Pilot Study to Evaluate the Feasibility of Using a Sequential Multiple Assignment Randomized Trial to Address Food Insecurity in Patients With Hypertension (Pilot SMART-FI)
Phase: NA
Conditions: Hypertension
Sponsor: Wake Forest University Health Sciences

Protocol version: 1 
 
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Study Title: Pilot study to evaluate the feasibility of using a Sequential Multiple Assignment 
Randomized Trial to Address Food Insecurity in patients with Hypertension (Pilot SMART-FI) 
 
 
 
Principal Investigator, Co-investigator(s): 
Deepak Palakshappa (PI) 
 
Sponsor or funding source: NIH 
 
Document date: May 5, 2023 
 
Document modified date: May 8, 2023 
 
Wake Forest University School of Medicine IRB approval date: May 8, 2023 
 

Protocol version: 1 
 
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Background, Rationale and Context 
In the US, 47% of adults have hypertension (HTN), and HTN accounts for more cardiovascular disease 
(CVD) deaths than any other CVD risk factor.1,2 Despite advances in prevention and treatment, barriers to 
adherence are common and HTN disparities remain pervasive. Populations that have been socially and 
economically disadvantaged have a greater prevalence of HTN, worse blood pressure control, and are at 
higher risk of developing CVD from HTN.3-6 Food insecurity (FI), the lack of consistent access to 
nutritionally adequate foods, is an important social need that affects 30 million people in the US, impacts 
adherence to treatment, and contributes to HTN disparities.7,8 Increasingly, health systems are investing in 
interventions to address FI as part of routine care, including lower-cost, low intensity (e.g. providing 
information about community resources) and higher-cost, high intensity (e.g. using community health 
workers (CHWs), delivery of medical tailored meals (MTM)) interventions.9-12 However, individuals 
often need varying levels of support to address social needs, and, rather than dispensing a fixed 
intervention, adaptively allocating treatment resources has the potential to more effectively and efficiently 
improve food security and blood pressure for a greater proportion of patients. Thus, the lack of an 
adaptive, stepped-care intervention to address FI in patients with HTN is a critical problem affecting a 
large, vulnerable population. 
 
Objectives 
The objective of this study is to conduct a pilot sequential multiple assignment randomized trial 
(SMART) addressing food insecurity in patients with uncontrolled HTN to determine the feasibility of 
recruitment/retention and the potential impact on blood pressure in anticipation of a larger more definitive 
trial. 
 
Methods and Measures 
 
Design 
We will conduct a longitudinal two-stage, single-site pilot SMART to determine the feasibility and 
potential impact of the embedded adaptive interventions to improve systolic blood pressure (SBP) among 
food insecure patients with uncontrolled HTN (see Figure below).13,14 Patients from 1 clinic within 
AHWFB with uncontrolled HTN (BP >130/80) who screen positive FI will be eligible for inclusion. We 
will follow participants for a total of 6 months. We will randomize eligible consenting participants to one 
of two first-stage interventions: 1) information about local community resources or 2) assistance from a 
community health worker (CHW). We will assess all participants at 3 months. All participants who do not 
have a reduction of at least 10mmHg in SBP (suboptimal respondents) will be re-randomized, with equal 
probability, to receive one of two second-stage interventions: 1) initial or continued assistance with a 
CHW or 2) weekly medically tailored meals (MTM.) We will assess the feasibility of recruitment 
(percent of patients who were eligible and who consented) and retention (percent of patients who were 
enrolled who completed follow up data collection).  
 
Setting 
The study will take place in the General Medicine Clinic at Janeway Tower (OPD) 
 
 
Subjects selection criteria 
 
Inclusion Criteria 
Adult patients (≥18 years of age) will be included if (1) have a diagnosis of HTN (defined by ICD-10 
code) or have been prescribed at least one blood pressure medication (including thiazide diuretic, calcium 
channel blocker, beta-blocker, angiotensin-converting enzyme inhibitors, or angiotensin receptor 
blocker); (2) blood pressures at their primary care office was >130/80; (3) experience FI based on the 2-
item Hunger Vital Sign; and (5) live in Winston-Salem or Forsyth County.  

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Exclusion Criteria 
Participants will be excluded if they are (1) unable to speak English or Spanish; (2) have severe cognitive 
impairment or major psychiatric illness that prevents consent and participation; (3) lack of safe, stable 
residence and ability to store meals; (4) pregnant, breastfeeding, or planning to become pregnant in the 
next year; (5) advance kidney disease (estimated creatine clearance < 30 mL/min); (6) serious medical 
condition which either limits life expectancy or requires active management (e.g. certain cancers); (7) 
those planning on moving out of the geographic area within 12 months; (8) lack of a telephone (>80% of 
patients list a cell phone number in the EHR). 
 
Sample Size 
The goal of this study is to determine the feasibility of testing the SMART design, recruitment and 
retention, data collection, and to provide information to refine the study protocol for a larger study 
powered to determine differences in the future. Our goal is to recruit 60 participants. A sample size of 60 
participants will provide a >90% chance of having at 4 participants in each subgroup assuming 20% 
attrition (12 people lost to follow up).  
 
Interventions and Interactions 
First-stage treatment options: 
1. Resource information: Participants randomized to the resource referral arm will receive a tailored list of 
information about community resources. The list will include information about local emergency food 
resources (e.g. local food pantries) and government programs to address FI (e.g. SNAP).  
 
2. CHW assistance: The CHW will assist participants in addressing FI and supporting them in their blood 
pressure management. Participants randomized to the CHW intervention will have an initial baseline visit 
scheduled at a mutually convenient location. The purpose of the baseline visit is to build rapport and trust 
with the patient and being able to identify and address social and structural factors that affect the 
participant’s health and healthcare. Follow-up visits will occur at home, over the telephone, and in-person 
at participant’s regularly scheduled patient visits based on the needs of the participant. During the follow-
up visits, the CHW will monitor the participants’ progress with care plans, elicit and address additional 
barriers, reinforce health education, and facilitate patient and family empowerment.  
 
Tailoring variable: We will assess all participants at 3 months. Participants who do not have at least a 
10mmHg decrease in SBP at 3 months (suboptimal respondents) will be re-randomized to one of two 
second-stage interventions.  
   
Second-stage treatment options: 
1. CHW assistance: The CHWs will provide the same assistance as described above. Participants 
randomized to resource information in the first-stage and will be new to receiving CHW assistance, will 
have an initial baseline visit scheduled to build rapport and trust with the patient. Participants who had 
been randomized to the CHWs in the first-stage intervention will continue to work with the same CHW 
for an additional 3 months. We are including an additional 3 months of working with a CHW as a 
treatment option for participants because the optimal time individuals need to work with a CHW is 
unclear.  
 
2. MTM:  The MTM will consist of weekly home meal delivery and will be provided by Providence 
Community Kitchen, which is a program of Second Harvest Food Bank of Northwest NC. During the 3 
months of meal provisions, participants will receive 10 medically tailored refrigerated or frozen meals (5 
lunches and 5 dinners) delivered to the participant’s home weekly. Meals are refrigerated or frozen, have 
minimal preparation time, and can be heated by stove, oven, or microwave.  
 

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Outcome Measure(s) 
The goal of this aim is to determine the feasibility of testing the SMART design, recruitment and 
retention of participants, data collection, and to provide information to refine the future study protocol. 
We will assess blood pressure (using ambulatory blood pressure cuffs) and surveys at baseline, 3 months, 
and 6 months. Additionally, we will extract demographic data from the electronic health record including 
age, sex, race/ethnicity, health insurance, medications, neighborhood socioeconomic characteristics, and 
Charlson Comoribidity Index. We are collecting insurance to see if response varies by insurance coverage 
as many private and public insurers are considering including food insecurity interventions as part of their 
benefits coverage. We will also collected data on which services were provided from the CHW through 
data extraction from the EHR.  
 
Analytical Plan 
Results will be analyzed initially using descriptive statistics.  Comparison between groups will be done 
using chi square tests for proportions, and t-tests or ANOVA procedures for continuous variables.  
Regression analysis will be performed to identify independent outcome predictors.  Other inferential 
statistical analysis will be conducted as appropriate. We will use descriptive statistics to summarize the 
feasibility of recruitment and retention. We will used repeated measure ANOVA to evaluate change in 
blood pressure over time to estimate measures of variance to assist in sample size calculations for a future 
large randomized trial. 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
We will identify patients living with HTN whose blood pressure at their last primary care visit was 
>130/80 through review of the clinic schedule and EHR.  Patients that could be eligible will be contacted 
by phone prior to their scheduled visit to briefly discuss the study goals and gauge interest in 
participating. We are requesting a limited waiver of HIPAA authorization as potential subjects will be 
assessed prior to interacting with the study. We will collect he potential subject’s name, telephone 
number, age (in years), problem list (to see if they have a diagnosis of hypertension), and most recent 
blood pressure to determine if they meet eligibility requirements. Confidentiality and privacy will be 
protected by collecting only information needed to assess study eligibility, stored on a secure password 
protected data file, and data access will be limited to study staff only. For potential participants that 
decline, name, telephone number, and problem list will be immediately destroyed. Age and reason for 
declining (if provided) will be destroyed 3 years after study completion. 
 
For those interested, we will approach eligible participants in the clinic after their routine visit with the 
clinician. All potential patients will be assessed using the screening questionnaire. We will further discuss 
with eligible, interested participants the study goals, objectives, and procedures and obtained informed 
consent. After consent is obtained, we will collect baseline data and teach participants how to properly 
use the ambulatory blood pressure monitors. After baseline data collection is obtained, participants will be 
randomized to one of the two first-stage interventions. 
 
 
Informed Consent 
Signed informed consent will be obtained from each subject who is recruited in person. A study team 
member (e.g. PI, co-investigators, study coordinator, or other study team member) will obtained informed 
consent. A study team member will obtain consent in a quiet area within the primary care clinic.    
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 

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subjects, and maintaining all study information in a secure manner.  To help ensure subject privacy and 
confidentiality, only a unique study identifier will appear on the data collection form.  Any collected 
patient identifying information corresponding to the unique study identifier will be maintained on a 
linkage file, store separately from the data.  The linkage file will be kept secure, with access limited to 
designated study personnel.  Following data collection subject identifying information will be destroyed 
three years after closure of the study consistent with data validation and study design, producing an 
anonymous analytical data set.  Data access will be limited to study staff.  Data and records will be kept 
locked and secured, with any computer data password protected.  No reference to any individual 
participant will appear in reports, presentations, or publications that may arise from the study. 
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will 
be promptly reported by the principal investigator or designated member of the research team to the IRB 
and sponsor or appropriate government agency if appropriate. 
 
 

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Figure: SMART-FI Pilot Design  
 
 
 
 
 
Appendix 
1. Screening questionnaire 
2. Baseline questionnaire 
3. Follow up questionnaires 
4. Data collection form 
5. Consent form  
 
 
 
 
 
 
 
 
 
 
 
 
 

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References: 
 
1. 
Carey RM, Moran AE, Whelton PK. Treatment of Hypertension: A Review. JAMA : the 
journal of the American Medical Association. 2022;328(18):1849-1861. 
2. 
Services USDoHaH. The Surgeon General’s Call to Action to Control Hypertension. In: 
Department of Health and Human Services OoSG, ed. Washington, DC2020. 
3. 
Mahdavi R, Bagheri Asl A, Abadi MAJ, Namazi N. Perceived Barriers to Following 
Dietary Recommendations in Hypertensive Patients. J Am Coll Nutr. 2017;36(3):193-
199. 
4. 
Soltani S, Arablou T, Jayedi A, Salehi-Abargouei A. Adherence to the dietary approaches 
to stop hypertension (DASH) diet in relation to all-cause and cause-specific mortality: a 
systematic review and dose-response meta-analysis of prospective cohort studies. Nutr J. 
2020;19(1):37. 
5. 
Epstein DE, Sherwood A, Smith PJ, et al. Determinants and consequences of adherence 
to the dietary approaches to stop hypertension diet in African-American and white adults 
with high blood pressure: results from the ENCORE trial. Journal of the Academy of 
Nutrition and Dietetics. 2012;112(11):1763-1773. 
6. 
Choudhry NK, Kronish IM, Vongpatanasin W, et al. Medication Adherence and Blood 
Pressure Control: A Scientific Statement From the American Heart Association. 
Hypertension. 2022;79(1):e1-e14. 
7. 
Coleman-Jensen A, Rabbitt MP, Gregory CA, Singh A. Household Food Security in the 
United States in 2020, ERR-298. In: U.S. Department of Agriculture ERS, ed2021. 
8. 
Gregory C, Coleman-Jensen A. Food Insecurity, Chronic Disease, and Health Among 
Working-Age Adults, ERR-235. In: Agriculture USDo, ed. Economic Research 
Service2017. 
9. 
De Marchis EH, Torres JM, Benesch T, et al. Interventions Addressing Food Insecurity 
in Health Care Settings: A Systematic Review. Annals of family medicine. 
2019;17(5):436-447. 
10. 
De Marchis EH, Torres JM, Fichtenberg C, Gottlieb LM. Identifying Food Insecurity in 
Health Care Settings: A Systematic Scoping Review of the Evidence. Family & 
community health. 2019;42(1):20-29. 
11. 
De Marchis EH, Hessler D, Fichtenberg C, et al. Part I: A Quantitative Study of Social 
Risk Screening Acceptability in Patients and Caregivers. American journal of preventive 
medicine. 2019;57(6S1):S25-S37. 
12. 
Byhoff E, De Marchis EH, Hessler D, et al. Part II: A Qualitative Study of Social Risk 
Screening Acceptability in Patients and Caregivers. American journal of preventive 
medicine. 2019;57(6S1):S38-S46. 
13. 
Kidwell KM, Almirall D. Sequential, Multiple Assignment, Randomized Trial Designs. 
JAMA : the journal of the American Medical Association. 2023;329(4):336-337. 
14. 
Bigirumurame T, Uwimpuhwe G, Wason J. Sequential multiple assignment randomized 
trial studies should report all key components: a systematic review. Journal of clinical 
epidemiology. 2022;142:152-160.