protocol Summary ..................................................................................................... 6 
1.1 Synopsis ............................................................................................................................ 6 
1.2 Schema .............................................................................................................................. 8 
1.3 Schedule of Activities ....................................................................................................... 9 
2 Introduction .............................................................................................................. 10 
2.1 Study Rationale ............................................................................................................... 10 
2.2 Background ..................................................................................................................... 10 
2.3 Risk/Benefit Assessment ............................................................................................... 12 
2.3.1 Known Potential Risks ............................................................................................................... 12 
2.3.2 Known Potential Benefits .......................................................................................................... 15 
2.3.3 Assessment of Potential Risks and Benefits ............................................................................. 16 
3 Objectives and Endpoints ....................................................................................... 17 
4 Study Design ............................................................................................................ 18 
4.1 Overall Design ................................................................................................................. 18 
4.2 Scientific Rationale for Study Design ........................................................................... 18 
4.3 Justification for Intervention .......................................................................................... 19 
4.4 End-of-Study Definition .................................................................................................. 19 
5 Study Population ...................................................................................................... 20 
5.1 Inclusion Criteria ............................................................................................................. 20 
5.2 Exclusion Criteria ........................................................................................................... 20 
5.3 Lifestyle Considerations ................................................................................................ 20 
5.4 Screen Failures ............................................................................................................... 20 
5.5 Strategies for Recruitment and Retention .................................................................... 20 
6 Study Intervention(s) or Experimental Manipulation(s) ........................................ 22 
6.1 Study Intervention(s) or Experimental Manipulation(s) Administration .................... 22 
6.1.1 Study Intervention or Experimental Manipulation Description .................................................. 22 
6.1.2 Administration and/or Dosing .................................................................................................... 23 
6.2 Fidelity ............................................................................................................................. 23 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING ................................................................... 23 
6.3 Measures to Minimize Bias: Randomization and Blinding .......................................... 23 
6.4 Study Intervention/Experimental Manipulation Adherence ........................................ 24 

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6.5 Concomitant Therapy ..................................................................................................... 24 
6.5.1 Rescue Therapy ........................................................................................................................ 24 
7 Study Intervention/Experimental Manipulation Discontinuation and Participant 
Discontinuation/Withdrawal ....................................................................................... 25 
7.1 Discontinuation of Study Intervention/Experimental Manipulation ........................... 25 
7.2 Participant Discontinuation/Withdrawal from the Study ............................................. 25 
7.3 Lost to Follow-Up ............................................................................................................ 25 
8 Study Assessments and Procedures ..................................................................... 26 
8.1 Endpoint and Other Non-Safety Assessments ............................................................ 26 
8.2 Safety Assessments ....................................................................................................... 27 
8.3 Adverse Events and Serious Adverse Events .............................................................. 27 
8.3.1 Definition of Adverse Events ..................................................................................................... 27 
8.3.2 Definition of Serious Adverse Events ........................................................................................ 28 
8.3.3 Classification of an Adverse Event ............................................................................................ 28 
8.3.4 Time Period and Frequency for Event Assessment and Follow-Up ......................................... 30 
8.3.5 Adverse Event Reporting .......................................................................................................... 31 
8.3.6 Serious Adverse Event Reporting ............................................................................................. 31 
8.3.7 Reporting Events to Participants ............................................................................................... 31 
8.3.8 Events of Special Interest .......................................................................................................... 31 
8.3.9 Reporting of Pregnancy ............................................................................................................. 31 
8.4 Unanticipated Problems ................................................................................................. 31 
8.4.1 Definition of Unanticipated Problems ........................................................................................ 31 
8.4.2 Unanticipated Problems Reporting ........................................................................................... 31 
8.4.3 Reporting Unanticipated Problems to Participants .................................................................... 31 
9 Statistical Considerations ....................................................................................... 32 
9.1 Statistical Hypotheses .................................................................................................... 32 
9.2 Sample Size Determination ............................................................................................ 32 
9.3 Populations for Analyses ............................................................................................... 33 
9.4 Statistical Analyses ........................................................................................................ 33 
9.4.1 General Approach ..................................................................................................................... 33 
9.4.2 Analysis of the Primary Endpoint(s) .......................................................................................... 33 
9.4.3 Analysis of the Secondary Endpoint(s) ..................................................................................... 33 
9.4.4 Safety Analyses ......................................................................................................................... 33 
9.4.5 Baseline Descriptive Statistics .................................................................................................. 34 
9.4.6 Planned Interim Analyses .......................................................................................................... 34 
9.4.7 Sub-Group Analyses ................................................................................................................. 34 
9.4.8 Tabulation of Individual Participant Data ................................................................................... 34 
9.4.9 Exploratory Analyses ................................................................................................................. 34 
10 Supporting Documentation and Operational Considerations ............................ 35 
10.1 Regulatory, Ethical, and Study Oversight Considerations ....................................... 35 
10.1.1 Informed Consent Process ...................................................................................................... 35 
10.1.2 Study Discontinuation and Closure ......................................................................................... 35 
10.1.3 Confidentiality and Privacy ...................................................................................................... 35 
10.1.4 Future Use of Stored Specimens and Data ............................................................................ 36 
10.1.5 Key Roles and Study Governance .......................................................................................... 37 

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10.1.6 Safety Oversight ...................................................................................................................... 37 
10.1.7 Clinical Monitoring ................................................................................................................... 37 
10.1.8 Quality Assurance and Quality Control ................................................................................... 37 
10.1.9 Data Handling and Record Keeping ........................................................................................ 38 
10.1.10 Protocol Deviations ............................................................................................................... 38 
10.1.11 Publication and Data Sharing Policy ..................................................................................... 39 
10.1.12 Conflict of Interest Policy ....................................................................................................... 39 
10.2 Additional Considerations ........................................................................................... 39 
10.3 Abbreviations and Special Terms ............................................................................... 39 
10.4 Protocol Amendment History ...................................................................................... 41 
11 References .............................................................................................................. 42 
 
 

Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of a Multi-Component 
Intervention 
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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. 
INVESTIGATOR'S SIGNATURE 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
 
Date: 3-1-2020 
Name*:  
Dr. Yamnia I. Cortés 
Title*:  
Principal Investigator 
 
 
Investigator Contact Information: 
Affiliation*:  The University of North Carolina at Chapel Hill School of Nursing 
Address:  
Campus Box 7460, Chapel Hill, NC 27599 
Telephone:  919-966-5299 
Email:  
 yicortes@email.unc.edu 
 
 
 

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Intervention 
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1 PROTOCOL SUMMARY 
1.1 SYNOPSIS 
Title: 
Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of a 
Multi-Component Intervention 
Grant Number: 
1K23MD014767-01 
Study Description: 
Cardiovascular disease (CVD) is the leading cause of death among 
Latinas, exceeding rates for Latino men. Evidence suggests that Latinas 
have a significantly worse CVD risk factor profile than non-Hispanic White 
women. Furthermore, Latinas are considerably less likely to meet physical 
activity and dietary guidelines than non-Hispanic White women, particularly 
during perimenopause. Prior studies have shown that increases in CVD 
risk can be prevented in perimenopausal women using a lifestyle dietary 
and physical activity intervention; however, these studies did not include 
Latinas. To address these deficits, the aim of this study is to pilot test a 
multi-component behavioral intervention among perimenopausal Latinas 
(age 40-55) that integrates evidence-based education with physical 
activity, stress management, and coping skills training to: 1) reduce 
biologic CVD risk, including adiposity, blood pressure and arterial stiffness; 
2) improve nutrition, physical activity, and sleep; and 3) improve stress 
management, coping strategies, and self-efficacy. 
Objectives*: 
Primary Objective: 
To examine the feasibility and initial efficacy of the 
multi-component behavioral intervention to reduce 
biologic CVD risk from Time 1 (baseline) to each 
of Time 2 (6 months) and Time 3 (12 months). 
Secondary Objectives: To evaluate the initial efficacy of the intervention 
to improve secondary outcomes of health 
behaviors,  adiposity, inflammatory and stress 
biomarkers, and vasomotor symptoms from Time 
1 (baseline) to each of Time 2 (6 months) and 
Time 3 (12 months). 
Endpoints*: 
Primary Endpoint: 
 
a) Feasibility: enrollment and retention rates; 
barriers and facilitators to enrollment; intervention 
fidelity; suitability of study procedures and 
outcome measures; and participant satisfaction 
with the intervention and study protocol. 
b) Biologic CVD risk: blood pressure, arterial 
stiffness, lipids, blood glucose. 
Secondary Endpoints: a) Health behaviors: nutrition, physical activity, 
sleep, coping strategies. 

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b) Other biological factors: adiposity, inflammatory 
and stress biomarkers, vasomotor symptoms. 
 
Study Population: A total of 80 perimenopausal Latinas. 
Phase* or Stage: 
Cluster randomized controlled with an experimental and wait-list control 
group. 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
Participants recruited from community sites in Durham, Wake, Orange, 
Alamance, and Lee Counties in North Carolina. 
 
Description of 
Study 
Intervention/Experi
mental 
Manipulation: 
 
An experimental group of women receive an intervention consisting of Su 
Corzaón Su Vida education sessions, group physical activity, stress 
management, and coping skills training. The wait-list control group is 
offered the intervention at the end of Time 3 (12 months).  
 
Study Duration*: 
 
A total of 4 years or 48 months. 
 
Participant 
Duration: 
 
Each participant will be in the study a total of 12 months. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.2 SCHEMA 
Flow Diagram 
 
 

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1.3 SCHEDULE OF ACTIVITIES 
Summary of Variables, Measurement, and Data Collection Time Points 
Variables and Measurement 
0 
6 
12 
Feasibility 
    *Process evaluation checklist (bi-monthly) 
    *Screening and enrollment logs 
    *Intervention attendance 
    *Data collection attendance 
     Exit interview 
 
-- 
X 
X 
X 
 
-- 
X 
X 
X 
 
-- 
X 
X 
X 
X 
Biological CVD Risk Factors (Primary Outcomes) 
    Systolic and diastolic blood pressure 
    Fasting blood glucose 
    Fasting lipid profile 
    Arterial stiffness (carotid-femoral PWV) 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Health Behavior (Secondary Outcomes) 
    Nutrition and food security 
    Physical activity questionnaire 
    Accelerometer (7 days, 24 hours/day) 
    Sleep questionnaire 
    Perceived stress 
    Coping response inventory 
    Eating self-efficacy scale 
    Exercise self-efficacy scale 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Biological Influences (Secondary Outcomes) 
    Height, Weight, BMI 
    Waist Circumference 
    Hair Cortisol and Hs-CRP 
    Vasomotor symptoms questionnaire 
 
X 
X 
X 
X 
 
X 
X 
 
X 
 
X 
X 
X 
X 
Demographic, Sociocultural, and Environmental 
    Demographic questionnaire (e.g., age, education) 
    Acculturation questionnaire (e.g., years in US) 
    Everyday discrimination scale 
    Brief resilience scale 
    Health history questionnaire 
    Reproductive history questionnaire 
    Community food assessment 
    Neighborhood risk assessment 
    Physical activity resource assessment 
X 
X 
X 
0 = baseline; 6 = 6-month (completion of intensive intervention and continued support ); 12 = 12-month 
(after 6 months of maintenance on own);  BMI = body mass index; Hs-CRP = high-sensitivity C-reactive 
protein; PVW = pulse wave velocity 
*Completed by Project Manager 
 
 

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2 INTRODUCTION 
2.1 STUDY RATIONALE 
Background: CVD remains the leading cause of death for women globally. In women, risk of 
CVD increases substantially during perimenopause. Latinas have a significantly worse CVD risk 
factor profile than non-Hispanic White women, attributable to several factors including lower 
socioeconomic position, interpersonal violence, discrimination, and stress. These factors are 
related to CVD through their influence on health behaviors as well as potential mechanisms 
involving inflammatory and neuroendocrine pathways. Despite their increased risk, 
however, perimenopausal Latinas remain underrepresented in CVD research. 
  
Methods: This study is guided by the National Institute of Minority Health and Health Disparities 
(NIMHD) Framework, which considers the interplay between sociocultural environment, built 
environment, behavioral influences, and biological influences on health. Using a cluster 
randomized two-group, repeated measures experimental design, the goal of this study is to 
investigate the feasibility and initial efficacy a 12-monthintervention integrating evidence-based 
education and coping skills training with physical activity and stress management. The 
intervention has three phases: 12 weekly sessions (Phase I: education, physical activity, stress 
management, coping skills training) followed by 3 monthly sessions of continued support 
(Phase II); and finally 6 months of skill maintenance on their own (Phase III). Measurement 
visits will occur at baseline, 6, and 12 months. We will conduct in-depth exit interviews with 
participants to assess barriers and facilitators to recruitment and enrollment, delivery of the 
intervention, fidelity, and suitability of assessment procedures. We will partner with local 
churches and community centers in two counties to recruit participants and deliver the 
intervention. Data will be collected at Time 1 (0 months [baseline]) to Time 2 (6 months 
[completion of the intervention]) and Time 1 to Time 3 (12 months [after 6 months with no 
contact from the study staff]). Data collected will include blood pressure, lipid profile, blood 
glucose, and arterial stiffness. Secondary outcomes will include health behaviors and self-
efficacy, adiposity, inflammatory and stress biomarkers, and vasomotor symptoms.  
  
Discussion: This study will contribute to knowledge on the feasibility of behavioral interventions 
including stress management and coping skills training delivered by CHWs, which could reduce 
CVD burden among perimenopausal Latinas. 
2.2 BACKGROUND 
CVD, including coronary heart disease and stroke, is the leading cause of death among Latinas 
(29%), exceeding rates for Latino men (27%) [1]. Despite being at greater risk for CVD, only 
34% of Latinas are aware that CVD is the leading cause of death in women [2]. Although 
several national organizations have developed initiatives to raise understanding about CVD 
among Latinas, as yet Latinas remain considerably less likely to meet physical activity and 
dietary guidelines than non-Hispanic White women, particularly during perimenopause [3]. 
Perimenopause is marked by dramatic changes in sex hormone levels, which may adversely 

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affect CVD risk factors such as body fat, insulin secretion, and lipoprotein levels [4,5]. 
Perimenopausal Latinas have lower estrogen and higher follicle stimulating hormone levels than 
non-Hispanic White women [6],which can increase the risk for CVD. Thus, perimenopause is a 
critical window for CVD prevention among Latinas. 
  
The sociocultural environment includes beliefs, customs, and values of a population. The 
sociocultural environment of perimenopausal Latinas may include poverty and limited English 
proficiency, both of which are associated with lower healthcare access [6,7].Studies among 
women age 40-65 years have shown that chronic stress, job strain, and discrimination may 
increase biologic CVD risk through their influence on health behaviors [8,9]. Latinas are 
particularly at risk for CVD during perimenopause because they may experience acculturative 
stress and social isolation, resulting in adverse health behaviors such as increased 
sedentariness [10,11]. This study addresses the sociocultural environment by providing peer 
education using community health workers (CHWs), support, and resources to improve Latinas’ 
health in context of their everyday lives. Peer education using CHWs has been shown to 
improve diet, physical activity, and weight [12]. 
  
The built environment encompasses all buildings, spaces, and structures where individuals live, 
work, and play [13]. This study focuses on the neighborhood-level built environment, including 
accessibility to safe parks/recreation areas and supermarkets or produce grocers. 
Disadvantaged neighborhoods have a high concentration of poverty and unemployment, which 
influences crime rates, availability of public services, parks, grocery stores, and fast food and 
liquor establishments [14]. Many Latinas live in neighborhoods with only 32% as many grocery 
stores as less disadvantaged communities and thus lack access to healthy food [15]. Living in 
disadvantaged and unsafe neighborhoods increases stress [16], limits physical activity and 
increases sedentary behavior [17,18], which influence biologic CVD risk factors such as blood 
pressure, cholesterol, adiposity and inflammation [19,20]. To address the built environment, our 
intervention will provide women with information on where to access healthy low-cost food and 
safe spaces for physical activity. 
  
The most consistent behavioral factors contributing to CVD risk during perimenopause are 
inadequate nutrition, decreased physical activity [21], poor sleep patterns [22], and chronic 
stress [23]. Social cognitive theory [24] posits that enhancing an individual’s knowledge and 
skills to perform a new behavior improves self-efficacy, which in turn increases likelihood that 
the new behavior will be maintained. National reports have shown that <16% of adult Latinas 
consume the recommended servings of whole grains, fruits, and vegetables [25]. The Hispanic 
Community Health Study/Study of Latinos has reported that only 27% of Latinas age 45-64 
years meet the national guidelines for physical activity [26]. In addition, over half of 
perimenopausal Latinas report difficulty sleeping [27], which has been associated with arterial 
stiffness [28], a hardening of the vessel wall often predictive of CVD [29]. Latinas report higher 
levels of perceived stress compared to perimenopausal women of any other race/ethnicity in the 
US [30]. In this study, we will facilitate behavioral change and improve self-efficacy in 
perimenopausal Latinas by helping them acquire coping strategies for problem-solving, 
communication, stress management, and cognitive behavioral modification. 

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Prior interventions have been successful in increasing knowledge of CVD risk, physical activity, 
and heart-healthy diet among Hispanics/ Latinos [31,32]. Many of these interventions have 
incorporated an evidence-based CHW-led curriculum—Su Corazón, Su Vida (SCSV)—a 12-
lesson curriculum consisting of information on CVD risk awareness, healthy food choices, and 
physical activity [33]. The curriculum has been used among Latinos age 18 and older in the US 
and Mexico, with success in improving health behaviors [31,32]. Most interventions 
incorporating SCSV, however, have been education only, with either a short follow-up (<6 
months) [31] or no assessment of biologic CVD risk [33]. Our study will address important 
limitations of prior interventions. We will pilot test a novel multi-component behavioral 
intervention integrating evidence-based education (SCSV) with coping skills training, physical 
activity sessions, and stress management. This is a new multi-component intervention to reduce 
biologic CVD risk (blood pressure, arterial stiffness, lipids, blood glucose) and to improve health 
behaviors (nutrition, physical activity, sleep, coping strategies, self-efficacy,  stress 
management) among perimenopausal Latinas. 
2.3 RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS 
  
Risks to Human Subjects 
Institutional Review Board (IRB) approval was obtained from The University of North Carolina 
at Chapel Hill (UNC-CH). Using a cluster randomized two-group, repeated measures 
experimental design, the goal of the study is to investigate the feasibility and initial efficacy of a 
12-month intervention consisting of: Phase I) 12-week nutrition and exercise education, physical 
activity group sessions, coping skills training, and stress management intervention in 
perimenopausal Latinas; Phase II) 6 months of continued monthly contact to help women 
improve health behaviors and self-efficacy; and Phase III) 6 months of health maintenance 
without contact from study staff. We will partner with community centers to enroll women and we 
will partner with two churches in two North Carolina counties to deliver the intervention. 
  
Inclusion criteria include age 40-60 years; self-identify as Latina; understand spoken English or 
Spanish; perimenopausal (menstrual bleeding in the past three months, but timing of periods 
have varied in past year, or no menstrual bleeding in the past 3-11 months) or early 
postmenopausal (1-2 years since final menstrual period); intact uterus and at least one ovary; 
not currently pregnant; no hormone therapy or oral contraceptives in the past three months. 
Potential participants will fill out a health history questionnaire to ascertain if they have a history 
of CVD (heart attack, stroke, coronary heart disease), heart murmur, congenital heart disease, 
family history of sudden death, difficulty walking or exercising. Women who answers yes to any 
of these health history questions will be excluded from the study and referred to a health care 
provider. After enrollment and baseline assessment, two churches in two counties will be 
randomly assigned to either the intervention or control group. Participants will be assigned to 
the group in their respective county. Participants will be informed of their group assignment by 
telephone. 

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Data will be collected at Time 1 (baseline [0 months]), Time 2 (post Intensive Intervention 
and Continued Support [6 months]), and Time 3 (6 months after completion of Continued 
Support [12 months]). Data collected will include the primary outcomes of blood pressure, 
arterial stiffness based on carotid-femoral pulse wave velocity measures, lipid profile (total 
cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), blood 
glucose; secondary outcomes of health behaviors  (Sleep Quality Questionnaire, Food Behavior 
Checklist, Physical Activity Questionnaire, and 7-day Accelerometer), self-efficacy (Eating Self-
Efficacy Scale and Exercise Self-Efficacy Scale), body mass index, waist circumference, hs-
CRP, hair cortisol, and vasomotor symptoms. We will also evaluate the feasibility of the study 
including, number of eligible participants; methods of identifying/recruiting participants; 
willingness of participants to be randomized; practicality of delivering the intervention in the 
proposed setting; enrollment and retention rates, and suitability of the intervention and 
assessment protocol. Data analysis will use descriptive statistics and general linear mixed 
models to test the hypotheses. Both intervention and control group participants will each receive 
$120 for their time during data collection visits ($35 at Time 1, $40 at Time 2, $45 at Time 3) 
and $5 to help with transportation costs each time they come to class or data collection visit. 
  
Participants in the intervention group will receive a 12-week Intensive Intervention (Phase I) with 
weekly 2-hour sessions consisting of 60 minutes of nutrition and exercise education and coping 
skills training, a 45-minute physical activity class, and 15-minute stress management session. 
During Continued Support (Phase II), participants will meet monthly for 3 months for 60 minutes 
of classroom discussion regarding problems they are having with nutrition and physical activity. 
Data collection in the wait-list control group will occur at the same time intervals as women in 
the intervention group. Following the last data collection, we will offer Phase I of the intervention 
to women in the wait-list control group. 
  
Participants will be tracked using ID numbers. Designated research staff will collect, gather, and 
enter data into a REDCap database with built-in range checks and skip patterns. The Project 
Coordinator/Senior Research Assistant with double-check 20% of data entry against the raw 
data for quality assurance. 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 woman in the intervention 
group attend 12 classes for 120 minutes. During Continued Support women will meet monthly 
for 3 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. Women in the wait-list control group will be offered the Intensive Intervention at the 
end of the 12-month follow-up. 
  

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As a part of the first data collection after women consent to enroll in the study, they will 
complete an interviewer-administered survey in their preferred language (English, 
Spanish).  Women will have their height, weight, waist circumference, and blood pressured 
measured by a bilingual research assistant in a private room. Trained research assistants will 
also collect carotid-femoral pulse wave velocity measures, a blood sample by venipuncture, and 
a sample of hair for cortisol assessment. 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 participants. No more than minimal risks are anticipated from this study and these 
potential risks are related to the intervention, a breach of confidentiality, physical measures, and 
venipuncture. 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. 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 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 in this study. 
  
Adequacy of Protection against Risks 
Dr. Cortés has extensive experience working with Hispanic/Latino women and Co-Mentors/Co-
Investigators, Drs. Berry and Perreira have strong relationships with the study sites. To assure 
that we meet enrollment targets, all project staff will be bilingual and all recruitment and 
intervention materials and instruments will be bilingual (English and Spanish). Two months 
before enrollment, the bilingual Project Coordinator will give a presentation to staff at community 
centers in two counties in North Carolina and place English and Spanish language flyers and 
brochures in each. The project coordinator will screen potential participants by phone. If a 
woman meets inclusion criteria and is interested in participating, we will schedule an 
appointment at a convenient time at the participant’s home or community site to confirm 
eligibility and obtain informed consent. Written consent will be obtained by a bilingual research 
assistant using appropriate Informed Consent forms approved by the institutional review board 
of the University of North Carolina at Chapel Hill. Informed Consent forms will be available in 
English and Spanish. Potential participants are assured that participation is voluntary and that 
refusal to participate will not influence their health care or position in their community. All 
participants will be provided with instructions on how to contact the investigative team if any 
problems or concerns arise. Data will be collected only from subjects who have agreed to 
participate in the study. Consents will be stored in locked file cabinets in the research office, 
separate from any study data. All participants will be adults age 40-55 years. 
  
Risks will be minimized by study procedures that safeguard privacy. Personal Identifying Health 
Information (PHI) will be stored on password-protected lap top computers, with only a subject 
study number as an identifier. The key linking participants’ PHI to their data will be kept in a 
separate file on a secure server, and destroyed at the conclusion of the study.  Data will be 

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recorded on forms on which the only identifier is a research ID code. Only the PI and project 
coordinator have access to the link between the research ID code and PHI. No names or 
identifying information will be included in research reports. Subjects' names will not appear on 
questionnaires. While data collectors are in the home, any previously completed surveys for 
data collection forms will be kept in a secure place, such as the trunk of a car, until they can be 
delivered to the research office for data entry where they will be kept in a locked file cabinet. 
Codes will be used to identify the nursing home and all individual subjects. All computers 
housing research data have passwords and timed screen savers requiring a password for 
access. All team members who have contact with data will complete training sessions on proper 
and secure ways to handle sensitive information and how to handle computing environments in 
general. In addition, no individually identifiable information will be included in disseminated 
findings; study results will be reported in aggregate only. 
  
To minimize potential participant burden, (a) we have limited the total number of contact hours 
required in the intervention; (b) we will deliver the intervention in a space near the participants’ 
home; c) physical activity sessions will be led by a bilingual physical activity interventionist 
certified by the American College of Sports Medicine; and (d) we will complete data collection at 
the participants’ home and provide incentives. If any participant has a physical injury, we will 
help them seek immediate medical attention. If at any time any participant voices concern to the 
study staff that they are fatigued or do not want to continue, they will be encouraged to stop and 
return to the next class. 
  
Potential risks of the physical measures, venipuncture, and hair cortisol along with specific 
strategies for minimizing risk, will be discussed with each participant during the informed 
consent process and at each data collection period. Risks will be minimized by using bilingual 
trained RAs, a standardized protocol, and phlebotomists who follow proper technique. Provision 
for medical treatment, should it be required, is included in the written informed consent; each 
patient receives a copy. Women can stop at any time or refuse to complete any measure and 
that will not affect their ability to continue in the study. 
2.3.2 KNOWN POTENTIAL BENEFITS 
  
Potential Benefits of the Proposed Research to Human Subjects and Others 
Participants. Participants have the potential to benefit from improved CVD risk awareness and 
health behaviors (e.g., nutrition, physical activity, coping strategies, self-efficacy). They may 
receive some psychological benefit from stress management sessions and learning coping skills 
such as problem-solving. Participants may also benefit from the study my decreasing their 
biologic CVD risk (i.e., blood pressure, arterial stiffness, weight, waist circumference). 
  
Others/Community. The proposed research has potential public health benefits because 
Hispanic/Latinos are the largest ethnic minority in the United States. Progress regarding CVD 
risk among perimenopausal Latinas may lead to significant improvement in the overall CVD 
burden in the US. 

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2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
  
See 2.3.1 above for assessment of potential risks and benefits 

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3 OBJECTIVES AND ENDPOINTS 
Primary Objective: To examine the feasibility and initial efficacy of the multi-component 
behavioral intervention to reduce biologic CVD risk from Time 1 (baseline) to each of Time 2 (6 
months) and Time 3 (12 months). 
  
Secondary Objective: To evaluate the initial efficacy of the intervention to improve health 
behaviors,  adiposity, inflammatory and stress biomarkers, and vasomotor symptoms from Time 
1 (baseline) to each of Time 2 (6 months) and Time 3 (12 months). 
  
Primary Outcomes: 
   Systolic and diastolic blood pressure 
   Carotid-femoral pulse wave velocity 
   Total cholesterol 
   High-density lipoprotein 
   Low-density lipoprotein 
   Triglycerides 
   Fasting blood glucose 
   Enrollment and retention rates 
   Intervention attendance 
   Participant satisfaction with the intervention and study protocol 
  
Secondary Outcomes: 
   Health behaviors (nutrition, physical activity, sleep) 
   Self-efficacy (eating and exercise) 
   Adiposity (weight, body mass index, waist circumference) 
   High-sensitivity C-reactive protein 
   Hair cortisol 
 
Other Outcomes: 
   Vasomotor symptoms 
  

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4 STUDY DESIGN 
4.1 OVERALL DESIGN 
This study will use a cluster randomized repeated measures study design with two groups to 
evaluate the feasibility and initial efficacy of the intervention with 80 perimenopausal 
Latinas. The intervention group (n=40) will receive a 3-phased intervention. In Phase I 
(Intensive Intervention), bilingual community health workers will meet with women in small 
groups to deliver 12 weekly (3 months) 2-hour sessions including education, group physical 
activity, stress management, and coping skills training. Phase II (Continued Support) consists of 
3 monthly 1-hour sessions led by community health workers to problem-solve issues related to 
nutrition and exercise, stress management, and to provide feedback and support. During Phase 
III (Follow-up), participants are expected to maintain skills on their own for 6 months. Data will 
be collected at baseline (Time 1), completion of Phase II (Time 2, 6 months after baseline), and 
after completion of 6 months on their own (Time 3, 12 months after baseline).  Data in the wait-
list control group (n=40) will be collected at the same time intervals as the intervention group. 
After Time 3 data collection, they will be offered the Intensive Intervention (12 weekly sessions). 
Both groups will receive reminders a week prior to each data collection visit and a monthly 
"thank you" card for their continued participation. 
  
Data will be collected at Time 1 (0 months [baseline]), Time 2 (6 months [completion of the 
intervention]) and Time 3 (12 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 initial efficacy after participants have had 
sufficient time to implement their new nutrition, physical activity, and coping skills on their own. 
We will assess feasibility using questionnaires at Time 3, as well as process evaluations and 
attendance logs. We chose these times because 6-to-12 months after completion of an 
intervention is a standard interval for follow-up in behavioral interventions during perimenopause 
[34].  
4.2 SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Preliminary studies have demonstrated that perimenopause is an important time to implement 
behavioral interventions for the prevention of CVD. While behavioral interventions have been 
shown to increase CVD risk awareness and knowledge of heart-healthy behaviors (e.g., 
diet  and exercise) among Hispanics/Latinos [31,32], most interventions among Latinas have 
been education only with either a short follow-up (<6 months) [31] or no assessment of biologic 
CVD risk [33]. Additionally, although studies among non-Hispanic White and Black women have 
shown that dietary and physical activity interventions can slow the progression of subclinical 
atherosclerosis during perimenopause [35], no such interventions have focused on 
perimenopausal Latinas. Our study will address important limitations of prior interventions. We 
will pilot test a novel multi-component behavioral intervention integrating evidence-based 
education - SCSV curriculum [36] - with coping skills training developed and tested by Co-
Investigator Dr. Berry  [37], physical activity sessions, and stress management. Thus, this is a 

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novel multi-component intervention to reduce biologic CVD risk (blood pressure, arterial 
stiffness, lipids, blood glucose) and to improve health behaviors (nutrition, physical activity, 
sleep, coping strategies, self-efficacy,  stress management) among perimenopausal Latinas. 
4.3 JUSTIFICATION FOR INTERVENTION 
Risk of CVD increases substantially during perimenopause. Perimenopausal Latinas remain 
considerably less likely than non-Hispanic White women to meet physical activity and dietary 
guidelines, or be aware that CVD is the leading cause of death among women. In North 
Carolina and throughout the US Latinas often live in a sociocultural environment of poverty, 
have limited English proficiency, and face social isolation and discrimination [37]. Latinas often 
reside in built environments that may further contribute to CVD risk due to limited access to 
affordable healthy food options and safe public spaces for physical activities [38]. We will collect 
data on the sociocultural and built environment to tailor the intervention, and intervene on the 
behavioral influences of cardiovascular health (i.e., nutrition, physical activity, sleep, stress 
management, coping strategies and self-efficacy) to decrease biologic CVD risk among 
perimenopausal Latinas. Community health worker-led behavioral interventions among Latinos 
have been successful in improving health behaviors [31,32], although reduction of biologic CVD 
risk has been inconsistent [31,39]. Importantly, prior interventions have not targeted 
perimenopausal Latinas specifically or examined arterial stiffness, an independent predictor of 
CVD events [29]. Furthermore, these interventions have not incorporated physical activity, 
stress management, and coping strategies, essential components to reduce CVD risk among 
perimenopausal Latinas. To address these deficits, this 12-month multi-component behavioral 
intervention integrates evidence-based education and coping skills training with physical activity 
and stress management to 1) reduce biologic CVD risk, including arterial stiffness; and 
2) improve secondary outcomes of health behaviors, adiposity, inflammatory and stress 
biomarkers, and vasomotor symptoms. 
4.4 END-OF-STUDY DEFINITION 
A participant is considered to have completed the study if she has completed Time 1 (baseline), 
Time 2 (6 months) and Time 3 (12 months) data collection. 

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5 STUDY POPULATION 
5.1 INCLUSION CRITERIA 
Inclusion criteria are: age 40-55 years; self-identify as Latina; understand spoken English or 
Spanish; perimenopausal based upon the Study of Women's Health study definitions [40]: 
menstrual bleeding in the past three months, but timing of periods have varied in past year, or 
no menstrual bleeding in the past 3-11 months; intact uterus and at least one ovary; not 
currently pregnant; no hormone therapy or oral contraceptives in the past three months (as 
these may alter bleeding patterns). These eligibility criteria are consistent with previous 
observational studies and clinical trials in perimenopausal women [41] and are standard to 
clearly assess menopausal status in midlife women. 
5.2 EXCLUSION CRITERIA 
Exclusion criteria are: history of CVD (heart attack, stroke, coronary heart disease), impaired 
physical mobility, or difficulty exercising. Women will not be excluded if on current anti-
hypertensive, lipid-lowering, or diabetes medications.  
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 
This study builds on established partnerships between UNC-CH, local churches, and community 
centers in Orange County and Durham County. Dr. Diane Berry and Dr. Krista Perreira have 
extensive experience working with these communities in prior studies, and will guide my 
community engagement. To assure that we meet enrollment targets, all project staff will be 
bilingual (English, Spanish) and all study materials (recruitment, intervention, and instruments) 
will be available in Spanish. Participants will be recruited by a Community Health Worker (CHW) 
and Research Assistant (RA) from local churches, and community centers in Orange County 
and Durham County. Two months before enrollment, the Project Coordinator will meet with staff 
at the churches and community centers to confirm recruitment strategies and place Spanish 
language flyers with information about the study and eligibility criteria in the entrance and 
common areas. The flyers will contain a phone number for individuals to call if they’re interested 
in participating in the study. Additionally, the CHW and RA will be available weekly after church 
services and monthly at events organized by community centers. RAs will record the names and 

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telephone numbers of interested women privately and schedule them for a phone screening. 
This approach worked well in prior studies that enrolled 56 women in over a month [42]. We 
plan to enroll 8-10 women per week and can extend the timeline for enrollment if needed. If we 
have difficulty enrolling participants we will ask community leaders from the recruitment sites for 
advice. The Project Coordinator will conduct a phone screening, asking women for their 
birthdate, last menstrual period, regularity of menstrual periods, history of hysterectomy or 
oophorectomy, use of hormone therapy or birth control pills, and history of CVD. Women who 
meet the study criteria will be scheduled for a baseline visit to confirm eligibility, review the 
study, requirements of participants, and the risks and benefits of participating, random 
assignment and answer questions. Data collection will occur in a private location in the 
participant’s home (approximately 90 minutes). We have time in the schedule for make-up data 
collections. 
       
Procedures for Minority Retention and Challenges 
To strengthen retention, our intervention sessions will be interactive, with culturally-tailored 
content developed to engage and sustain participants’ interest (Su Corazón, Su Vida curriculum 
and coping skill training). Women who miss a learning session will be offered an opportunity to 
review the weekly class content over the phone, and will be reminded when the next class will 
be held. We will provide women with handouts including tips, a list of resources, recipes, and 
illustrations in Spanish on how to improve their nutrition, physical activity, and sleep.  We will 
ask participants for phone numbers of family members and permission to call them if we cannot 
contact them. We will be flexible in scheduling enrollment and data collection appointments and 
send thank you cards. We will remind participants of their data collection visits one week before 
and confirm the day before the appointment. Participants in both groups will receive $35 after 
the baseline visit, $40 after the 6-month visit, and $45 after the 12-month data collection. These 
approaches have been successful in prior studies with Latinas, with <20% attrition [43]. We will 
make every effort to keep our attrition lower than 20%; if attrition exceeds 20%, we will contact 
the participants to ask why they stopped coming and develop strategies to assist them to 
continue in the study if they wish. We will also meet with our Community Advisory Board to 
develop and implement strategies to improve retention. 
  
 
 

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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 
The intensive intervention consists of 12 weekly bilingual (English, Spanish) sessions that 
include 60 minutes of interactive learning, 45 minutes of physical activity, and a 15-minute 
stress management session. The first 8 sessions will integrate education from SCSV related to 
CVD risk awareness, healthy food choices, physical activity, blood pressure control, and 
diabetes. To enhance the relevance of the curriculum to perimenopause, we will include 
messages from American Heart Association Go Red Por Tu Corazón. Each week CHWs will 
give participants a SCSV or AHA Go Red Por Tu Corazón handout with information on healthier 
meals and increasing daily physical activity. In the remaining four learning sessions of Phase I, 
we will integrate previously tested and acceptable coping skills training sessions (i.e., goal-
setting, problem-solving, cognitive restructuring, conflict resolution, assertiveness training) with 
a focus on barriers for perimenopausal Latinas. Trained bilingual CHWs will deliver learning 
sessions and 15-minute stress management sessions in groups of 20 participants. 
  
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. A bilingual physical activity interventionist certified 
by the American College of Sports Medicine will teach the physical activity classes and reinforce 
ways to increase physical activity and decrease sedentary behaviors. At baseline, we will give 
participants an accelerometer and the RA will train them in its use as part of the intervention. 
The intervention group will be encouraged to increase their physical activity weekly by small 
increments until they are averaging 10,000 steps a day or 150 minutes per week; this group will 
also be provided information on the sociocultural and built environments such as a list of 
grocers where they can access healthy affordable food and free or low-cost spaces to exercise 
(e.g., YWCA/YMCA) close to home. Missed physical activity sessions will not be made up, but 
participants can make up learning and stress management sessions. 
  
Continued Support  
During Continued Support, participants will return to the church for classes once a month for 3 
months. As a part of the intervention, participants engage in a discussion run by the bilingual 
CHW, who will help women solve problems they have encountered related to nutrition and 
physical activity for 60 minutes and then receive a 45 minute physical activity class and 15-
minute stress management session. If a participant misses a class, the bilingual interventionist 
will call and ask how the woman doing and give the date of the next class. Continued support 
classes will not be made up. 
  

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Wait-List Control Group 
Data will be collected from the wait-liste control group at Time 1, Time 2, and Time 3; and 
participants will receive up to $120 for their participations ($35 at Time 1, $40 at Time 2, and 
$45 at Time 3) in addition to a $5 transportation voucher at each data collection. The wait-list 
control group will receive a "thank you" postcard for their continued participation. Participants 
will receive a accelerometer and log book after they have completed Time 3 data. At that time, 
the wait-list control group (the cluster) will also be offered  the intervention classes in the 
church.  In addition the monthly "thank you" cards, participants will be called several days 
before classes and data collection to remind them.  
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 [44]. For category one, treatment design, the intervention and control group 
condition is clearly defined and participants will receive the same duration of contact over time. 
The CHWs 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 using a standardized manual and teach back the intervention to the PI. For category 
three, delivery, the bilingual project coordinator will observe two randomly selected sessions 
per month using a checklist to score delivery based on pre-identified content. We define fidelity 
as delivering >80% of the protocol content. If drift occurs, the PI will retrain CHWs until the 
protocol is followed consistently. CHWs will collect data on attendance, reasons for absence, 
and make-up learning sessions provided. For category four, receipt, interventionists will ask 
questions and generate discussion during each learning sessions to assess the degree to which 
participants understand the content and participants will be asked to set a goal based on the 
information reviewed during the learning session. CHWs will evaluate category five, 
enactment,  during the 3 monthly continued support sessions by discussing changes in diet, 
physical activity, number of steps taken per day, and stress management; RAs will also assess 
enactment during exit interviews at Time 3 with participants. 
6.3 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
After enrollment and baseline assessment, the two churches will be randomized to either the 
intervention or wait-list control group using a computer-generated randomization table. 
Participants will be informed of their group assignment by telephone. Data collection research 
assistants will be blinded to group status. 

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6.4 STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
See 6.2.1 for details 
6.5 CONCOMITANT THERAPY 
N/A 
6.5.1 RESCUE THERAPY 
  
N/A 
  
 
 

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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. 
Participants 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 study file. 
  
Should the participant continue to be unreachable, she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
  
 
 

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8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
Summary of Variables, Measurement, and Data Collection Time Points 
Variables and Measurement 
0 
6 
12 
Feasibility 
    *Process evaluation checklist (bi-monthly) 
    *Screening and enrollment logs 
    *Intervention attendance 
    *Data collection attendance 
     Exit interview 
 
-- 
X 
X 
X 
 
-- 
X 
X 
X 
 
-- 
X 
X 
X 
X 
Biological CVD Risk Factors (Primary Outcomes) 
    Systolic and diastolic blood pressure 
    Fasting blood glucose 
    Fasting lipid profile 
    Arterial stiffness (carotid-femoral PWV) 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Health Behavior (Secondary Outcomes) 
    Nutrition and food security 
    Physical activity questionnaire 
    Accelerometer (7 days, 24 hours/day) 
    Sleep questionnaire 
    Perceived stress 
    Coping response inventory 
    Eating self-efficacy scale 
    Exercise self-efficacy scale 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Biological Influences (Secondary Outcomes) 
    Height, Weight, BMI 
    Waist Circumference 
    Hair Cortisol and Hs-CRP 
    Vasomotor symptoms questionnaire 
 
X 
X 
X 
X 
 
X 
X 
 
X 
 
X 
X 
X 
X 
Demographic, Sociocultural, and Environmental 
    Demographic questionnaire (e.g., age, education) 
    Acculturation questionnaire (e.g., years in US) 
    Everyday discrimination scale 
    Brief resilience scale 
    Health history questionnaire 
    Reproductive history questionnaire 
    Community food assessment 
    Neighborhood risk assessment 
    Physical activity resource assessment 
X 
X 
X 
0 = baseline; 6 = 6-month (completion of intensive intervention and continued support ); 12 = 12-month 
(after 6 months of maintenance on own);  BMI = body mass index; Hs-CRP = high-sensitivity C-reactive 
protein; PVW = pulse wave velocity 
*Completed by Project Manager 
 
 

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8.2 SAFETY ASSESSMENTS 
N/A 
8.3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
  
Definition, Expected Risks, and Potential AEs. An adverse event (AE) is any untoward 
medical occurrence in a participant during the clinical study, which does not necessarily have a 
causal relationship with the intervention. An AE may include: 1) any new signs or symptoms; 2) 
any new illness or disease or deterioration of an existing condition; and 3) any clinically 
significant abnormal laboratory assessments or clinical tests. Additionally, per UNC-CH’s policy 
all participant deaths, protocol deviations, complaints about the research, and breaches of 
confidentiality are reportable AEs. A serious adverse event (SAE) is any AE that results in one 
or more of the following outcomes: death, a life-threatening event, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a 
serious medical event. 
  
Identifying AEs. Potential risks identified for participants are outlined in the Protection of 
Human Participants section and will also be outlined in the IRB approved informed consent 
document. Participants will be queried about the occurrence of AEs at each visit. They will also 
be instructed to phone at any time during the study with an AE. The PI will work with the Safety 
Officer to develop a system to test whether abnormalities are equally distributedbetween the 
intervention and control groups. Data will be presented to the Safety Officer if a significant 
increase inabnormalities is noted. The Safety Officer will provide the PI with recommendations 
regarding problems that wouldrequire modification for safety reasons. 
  
Reviewing and Reporting AEs. AEs will be reviewed by the Safety Officer and determined to 
be mild (no interference in usual activities); moderate (some interference in usual activities); or 
severe (usual activities were significantly interrupted).  AEs will be categorized according to the 
likelihood that they are related to the study intervention. The Safety Officer will rate the 
assessment of attribution to the study as not related, unlikely, possible, probable, or definite to 
the intervention. 
  
The PI will be responsible for ensuring that all AE and SAEs are reported to the Co-Mentors, 
scientific advisors, Senior RA, Safety Officer, the IRB and NIH/NIMHD within 3-7 days. An 
incident report will be created within 24 hours and sent by electronic email by the PI to the Co-
Mentors, scientific advisors, Senior RA, Safety Officer, the IRB and NIH/NIMHD. The PI will 
follow-up with the participant and will prepare a report. The AEs will be reviewed every three 
months by the Co-Mentors, scientific advisors, the Senior RA, Safety Officer, and the PI, and a 
report prepared for the Human Participants Committee and the NIH/NIMHD. Process notes will 
be kept concerning any decisions. 
  

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Any SAE or deaths that occur during the study will be reported by telephone immediately to the 
Co-Mentors, scientific advisors, the Senior RA, Safety Officer, the IRB and NIH/NIMHD. An 
incident report will be sent by electronicmail by the PI to Co-Mentors, scientific advisors, the 
Senior RA, Safety Officer, the IRB and NIH/NIMHD within 24 hours. The PI will follow-up 
immediately with the participant to investigate and prepare a report for all members of 
theHuman Participants Committee and comply with all regulations regarding the reporting of 
SAEs. The PI will beresponsible for complying with all regulations concerning the reporting of a 
SAE and will prepare a full report forNIH/NIMHD. The PI will meet with the Co-Mentors, 
scientific advisors, and the Senior RA and seek input from the Program Officer. Process notes 
will be kept concerning any decisions. 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
  
See 8.3.1 above 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
  
See 8.3.1 above 
8.3.3.1 SEVERITY OF EVENT 
  
See 8.3.1 above 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL 
MANIPULATION 
  
Study Overview: 
The overall goal of this project is to determine whether a multi-component intervention 
consisting of education and physical activity sessions, stress management, and coping skills 
training will decrease biologic cardiovascular risk (blood pressure, arterial stiffness, lipids, blood 
glucose) among perimenopausal Latinas. The DSMP outlined below 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 Minority 
Health and Health Disparities (NIMHD). 
  
Monitoring Entity: 
Principal Investigator (PI) and IRB. Oversight and monitoring of the conduct and progress of 
the study will be provided by the PI with delegation of responsibilities to designated study 
personnel, and the Institutional Review Board (IRB) of UNC. They will ensure all entry criteria 
are met prior to the initiation of the protocol and all study procedures and reporting of adverse 
events is performed according to the IRB-approved protocol. The PI will report adverse events 
to the Safety Officer, IRB, and funding agency. 
 

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Independent Safety Officer. We will appoint a Safety Officer with both clinical and intervention 
research expertise to provide quarterly safety monitoring throughout the conduct of the 
study.  The Safety Officer will be independent from the study team.  The Safety Officer will 
review the protocol, intervention components, and all data collection processes prior to study 
implementation. The Safety Officer will review interim data, all reports of adverse events 
quarterly, and, when necessary, issue recommendations to the PI regarding the continuation, 
modification, or termination. 
  
Data Quality and Safety Review Plan and Monitoring: 
Subject Accrual and Compliance with Inclusion/Exclusion. 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. 
  
Participant Compliance to the Intervention. Data on compliance to the intervention will be 
collected weekly by the senior RA and reviewed quarterly by the Co-Mentors, scientific advisors, 
the Senior RA, Safety Officer, and PI. Compliance on the part of participants will be evaluated 
by attendance and process evaluation as outlined in the study. If intervention attendance drops 
below 80%, participants 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 Co-
mentors, scientific advisors, and the Safety Officer to discuss methods for improving 
compliance. 
  
Study Visits and Data Collection. The PI and Dr. Crandell (Study Statistician) will oversee and 
train the senior RA 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, concurrent, 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. Data entry and 
monitoring will be completed in REDCap, 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. Dr. Crandell will oversee the development of the REDCap database and train RAs 
how to compare data entry against source data and make corrections as needed. Dr. Crandell 
will develop a data dictionary to support accurate data entry between RAs and a data log book 
will be created to establish an audit trail for compliance. 
  
Ongoing quality control procedures will be implemented for data collection, storage and 
processing. The senior RA will conduct monthly monitoring of the study database and generate 

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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. 
8.3.3.3 EXPECTEDNESS 
  
N/A 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
  
The frequency of event assessment and follow-up for this study is summarized in the table 
below. 
Frequency of Data Review  
Data Type 
Frequency of 
Review 
Reviewer 
Subject accrual (including compliance with 
enrollment criteria) 
Monthly 
Co-Mentors, scientific advisors, 
the project coordinator, and 
Safety Officer 
Status of enrolled subjects as of date of 
reporting 
Quarterly 
Co-Mentors, scientific advisors, 
the senior RA, and Safety Officer 
Adherence data regarding study visits and 
intervention 
Quarterly 
Co-Mentors, scientific advisors, 
the senior RA, and Safety Officer 
AEs and rates 
Quarterly 
Co-Mentors, scientific advisors, 
the senior RA, and Safety Officer 
  
Safety Review Plan. Study progress and safety will be reviewed monthly. The PI will provide 
progress reports, including patient recruitment, attrition, and AEs to the Co-Mentors, scientific 
advisors, the senior RA, and Safety Officer following each of the monthly reviews. An Annual 
Report will be compiled including 1) a list and summary of AEs; 2) whether AE rates are 
consistent with pre-study assumptions; (3) reason for dropouts from the study; (4) whether all 
participants met enrollment criteria; (5) whether continuation of the study is justified on the basis 
that additional data are needed to accomplish the stated aims of the study; and (6) conditions 
whereby the study might be terminated prematurely. The Annual Report will be sent to the Co-
Mentors, scientific advisors, the senior RA, and Safety Officer and forwarded to the IRB and 
NIH/NIMHD. The IRB will review progress of this study on an annual basis. The PI will also send 
copies of signed recommendations and comments from the Safety Officer to the NIMHD 
Program Officer within 1 month of each monitoring review. 
  
Interim Analysis. The senior RA 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. 

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The 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. Stopping Rules. There 
are no planned stopping rules for this study. Protocol Modifications. Modifications will not be 
undertaken without notification of the IRB, Safety Officer, and NIMHD Program Officer.  
8.3.5 ADVERSE EVENT REPORTING 
  
See 8.3.1, 8.3.3.2, and 8.3.4 above 
8.3.6 SERIOUS ADVERSE EVENT REPORTING 
  
See 8.3.1, 8.3.3.2, and 8.3.4 above 
8.3.7 REPORTING EVENTS TO PARTICIPANTS 
  
See 8.3.1, 8.3.3.2, and 8.3.4 above 
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 health care provider. 
8.4 UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
  
See 8.3.1, 8.3.3.2, and 8.3.4 above. 
8.4.2 UNANTICIPATED PROBLEMS REPORTING 
  
See 8.3.1, 8.3.3.2, and 8.3.4 above. 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS 
  
N/A 
 
 

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9 STATISTICAL CONSIDERATIONS 
9.1 STATISTICAL HYPOTHESES 
Aim 1: To examine the feasibility of the multi-component behavioral intervention. We will 
assess enrollment and retention rates; barriers and facilitators to enrollment; intervention fidelity; 
suitability of study procedures and outcome measures; and participant satisfaction with the 
intervention and study protocol. 
  
Aim 2: To evaluate the initial efficacy of the intervention by comparing an intervention 
group to a wait-list control group (n=80; 40 per group) in a pilot study to a) decrease the 
primary outcomes of biologic CVD risk factors (blood pressure [BP], arterial stiffness, lipids, 
blood glucose); b) improve secondary outcomes (health behaviors: nutrition, physical activity, 
sleep, coping strategies) and other biological factors related to CVD risk (adiposity, 
inflammatory and stress biomarkers, vasomotor symptoms) from Time 1 (baseline) to Time 2 (6 
months) and Time 3 (12 months). 
  
Hypotheses and Statistical Considerations: This pilot study will descriptively assess the 
feasibility and validity of the cluster randomized controlled trial plan and is not expected to 
test the hypotheses of the main clinical trial.  
  
We expect that on average, the intervention group will have a slower progression or a decrease 
in BP, arterial stiffness, lipids, and blood glucose compared to the wait-list control from Time 1 
(baseline) to Time 2 (6 months) and Time 3 (12 months). 
  
We expect the intervention group will show improvements in health behaviors (nutrition, physical 
activity, sleep, coping strategies, self0efficacy), adiposity, inflammatory and stress biomarkers, 
and vasomotor symptoms from Time 1 (baseline) to Time 2 (6 months) and Time 3 (12 months). 
9.2 SAMPLE SIZE DETERMINATION 
Sample size will be limited by available resources. Prior clinical trials among Latinas in North 
Carolina have enrolled 80-184 women successfully with <20% attrition [45]; therefore, 
enrollment of 80 women is realistic and achievable. Prior interventions in stress 
management [46] and exercise plus nutrition education [47] observed a change in systolic BP of 
6mmHg (SD±11); our sample of 80 participants will yield 70% power to detect a change this 
large. This pilot study is effectively a cluster-randomized trial with two groups. Because we have 
two groups, the pilot is not sufficient for the estimation of intraclass correlation of change in 
outcomes, so we do not use traditional analysis methods for cluster-randomized trials. We can 
however, use baseline data to estimate potential variability between clusters, which will be 
helpful in the estimation of the number of clusters/cluster size required for the fully-powered 
clinical trial. 
 

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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 age, education, income, or other 
participant characteristics. 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 
  
Aim 1. Using descriptive statistics (e.g., frequency, percentage, means, SDs), we will 
summarize enrollment and retention rates, and proportion of intervention sessions the 
participants attended. We will measure fidelity of the intervention (³80% attendance; delivery of 
>80% of content) using the process evaluation guide, and assess participant satisfaction with 
the study and the intervention using the exit interview. 
  
Aim 2. We will use an intent-to-treat approach. Because random assignment is by group and not 
individually, we will examine potential systematic differences closely between the two groups, 
comparing baseline characteristics using the Student’s t-test or Mann-Whitney test for 
continuous variables and Chi-square or Fisher’s exact test for categorical variables. We will 
assess change in primary and secondary outcomes in the intervention and control group using 
using the Student’s t-test or Mann-Whitney test for continuous variables and Chi-square or 
Fisher’s exact test for categorical variables.  
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
  
See 9.4.1 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
  
See 9.4.1 
9.4.4 SAFETY ANALYSES 
  
N/A 

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9.4.5 BASELINE DESCRIPTIVE STATISTICS 
  
The outcomes of most feasibility and pilot studies are measured with descriptive statistics, 
qualitative analysis, and the compilation of basic data related to administrative and physical 
infrastructure. At baseline we will determine means, standard deviations, minimums, medians, 
and maximums for each continuous variable; frequencies and percentages will be tabulated for 
each categorical variable. 
9.4.6 PLANNED INTERIM ANALYSES 
  
As discussed in 9.4.1., we will analyze the effect of the intervention on change biologic CVD risk 
factors (i.e., blood pressure, weight, was it circumference, BMI), and health behaviors from 
baseline to Time 2 (6 months [completion of the intervention]). 
9.4.7 SUB-GROUP ANALYSES 
  
See 9.4.1 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
  
See 9.4.1 
9.4.9 EXPLORATORY ANALYSES 
  
See 9.4.1 
 
 

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
  
See human subjects section above for details of consent. 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS 
PROVIDED TO PARTICIPANTS 
  
See human subjects section above for details of consent. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
  
See human subjects section above for details of consent. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
  
At the completion of four years or 48 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. 

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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 
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. We will not store any biological specimens. 

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10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator  
Medical Monitor or Independent 
Safety Monitor 
Dr. Yamnia I. Cortés 
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 
919-966-5299 
919-966-5450 
yicortes@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, blood pressure, and collection of arterial stiffness measurements and questionnaire and 
accelerometer data. 
  
Quality control (QC) procedures will be implemented as follows: 
  
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. 

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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 
  
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. 

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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 NIMHD 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 
ANCOVA Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 

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DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
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 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator's Brochure 
ICH 
International Council on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
LSMEANS Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
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 
SOC 
System Organ Class 
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 
 2.0 
 6-20-20 
Procedures may be conducted 
virtually. In-person visits for data 
collection should be performed 
with proper facial covering and 
sanitizing. Prior to scheduling 
visits, research assistants must 
ask about COVID-19 symptoms 
and exposures (see attachment). 
During screening, participants will 
receive information about 
participating in a research study 
during COVID-19. 
   
5.5., 6.0, 8.0 
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protect staff and participants 
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Reducing Cardiovascular Risk in Perimenopaual Latinas: Pilot Study of a Multi-Component 
Intervention 
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Protocol  
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