Team Science to Identify & Intervene on Metabolism- & Alcohol-Associated Liver Disease
Phase: NA
Conditions: Steatotic Liver Disease of Mixed Origin (MetALD)
Sponsor: Brown University

 
Page 1 of 21 
 
 
PROTOCOL TITLE: TEAM SCIENCE TO IDENTIFY AND INTERVENE ON 
METABOLISM- AND ALCOHOL-ASSOCIATED LIVER DISEASE (METALD) 
 
PROTOCOL TITLE: 
Team Science to Identify and Intervene on Metabolism- and Alcohol-Associated Liver 
Disease (MetALD) 
 
PRINCIPAL INVESTIGATOR: 
Hayley Treloar Padovano, PhD 
Center for Alcohol & Addiction Studies 
Center for Addiction & Disease Risk Exacerbation  
(401) 863-6623 
hayley_treloar@brown.edu 
VERSION NUMBER/DATE: 
Version 1, September 30, 2024 
 
 
 

 
Page 2 of 21 
 
 
Table of Contents 
1.0 
3 
2.0 
4 
3.0 
Error! Bookmark not defined. 
4.0 
5 
5.0 
6 
6.0 
7 
7.0 
10 
8.0 
10 
9.0 
11 
10.0 11 
11.0 12 
12.0 12 
13.0 12 
14.0 14 
15.0 15 
16.0 15 
17.0 15 
18.0 17 
19.0 17 
20.0 17 
21.0 17 
22.0 17 
23.0 18 
24.0 18 
25.0 19 
26.0 Error! Bookmark not defined. 
 
 
 

 
Page 3 of 21 
 
 
1.0 
Study Summary 
 
Protocol Information  
Description  
Study Title 
Team Science to Identify and Intervene on Metabolism- and 
Alcohol-Associated Liver Disease (MetALD) 
Study Design 
The research design is a mixed-methods randomized 
controlled trial (RCT) comparing standard and enhanced 
approaches to screening, brief intervention, and referral to 
treatment (SBIRT/P) for metabolism- and alcohol-associated 
liver disease (MetALD). Adults age 21+ with indicated risks 
for MetALD based on alcohol intake and body mass index 
(BMI) and who speak Spanish or English are offered free, 
confidential liver screening with Fibroscan®, a noninvasive, 
painless ultrasound to measure stiffness and fat in the liver. 
Procedures include a prescreening survey, in-person 
screening, a randomization visit, and a ~30-day followup 
visit. At the end of the randomization visit, participants 
receive a brief intervention to increase motivation for healthy 
lifestyle which includes either integrated Fibroscan® results 
or standard health information. At the end of the followup 
visit, participants complete exit interviews to obtain 
qualitative data to supplement quantitative indices of 
feasibility, acceptability, and small-scale effectiveness. 
Primary Objective 
The primary aim of the research is to show that SBIRT/P 
can be optimized by integrating results of noninvasive 
Fibroscan® liver screening for adults age 21+ from 
underresourced communities and with behavioral risks for 
MetALD. 
Secondary 
Objective(s) 
Secondary aims are to evaluate the precision of 
biobehavioral endpoints for alcohol intake, weight-related 
behaviors, and cardiometabolic health, and to explore 
plasma biomarkers to indicate likely steatosis and fibrosis, 
with Fibroscan® as a reference standard. 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
All participants receive SBIRT/P including a brief 
intervention to increase motivation for healthy lifestyle, 
toward the end goal of reducing risk of multiple chronic 
conditions, including MetALD. In the standard SBIRT/P 
condition, the brief intervention includes standard health 
information. In the enhanced SBIRT/P condition, results of 
noninvasive Fibroscan® liver screening and staging are 
integrated to optimize intervention benefit. 
IND/IDE #  
NA 
Study Population 
Adults 21 years of age or older with concurrent risk factors 
for MetALD based on alcohol intake and body mass index 
and who speak Spanish or English. 
Sample Size 
The target number of participants to be randomized is 40 
(20 per condition). An estimated 80 potential participants will 
complete informed consent prior to in-person screening to 
confirm eligibility, allowing for screen failures and disinterest. 

 
Page 4 of 21 
 
 
Study Duration for 
individual 
participants 
Eligible participants are scheduled for a randomization visit, 
typically within 5 to 10 business days of in-person screening. 
Approximately 30 days after the randomization visit, 
participants return for a followup visit to repeat measures 
and assess satisfaction with SBIRT/P. The total study 
duration is typically 45 days or less, with flexibility to 
accommodate schedules. 
Study Specific 
Abbreviations/ 
Definitions  
Alcohol-associated liver disease (ALD) 
Alcohol use disorder (AUD) 
Body mass index (BMI) 
Metabolic dysfunction-associated steatotic liver disease 
(MASLD) 
Metabolism- and alcohol-associated liver disease (MetALD) 
Motivational Interviewing Treatment Integrity (MITI) 
Randomized controlled trial (RCT) 
Screening, brief intervention, and referral to treatment 
(SBIRT/P) 
Vibration controlled transient elastography (VCTE) 
 
 
 

 
Page 5 of 21 
 
 
2.0 
Objectives 
2.1 
The purpose of this randomized controlled trial (RCT) is to test whether 
screening, brief intervention, and referral to treatment and prevention 
(SBIRT/P) is improved by integrating results of noninvasive liver imaging 
with Fibroscan® for adults age 21+ from underresourced communities who 
speak English or Spanish and are at risk for metabolism- and alcohol-
associated liver disease (MetALD). 
2.2 This research aims to demonstrate that SBIRT/P is an effective way to 
identify and intervene for MetALD in underresourced communities. 
Identifying individuals with alcohol intake and overweight-related risks for 
MetALD and engaging them in brief intervention to promote healthy lifestyle 
can reduce risk of multiple chronic diseases, including MetALD. We 
hypothesize that integrating results of noninvasive liver screening and 
staging with Fibroscan® liver imaging will enhance the effectiveness of a 
brief intervention to promote liver and heart health, as compared to a brief 
intervention with standard health information. 
3.0 
Background 
3.1 
Chronic, steatotic liver disease is a leading cause of death in the United States 
(US) and worldwide. As alcohol intake and obesity rates remain high and rising, 
and the population of adults in the US who are at risk for irreversible liver damage 
and cardiometabolic health problems is substantial, particularly among 
underresourced communities. Updated nomenclature and criteria provide a 
standardized, inclusive, and nonstigmatizing framework to identify adults at risk for 
or with steatotic liver disease. In addition to metabolic dysfunction-associated 
steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), a 
concurrent-etiology type, metabolism and alcohol-associated liver disease 
(MetALD), identifies those whose drinking may not have yet progressed to the 
levels seen for patients with ALD but who have an additional cardiometabolic risk 
factor for chronic steatotic liver disease.  
3.2 Observational data show that obesity worsens ALD severity, and any 
drinking accelerates MASLD. Yet, there is currently no preventative 
interventions or medical treatments to simultaneously address weight-
related behaviors and alcohol use to decrease risk for progressive liver 
damage from both etiologies in MetALD. Importantly, liver disease from 
alcohol intake and metabolic etiologies is preventable and treatable only 
through lifestyle changes. Our preliminary data from patients with alcohol 
use disorder (AUD) and at-risk for or with ALD demonstrated feasibility and 
acceptability of a brief motivational intervention to reduce alcohol 
consumption, delivered in English and Spanish for adults recruited from 
specialty liver clinics and remotely from the community.  
3.3 Whereas liver-related deaths due to viral infection have declined sharply in 
recent years through groundbreaking treatments, mortality rates for liver 
diseases related to alcohol intake and obesity have risen. If left 
unaddressed, MetALD mortality rates are projected to double by 2040. 
Research to develop effective strategies to identify and intervene for 
MetALD in underresourced communities is essential and has potential to 
help many people avoid irreversible liver damage. Screening, brief 

 
Page 6 of 21 
 
 
intervention, and referral to treatment/prevention (SBIRT/P) is an effective 
way to promote liver health and avoid irreversible damage. Interventions to 
reduce alcohol intake and weight-related behaviors, such as high-fat diet 
and sedentary lifestyle, are efficacious when delivered, but as many as 
90% of those who need intervention are not being reached. In Latinx 
communities, lack of societal privilege and language barriers can intensify 
disparities in access to alcohol services, weight management, and linkage 
to liver care, with deadly and costly outcomes. SBIRT/P integrated at the 
point of care is a promising strategy to reach people at risk for MetALD, 
avoid progressive liver damage, and address socioeconomic barriers in 
communities experiencing health disparities. 
4.0 
Study Endpoints 
4.1 Primary endpoints include: (a) proportion screened who have alcohol intake 
and weight-related risks for MetALD; (b) proportion eligible and invited to 
participate who agree to noninvasive liver imaging with Fibroscan® and 
arrive for their scheduled appointment; (c) satisfaction with Fibroscan® liver 
screening; and (d) acceptability metrics for SBIRT/P overall, including 
retention rates and satisfaction ratings compared across randomized 
conditions. Satisfaction with Fibroscan liver screening is assessed with a 
single-item visual analog scale with 0 indicating low satisfaction and 100 
indicating high satisfaction. Satisfaction with SBIRT/P overall is assessed 
with the Client Satisfaction Questionnaire, provided in an attachment. 
4.2 Secondary endpoints include: (a) self-reported drinking quantity and 
frequency (e.g., heavy drinking days, drinks per week, alcohol-free days); 
(b) phosphatidylethanol (PEth), a direct alcohol metabolite biomarker; (c) 
self-reported weight-related behaviors (e.g., diet quality, eating 
dysregulation, food cravings, and physical activity); and (d) weight-related 
biometrics (e.g., body weight, waist circumference, blood pressure). 
Descriptions and items for secondary-endpoint measures are provided in 
an attachment. Measures to describe the sample participating in this 
research, to account for important covariates, and to facilitate team science 
are also attached. The battery of measures is streamlined from prior 
projects to reduce staff time, minimize participant burden, and facilitate 
remote data collection. 
4.3 Exploratory endpoints include plasma biomarkers to comprise a preliminary 
panel to screen for likely steatosis and fibrosis in patients at risk for 
MetALD, with Fibroscan® as a reference standard. These include plasma 
biomarkers of microbial translocation, innate immune activation, obesity-
related metabolic dysfunction, and liver fibrosis. 
5.0 
Study Intervention/Investigational Agent 
5.1 In the standard SBIRT/P condition: Information about the participant’s 
alcohol- and weight-related risk factors for MetALD is provided. The 
information includes comparison of the participant’s health metrics with 
public-health guidelines. 
5.2 In the enhanced SBIRT/P condition: Results of noninvasive liver imaging 
and staging via Fibroscan® is integrated into the brief behavioral 
intervention to enhance motivation for healthy lifestyle behaviors, reduce 

 
Page 7 of 21 
 
 
risk of multiple chronic diseases including MetALD, and promote overall 
health and wellness. The information includes interpretation of the 
participant’s Fibroscan® steatosis and liver stiffness measurements based 
on MetALD diagnostic criteria and published liver-health guidelines. 
5.3 Randomized conditions include either standard or enhanced health 
information in the setting of evidence-based, motivational interviewing (MI). 
A treatment manual has been cultivated over decades of research by this 
team and multiple prior clinical research protocols including our recent 
study of brief MI for AUD and ALD. The intervention has the potential to 
have high impact on the dual etiologies of MetALD, i.e., alcohol 
consumption and weight-related behaviors. 
5.4 N/A. IND/IDE are not applicable. The Fibroscan® is a well-established 
research and clinical screening tool for steatosis and fibrosis. Fibroscan® is 
the gold standard procedure for obtaining information on liver health and is 
the primary noninvasive diagnostic screening method used in research and 
clinical practice prior to an invasive liver biopsy. 
5.5 Fidelity (adherence) monitoring via Motivational Interviewing Treatment 
Integrity coding system (MITI Coding Manual 4.1; Moyers, Manual, & Ernst, 
2014) will evaluate the degree to which the intervention is delivered by the 
interventionist(s) as intended with consistency across randomized groups 
and facilitate supervision of the intervention by a licensed clinical 
psychologist or other licensed practitioner in Rhode Island.  
6.0 
Procedures Involved 
6.1 Study procedures described herein do not involve more than minimal risk. 
The research design is a mixed-methods RCT comparing standard and 
enhanced approaches to SBIRT/P for MetALD. The research, including all 
procedures and materials, is implemented in English and Spanish. Any 
modifications of study procedures described herein will be reviewed and 
approved by the Brown University IRB. The addition of key personnel will 
be submitted to the IRB and appended to the IRB record upon 
administrative review. All personnel will have documented human subjects 
research training prior to engaging in research activities.  
6.2 This study builds upon prior research through partnering with Clínica 
Esperanza/Hope Clinic (CEHC) to address issues of low and inequitable 
access to alcohol health services and liver specialty services across the 
care continuum. CEHC is the primary site for recruitment and data 
collection, and established partnerships with Brown Medicine primary care 
clinics can supplement to meet enrollment targets. The section on 
recruitment methods provides information to describe recruitment 
procedures and participant compensation.  
6.3 Interested volunteers complete a brief, confidential pre-screening survey to 
assess eligibility and provide basic demographic information to describe the 
sample of potential participants reached for screening by these procedures. 
The pre-screening survey questions to assess eligibility and an 
accompanying script are provided in an attachment. Responses to the pre-
screening survey are recorded via Brown-approved, HIPAA-compliant 
survey software for the purpose of tracking reasons for ineligibility. 

 
Page 8 of 21 
 
 
Personally identifiable contact information will be securely stored using 
HIPAA-compliant software vetted and approved by Brown CIS. After pre-
screening in partnering clinics or over the phone, a community health 
worker (e.g., patient navigator or Navegante) or Brown University staff 
member approaches the potential participant in the clinic or schedules them 
for an appointment where procedures and risks are explained in person and 
supplemented by a bulleted written consent form. The consent section of 
this protocol describes informed consent procedures, which are always 
done in person via an interactive conversation and documented in writing. 
Interested volunteers who would like to participate in screening, appear 
potentially eligible, and complete informed consent with written 
documentation continue with screening that day, or, if necessary, are 
scheduled for a visit as soon as possible. Eligibility criteria assessed 
include interviews, weight-related biometrics, and blood tests, including 
tests for Hepatitis B and C which are common exclusionary preexisting liver 
diseases in this population. Additional measures include culturally validated 
assessments of diet and lifestyle behaviors, described in attachments. 
6.4 Those eligible are scheduled for two appointments: (1) a randomization visit 
typically completed within 5 to 10 business days of in-person screening, 
and (2) a followup visit ~30 days later. Attendance at all visits is facilitated 
by reminders in multimethod formats, including email, text message, phone 
call, and/or calendar invitations, complying with the participant’s 
preferences. The first visit includes the Fibroscan® liver screening, 
biobehavioral assessments, interviews, and a brief conversation with our 
study counselor (~45 minutes to 1 hour) to build motivation for lifestyle 
change. The followup visit repeats biobehavioral assessments and 
interviews and includes a brief check-in (~15 minutes) with our study 
counselor with an exit interview assessing satisfaction with study 
procedures and barriers to change. The Fibroscan® liver screening is not 
repeated at followup. For participants who are monolingual Spanish 
speakers or bilingual and prefer to complete the study in Spanish, all 
procedures including the brief intervention will be implemented in Spanish 
by bilingual personnel who are either native Spanish speakers or have 
documented professional Spanish fluency. The total study duration for 
individual participants is typically less than 45 days, with some variability to 
allow for flexibility in scheduling.  
6.5 Plain language is used to describe what will happen during the Fibroscan® 
and the procedures for sharing results. During informed consent, visual aids 
are used to facilitate patients’ understanding of the procedures, and a 
specific pause point is written into the bulleted consent form to solicit 
questions. Participants are informed that they may or may not receive their 
liver scan results from their study counselor and that this is decided 
randomly, like a coin flip. In the enhanced condition, our study counselor 
receives the Fibroscan® results and shares these with the participant in the 
context of the brief motivational interviewing intervention. In the standard 
condition, the same brief motivational interviewing intervention is 
implemented but includes standard information on lifestyle behaviors and 
risks without the specific results of the Fibroscan® examination. In both 
conditions, the Fibroscan® results are reviewed by our study physician, 
Kittichai Promrat, MD, who is a Brown-affiliated faculty member and 

 
Page 9 of 21 
 
 
experienced hepatologist directing the Chapman Street Hepatology Clinic 
and is chief of gastroenterology at the Providence VAMC. Fibroscan® 
results can be reviewed remotely via encrypted, HIPAA-compliant 
communication and software provided by the manufacturer, Echosens, 
https://www.echosens.com/en-us/. Referrals to primary or specialty care for 
an evaluation will be facilitated by Dr. Promrat, as appropriate, consistent 
with best-practice clinical guidelines. There is also an independent medical 
monitor for this study, Lorenzo Leggio, MD, PhD, an addiction-scientist and 
hepatologist with extensive experience in this role. Dr. Leggio will review 
individual serious adverse events as well as cumulative progress reports 
and make recommendations regarding safety and continuation of the study. 
6.6 Sources of research data include (a) self-reported data collected by trained 
staff via interviews and questionnaires, (b) self-reported data collected via 
HIPAA-compliant survey tools that have been vetted and approved by 
Brown CIS, stored on HIPAA-compliant, cloud-based servers, and 
monitored by staff with up-to-date human subjects training, (c) biological 
specimens collected, stored, and transported by trained staff, and 
processed in our Clinical Laboratory Core (CLC) laboratory at Brown 
University or at HIPAA-compliant clinical laboratories (d) biometrics (e.g., 
height, weight, blood pressure, waist circumference) collected by research 
staff using structured protocols, and (e) transient elastography Fibroscan® 
to obtain Controlled Attenuation Parameter (CAP)TM score and Liver 
Stiffness Measurement (LSM) by Vibration Controlled Transient 
Elastography (VCTETM) implemented by trained operators certified by the 
manufacturer, Echosens, and monitored on site and remotely by our clinical 
partners, our CLC staff including a study nurse practitioner, our study 
physician, and an independent medical monitor. 
6.7 The primary research site for storage and analysis of biospecimens and 
other data will be the human laboratory at the Center for Alcohol and 
Addiction Studies (CAAS) at Brown University, School of Public Health, 121 
South Main Street, 4th floor, Providence, RI, 02903. The section on data 
safety monitoring gives more information. 
6.8 Visits are expected to be completed at CEHC at 60 Valley Street in 
Providence RI, or through Brown Medicine primary care clinics or similar, 
though the availability of our laboratory offices at 121 S. Main Street, 
School of Public Health provides additional flexibility in the case of 
unforeseen interruptions in access to appropriate space and resources to 
complete the research protocol as described herein.  
6.9 Fidelity (adherence) monitoring via Motivational Interviewing Treatment 
Integrity coding system (MITI Coding Manual 4.1; Moyers, Manual, & Ernst, 
2014) will evaluate the degree to which the intervention is delivered by the 
interventionist(s) as intended with consistency across randomized groups. 
Global ratings include two relational components, i.e., partnership and 
empathy, rated from 1 to 5, with 5 indicating better adherence. Technical 
components, i.e., cultivating change talk and softening sustain talk, will also 
be given global ratings. Finally, behavior counts will be used in the context 
of supervision to monitor the interventionist skill level and identify any areas 
for improvement. This process typically includes coding 10-minute 
segments of a random selection of sessions. Our goal is to exceed that 

 
Page 10 of 21 
 
 
standard and code 10-minute segments for all 40 sessions for all 40 
randomized participants (i.e., one session per participant). Following best 
practices, two raters will use the MITI coding system to maximize and 
assess the reliability of the MITI for assessing intervention integrity, 
including both relational and technical components. Supervision is 
implemented via audio recordings of interviews, and an option to opt out of 
audio recording is included on the bulleted consent form. 
6.10 N/A. There are no plans for a long-term followup.  
6.11 N/A. The study does not test a Humanitarian Use Device (HUD). 
7.0 
Data and Specimen Banking 
7.1 Data and specimens will be banked for future use. Specimens will be stored 
at Brown's SPH lab until they are used for research purposes or discarded. 
The specimens will be accessed by primary members of the research team 
and core lab staff. Future use may involve sending the specimens to clinical 
and/or research laboratories outside Brown for the purpose of performing 
further testing, assays, and similar functions. 
7.2 The data to be stored with each specimen include study ID number, date of 
collection, and visit number, where applicable.  No personal identifying 
information is stored with study specimens under any circumstances.   
7.3 The specimens will remain under the control of the researchers and will not 
be released to outside parties. 
8.0 
Sharing of Results with Subjects 
8.1 The conditions for sharing results with subjects and others is described via 
an interactive informed consent process including a conversation with a 
trained research team member supplemented by a bulleted consent form. 
The bulleted consent form includes a section on “Your Liver Results” which 
describes procedures for random assignment in plain language. 
Participants who are not randomly selected to receive their results at the 
randomization visit in the context of the brief intervention can be given 
these results at the end of their followup visit upon request. These results 
are prepared in a report that includes information provided in standard 
medical practice, such as in a health portal report. Participants are free to 
share these results with their primary care physician together with a copy of 
our bulleted consent form which provides information about the study 
procedures and contact information for the researchers. Participants are 
told, “…our doctor who specializes in liver health reviews your scan results. 
If the scan shows cause for concern, we will tell you and give you a copy to 
give to your doctor. If you do not have a doctor, we can help you find one. If 
our liver doctor thinks you need to go to a specialty liver clinic, we will help 
you make an appointment.” 
8.2 Trained staff inform potential participants of what will happen if blood tests 
for Hepatitis B and/or C return positive results. If these tests are positive, 
the findings will be reported to the Rhode Island Department of Health as 
required by State law. This information is kept confidential by the 
Department of Health and is used to track diseases. This information is 
provided verbally and in writing on the bulleted consent form. 

 
Page 11 of 21 
 
 
8.3 At the conclusion of this research study, the results will be shared with the 
clinics and communities who participate. There are opportunities for 
collaborative dissemination via local, regional, and national presentations, 
as well as publication in academic journals or other appropriate outlets. 
Individual names or any other personally identifiable information for 
participants or those screened for research participation are never included 
on presentations or publications. 
9.0 
Study Timelines 
9.1 The duration of an individual subject’s participation is typically less than 45 
days, with flexibility to accommodate scheduling. 
9.2 The end date of the 11-month project period is July 31, 2025. The strict 
timeline for the entire project and period of award is dictated by this 
supplement funding mechanism as indicated by the National Institutes of 
General Medical Sciences Funding Opportunity Announcement and our 
Notice of Grant Award which is provided with this application.  
9.3 Given this limited timeline, the funder has required that the IRB approval be 
reported to the sponsor no later than November 3, 2024. The Notice of 
Grant Award attached with this application indicates that failure to receive 
IRB approval by this date could result in suspension and/or termination of 
the funding for this supplement award. 
9.4 Primary analyses are expected to be completed within one year of 
enrollment of the final participant and within two years after the date of 
approval for research activities to commence.  
10.0 Inclusion and Exclusion Criteria 
10.1 Screening procedures, described in the relevant section on recruitment 
methods, include medical record reviews for alcohol intake and body mass 
index, as well as age and medical conditions or other conditions which are 
exclusionary as described below. Prescreening questions and the 
associated script are provided in an attachment. 
10.2 Inclusion Criteria. To be eligible, the interested volunteer MUST meet all the 
following:  
● Be at least 21 years of age. 
● Exceed alcohol intake diagnostic guidelines for MetALD. 
● Have a Body Mass Index (BMI) >=25 kg/m2. 
● Be able to speak and read English or Spanish to provide written 
informed consent and understand written and oral instructions in 
English or Spanish. 
10.3 Exclusion Criteria. To be eligible, the interested volunteer MUST NOT have 
any of the following: 
● Pre-existing liver disease or hepatocellular carcinoma or prior liver 
transplant. 
● Pre-existing medical conditions that, in the opinion of the 
investigative team, would interfere with research participation 

 
Page 12 of 21 
 
 
(e.g., loss of kidney function, uncontrolled infections, multiorgan 
failure, uncontrolled upper gastrointestinal bleeding, other active 
malignancies except skin cancer). 
● Pre-existing mental health conditions that, in the opinion of the 
investigative team, would interfere with the ability to provide 
informed consent and understand written and oral instructions 
(e.g., hepatic encephalopathy, psychotic disorder diagnosis or 
symptoms). 
● Current pregnancy. 
● Be anyone who, based on self-reported withdrawal symptoms and 
the opinion of the investigative team, could not currently safely be 
withdrawn from alcohol without medical detoxification. 
● Currently receiving formalized psychosocial treatment for an 
alcohol use or drug problem and/or newly taking medications for 
an alcohol use or drug problem. 
● Currently receiving formalized behavioral weight management 
treatment and/or currently taking weight loss medications.  
10.4 The research study will exclude anyone who is not an adult, pregnant 
persons, anyone who is determined to be or suspected to be unable to 
consent for research participation and will not recruit from prison settings.  
11.0 Vulnerable Populations 
11.1 N/A. The research is not anticipated to involve individuals who are 
vulnerable to coercion or undue influence or special populations. 
12.0 Local Number of Subjects 
12.1 This pilot aims to randomize 40 participants to standard (n=20) and 
enhanced (n=20) conditions, with randomization stratified by relevant study 
variables. 
12.2 It is anticipated that ~80 interested volunteers may complete informed 
consent prior to in-person screening to confirm eligibility, allowing for 
ineligibility and disinterest after screening. 
13.0 Recruitment Methods 
13.1 The primary recruitment location is our nonprofit partnering clinic, Clínica 
Esperanza/Hope Clinic (CEHC) at 60 Valley Street in Providence, RI. The 
CEHC mission, patient population, and resources are described below. 
Potential participants may also be recruited from the community or via 
digital outreach with prescreening completed by phone or online with 
Brown-approved survey software. Procedures may also be implemented at 
our main laboratory at 121 S. Main Street, Providence, RI. 
13.2 Patient navigators, i.e., Navegantes, are trained community health workers 
assisting with patient care and outreach for CEHC. The assistance of 
Navegantes with participant recruitment and retention is key to the success 
of this research. Study information will be posted and placed in exam 
rooms, waiting rooms, check-in/checkout windows, and any other locations 

 
Page 13 of 21 
 
 
within the clinic or in the surrounding community which prospective 
participants congregate.  
13.3 Review of the electronic health record (EHR) identifies patients age 21+ 
years with current drinking levels and body mass index (BMI) placing them 
at risk for downstream health complications including MetALD. EHR 
reviews involving access to personally identifying information is necessary 
to complete the research. A waiver of HIPAA consent is requested via 
Appendix G attached with this protocol. Where medical history is available 
in the record, obvious exclusions are identified (e.g., current pregnancy, 
Hepatitis B/C diagnosis, prior liver transplantation; see Inclusion/Exclusion 
criteria for a full list of exclusionary criteria). Where feasible, brief alcohol 
screening via the 3-item Alcohol Use Disorder Identification Test-
Consumption subscale (AUDIT-C) is included as part of patient care. The 
AUDIT-C items, description, and references are provided in an attachment. 
Generally, the higher the AUDIT-C score, the more likely it is that the 
patient’s drinking is affecting their health or safety.  
13.4 Patients who may be suitable for the study and who have visits scheduled 
in advance may be sent a letter informing them that Brown University is 
recruiting patients in the clinic for a research study. In clinic, patients are 
invited by their health provider, patient navigator, or Brown University 
research team member to answer a limited set of prescreening questions to 
see if the study may be suitable for them. Prescreening questions are in 
plain language, with many asked in an easy to answer yes/no format. For 
example, “Are you able to read English or Spanish?” The pre-screening 
questions and corresponding semi-structured script are provided in an 
attachment. Potential participants who complete pre-screening may be 
offered a nominal gift (e.g., a pen, notepad, water bottle) or meal as a 
gesture of appreciation, consistent with best practices for community 
engaged research. 
13.5 If patients are unable to participate in the prescreening at the time of their 
clinic appointment, prescreening can be completed over the phone or 
deferred until their next clinic visit. In this case, permission would be 
requested to remind the patient of their upcoming appointment by common 
methods (e.g., phone, mail). Potential participants who hear about the study 
by word of mouth or advertisements in the community or online may also 
contact the study team by phone, text, or online to hear more about the 
study and answer the pre-screening questions. In the case of digital 
outreach with online prescreening, Brown-approved survey software (e.g., 
Qualtrics or similar) will be used and will include a study landing page that 
provides enough information to describe study procedures to allow potential 
participants to decide about their interest in continuing with prescreening. 
Questions used for online prescreening are the same as those provided in 
the attachment for phone prescreening and also include the AUDIT-C 3-
item alcohol screening measure. 
13.6 Following pre-screening, participants will continue with informed consent for 
research participation prior to further screening to confirm eligibility. This 
last stage of screening includes a blood draw for quantification of liver 
function and cardiometabolic factors using standard clinical liver, metabolic, 
and lipid panels, HbA1c, and Hep B/C testing if not already performed (see 

 
Page 14 of 21 
 
 
Exclusion criteria), as well as a timeline followback interview to assess 
recent alcohol consumption with high precision. 
13.7 To facilitate recruitment and retention, a secure (e.g., Filemaker or similar, 
Brown-approved software tracking system) tracking database is accessible 
via an internet connection at CEHC and our Brown University laboratory 
offices. The tracking database separately stores screening and participant 
information and can automatically generate study milestones, task reminder 
emails for staff, and follow-up appointment scheduling and reminders. 
Given that the target patient population may not have regular access to 
internet, email scheduling and reminders only supplement efforts of the 
research team to contact participants by phone or via in-person 
interactions. Close-contact locators (e.g., spouse, adult children age 18+, 
close friend) will facilitate future contact. Obtaining contact information for 
close-contact locators is necessary to complete the research as 
underresourced participants may not have reliable phone service, internet 
access, or stable home address. Obtaining locator information is standard 
practice for research studies working with underresourced and marginalized 
populations. Research team members stay in touch with participants 
regularly to promote attendance to the study protocol. The CEHC 
Navegantes will assist with scheduling participant appointments and 
following participants through the protocol offering support, reminders, and 
ample opportunities for interfacing with the study team. Together, these 
procedures maximize recruitment and retention through minimizing missed 
appointments and attrition.  
13.8 All study advertisements and recruitment materials using the Brown 
University School of Public Health logo are required to have approval, and 
appropriate approval will be obtained prior to implementation. Brown 
university guidelines for teaser and print advertisements will be followed. 
Print advertisements will include all required information and be similar to 
the one attached. 
13.9 Compensation procedures will be described to participants during the 
informed consent process. Compensation amounts and the timeline for 
payments is provided in the bulleted consent form attachment. Interested 
volunteers are provided $30 for in-person screening, paid regardless of 
eligibility. Participants are paid $150 for the randomization visit and $150 for 
the followup visit. Total possible compensation is $330. Brown university 
policies and procedures for applying cash payments will be followed with 
required documentation. Transportation to study visits can be provided at 
no cost to the participant through Brown-approved and SPH-approved 
services (e.g., Lyft concierge), public transportation passes, or similar 
methods. For procedures where participants must arrive fasting (e.g., no 
food for 3+ hours for Fibroscan®), a meal will be provided. Meals or snacks 
may also be provided at recruitment events at partnering clinics or other 
community sites that are easily accessible to the population served. 
14.0 Withdrawal of Subjects 
14.1 Anticipated circumstances under which subjects will be withdrawn from the 
research without their consent include instances of repeated missed 
appointments, apparent intoxication upon arrival to study visits, 

 
Page 15 of 21 
 
 
inappropriate behavior of any kind toward staff on our team, or similar 
circumstances. Participants arriving to appointments intoxicated may be 
rescheduled or may be terminated from the study, with this decision made 
by the primary researcher on this protocol.  
14.2 Participants who choose to withdraw from the study may do so for any 
reason without penalty to them and will be paid for their participation to that 
point. During the informed consent process, the choice of participants to be 
in research or to stop participating at any time is explained verbally and in 
written form on a bulleted consent document. It is imperative that patients 
do not feel pressure to participate and understand the study is voluntary. 
The participant may discontinue participation at any time without penalty or 
loss of benefits to which the subject is otherwise entitled.    
15.0 Risks to Subjects 
15.1 Study procedures pose minimal risks. The bulleted consent form and 
informed consent process describes foreseeable risks and discomforts to 
the participations because of being in this study.  
15.2 Potential risks to human subjects participating in the proposed research are 
minimal and include as follows: 
● Breach of confidentiality.  
● Psychological discomfort from answering questions about lifestyle 
behaviors such as diet, exercise, and alcohol intake. 
● Physical risks associated with blood draw procedures including 
and not limited to pain or discomfort, venipuncture, or fainting. 
● Physical or emotional risks associated with liver screening and 
receiving liver-health feedback. 
● Risk of coercion. 
15.3 
N/A, procedures which may have unforeseeable risks are not expected. 
15.4 
N/A, pregnant persons are excluded from the research study. 
15.5 
N/A, risks to others who are not subjects are not expected.  
16.0 Potential Benefits to Subjects 
16.1 Free, noninvasive liver screening and brief behavioral intervention has 
potential to reduce risks of liver biopsy and other invasive assessments or 
interventions in the context of progressive liver damage, thereby reducing 
the participant’s health risks and discomforts, which is a potential benefit. 
16.2 Individual participants are unlikely to have any other direct benefits of being 
in this study. 
17.0 Data Management and Confidentiality 
17.1 Plans for analyzing the data will be included on clinicaltrials.gov following 
established timelines and requirements set by the National Institutes of 
Health. Piloting procedures in randomized clinical trials serves many 
valuable functions including gauging feasibility of recruitment, piloting 
randomization procedures, comparing intervention-specific retention rates, 

 
Page 16 of 21 
 
 
withdrawal rates including reasons for withdrawal, and intervention-specific 
fidelity rates. A CONSORT diagram will describe the screening and 
enrollment process implemented and demonstrate feasibility. To examine 
the acceptability of SBIRT/P procedures, quantitative and qualitative 
measures of satisfaction with Fibroscan® screening and of the brief 
motivational intervention will be analyzed.  
17.2 Multiple protections will be implemented to secure the data and minimize 
risk of breach of confidentiality, including (a) training and authorization of 
access: limiting access to personally identifiable information to personnel 
with appropriate and up to date human subjects training who are 
supervised by the investigative team and reminded to keep information 
confidential, (b) password protection and encryption: digital and hard-copy 
data securely in accordance with data integrity standards using Brown CIS-
vetted and approved software and servers, (c) physical controls and 
separating identifiers and data: storing personally identifiable information 
separately from data or biological specimens in locked locations designated 
for this purpose and coded with a unique ID number that is not directly 
associated with the participant (e.g., not a birth date), (d) certificate of 
confidentiality: explaining during informed consent verbally and in writing 
that the study has obtained a certificate of confidentiality (CoC) from the 
National Institutes of Health, as well as informing potential participants 
verbally and in writing during informed consent about the limitations of 
confidentiality including the limitations of the CoC and instructing 
participants to protect their own information. 
17.3 Procedures that will be used for quality control of collected data will include 
working from highly detailed project manuals and standard operating 
procedures that are followed with line-by-line checks for all procedures. The 
project coordinator or team member in a similar supervisory role will review 
hard-copy data for errors and document digitally or in writing that this 
oversight was conducted including the date and name of the person 
conducting the check. 
17.4 Data and specimens will be banked for future use following best-practice 
guidelines to ensure integrity and confidentiality of the samples.  
● Once collected, specimens will be stored at our designated 
laboratory space at Brown SPH until they are used for research 
purposes or discarded.  
● The specimens will be accessed by primary members of the 
research team and core lab staff.  
● Future use may involve sending the specimens to clinical and/or 
research laboratories outside Brown for the purpose of performing 
further testing, assays, or similar functions. 
● The data to be stored with each specimen include study ID 
number, date of collection, and visit number, where applicable. No 
personal identifying information is stored with study specimens 
under any circumstances.   
● The specimens will remain under the control of the researchers 
and will not be released to outside parties. 

 
Page 17 of 21 
 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
18.1 N/A. This section is not required when research does not involve more than 
minimal risk to participants. 
19.0 Provisions to Protect the Privacy Interests of Subjects 
19.1 All interviews, exams, and sessions will be conducted following applicable 
human subjects research protections privacy standards including 
conducting these in a manner and space that ensures privacy and 
confidentiality of information. Private identifiable information associated with 
research data will be available only to research personnel who have been 
trained in human subjects’ protection guidelines and are certified by the 
Collaborative Institutional Training Initiative (CITI) as mandated by the 
Brown University IRB. Deidentified data will be indexed by numeric codes 
which are sequentially generated numbers that are not derived from private 
identifiable information. 
19.2 CEHC is an active clinic serving uninsured individuals as described in other 
relevant sections herein. The CEHC employs Patient navigators, i.e., 
Navegantes, who are trained community health workers assisting with 
patient care and outreach for CEHC. Navegantes are key to the success of 
this research, as they are a trustworthy and familiar presence in the clinic. 
Navegantes will assist with a warm hand-off where applicable, i.e., from 
clinic staff to research staff. Participants are informed that they have the 
right to decline to answer a particular question that feels too uncomfortable. 
By conducting study procedures in a more familiar setting (i.e., CEHC), the 
goal is to increase participants’ comfort and sense of agency.      
19.3 The research team will access information about the participant via the 
medical record, the participant’s self-report, biometric measurements, and 
laboratory and clinical tests collected to complete the study aims. Only 
primary members of the research team are permitted to access participant 
research data following the required standards to uphold data integrity. 
20.0 Compensation for Research-Related Injury 
20.1 N/A. The research does not involve more than minimal risk, and there is not 
available compensation in the event of research-related injury.  
21.0 Economic Burden to Subjects 
21.1 N/A. Participants are not expected to be responsible for any costs involved 
in their participation in the research. 
22.0 Consent Process 
22.1 The informed consent process will adhere to the procedures described in 
HRP-090-SOP.  
22.2 The process for informing potential participants about the study and 
obtaining their consent for participation will take place in person in a private 
space and will be documented in writing using a bulleted consent form that 
is signed with a digital or wet signature by study participants and witnessed 
by staff on our team.  

 
Page 18 of 21 
 
 
22.3 After the procedures are described to the potential participant, they may 
take time to think it over prior to signing. If the potential participant remains 
interested after having time to consider the research, we will make them an 
appointment to continue. 
22.4 Ongoing consent is supported through informing participants that 
participation is voluntary at each study visit.  
Non-English Speaking Subjects 
● 
All study procedures may be implemented in either Spanish or 
English. Prescreening questions include asking whether the potential 
participant can read Spanish or English. Those who cannot speak 
either of these languages will not be eligible to complete informed 
consent for research participation and cannot enroll in this study. 
Participants must speak, read, and understand, Spanish or English to 
be eligible. 
● 
For monolingual Spanish speakers, all procedures and materials will 
be supplied in Spanish. For participants who are bilingual and prefer 
procedures implemented in Spanish, all study procedures and 
materials will be supplied in Spanish.  
● 
Where feasible, self-report, validated measures are sourced from 
published versions or translated professionally (e.g., Language 
connections or similar professional service). Bulleted consent forms, 
advertisements, and other lengthy forms or study materials that would 
be costly to have professionally translate are translated by a native 
Spanish speaker who is a member of our research team and reviewed 
for clarity by a second native Spanish speaker. 
23.0 Process to Document Consent in Writing 
23.1 Informed consent documentation will adhere to the procedures described in 
HRP-091-SOP using a bulleted consent form with digital or wet signature 
from the potential participant witnessed by a trained staff member. 
24.0 Setting 
24.1 The settings where we will conduct the research include Clínica 
Esperanza/Hope Clinic (CEHC) at 60 Valley Street in Providence, RI, with 
the capability to conduct study visits at our primary offices at Brown 
University SPH 121 S. Main Street in Providence, RI, as well. Our team 
also has the capacity to reach potential participants through digital and 
community outreach.  
24.2 CEHC was founded in 2007 as a place for patients, volunteers, community 
partners, and donors to be healthy. CEHC’s community health care model 
ensures that quality care comes from caregivers who are fully integrated in 
the community. Our partnership between Brown University and CEHC 
teams will enable us to reach the target underserved population at risk for 
MetALD.  
24.3 CEHC focuses on providing high-quality, culturally attuned, and 
linguistically appropriate healthcare to all uninsured adults in Rhode Island. 
CEHC’s patient base is primarily made up of Spanish-speaking, Latinx 

 
Page 19 of 21 
 
 
immigrants from Central and South American countries. CEHC has a core 
paid staff and a robust network of volunteer medical providers, nurses, 
medical interpreters, and non-provider volunteers. More than 4,000 patients 
across nearly 7,000 visits are served annually. CEHC has recently 
expanded their space, now occupying three suites in the Valley Street 
location where recruitment will take place.  
24.4 CEHC serves a diverse population with significant unmet healthcare needs, 
including those with alcohol intake and overweight or obesity placing them 
at increased risk of MetALD. Of CEHC’s current patient population, 92% 
are Latinx, primarily from Central and South America, and 90% are Spanish 
speaking. Many patients experience immigration-related stress. Many also 
face instrumental barriers to care, with 4 out of 5 patients living well below 
the poverty line. More information can be found on CEHC’s website, 
www.aplacetobehealthy.org. 
24.5 CEHC is paid through a consultancy for this funded research project. 
Appropriately compensating clinical partners is best practice for community 
engagement. CEHC’s consultancy fee, approved by their organization, 
Brown University, and the National Institute of General Medical Sciences, 
accommodates the use of CEHC resources, including supplies, space, and 
staff time. Patient navigators, i.e., Navegantes, are trained community 
health workers assisting with patient care and outreach for CEHC. The 
assistance of Navegantes with participant recruitment and retention is key 
to the success of this research. Seamless integration into clinic operations 
and culturally appropriate approaches are key to successfully reaching 
underresourced communities.  
25.0 Resources Available 
25.1 There are ample resources available to conduct the research. Data 
showing the number and demographics of the patient population served by 
the CEHC provides evidence for the feasibility of recruiting the designated 
40 randomized participants within the timeframe expected. The CEHC 
serves over 4,000 patients over 7,000 visits annually. Patients commonly 
have indications of cardiometabolic disease, e.g., hypertension (59%), 
diabetes (41%), and hyperlipidemia (22%). The CEHC has integrated the 
AUDIT-C screening tool into their clinical procedures, allowing the research 
team to identify prospective participants based on BMI and alcohol use. 
Therefore, this study should meet or exceed the goal of recruiting 1 or 2 
participants per week to obtain a final sample of 40 randomized participants 
in the limited project period. Moreover, the research team is fully prepared 
to expand recruitment through community or digital outreach and conduct 
study procedures at our Brown SPH laboratory should it be necessary to 
meet enrollment targets.   
25.2 The research team includes experienced members in multiple roles (e.g., 
research assistants, project coordinator, medical laboratory technician, 
faculty investigators, licensed practitioners, interventionists) contributing 
effort to the project at our partnering sites, in team meetings, in our 
laboratory, and in related preparations and efforts. The combined effort 
devoted to this project for the research team triples the project period or 
more, indicating a very high level of effort committed by the team.  

 
Page 20 of 21 
 
 
25.3 The research team from Brown will be partnering primarily with the clinical 
facility described above, the Clínica Esperanza/Hope Clinic (CEHC), which 
occupies three suites in fully remodeled space in the Olneyville 
neighborhood in the city of Providence. The CEHC is a highly active clinic 
providing holistic care including primary medical care, specialty clinics, and 
related services (e.g., food pantry, community clothing closet) to adults 
without insurance in Rhode Island. The CEHC has earned the Gold 
Standard of Care from the National Association of Free and Charitable 
Clinics and has earned the highest levels of financial transparency awarded 
to charitable organizations. The Brown SPH facilities occupy three office 
floors of the 121 S. Main building, where our research team has offices, 
cubicles, meeting spaces, laboratory space, and usage of the third-floor 
laboratory preparation room. 
25.4 In case of emergency, emergency medical services (EMS) will be called. 
Participants found to be experiencing medical or physical events that do not 
require emergency medical services will be evaluated by the study 
physician or another medical provider at partnering clinical sites or at 
Brown. An advantage of conducting the study activities at the partnering 
site is the wealth of clinic and medical staff available to assist in the event 
of a medical or physical event. In any case, the participant will be 
encouraged to seek medical care as appropriate.  
25.5 In case of an emergency psychiatric event that presents imminent risk of 
harm to the participant or others, emergency medical services (EMS) will be 
called. Any participant who is found to be experiencing a psychiatric or 
psychological issue that is of concern and possible imminent risk will be 
evaluated by Dr. Treloar Padovano, a licensed clinical psychologist in 
Rhode Island, or one of several other licensed clinicians on the team.  
25.6 The target population at risk for MetALD is also at risk for known or 
emergent medical issues or events that are not likely to be due to 
participation in the minimal risk research study. These include but are not 
limited to events such as hospitalization due to an alcohol-related injury or 
detoxification from alcohol, hypertension or heart palpitations, or 
emergencies related to medical events or accidents.  
25.7 Processes to ensure that all persons assisting with the research are 
adequately informed are as follows: 
● All team members complete thorough training on the protocol and 
procedures consistent with their duties on the project. Team 
members complete CITI training prior to research engagement as 
well as EHS biosafety training where indicated. 
● Weekly team meetings, or more frequent meetings at some 
stages of training and data collection, ensure that staff are closely 
supervised and obtain a high level of proficiency.  
● Individuals conducting the Fibroscan® are trained operators 
certified by Echosens, the manufacturer of our Fibroscan® 
ultrasound machine. Individual Fibroscan® results are reviewed 
by a study physician who will instruct the team on appropriate next 
steps and referrals.  

 
Page 21 of 21 
 
 
● Sessions with the study counselor are audio-recorded with 
sections selected at random for review and coded by supervisors 
to ensure fidelity to the intervention protocol. Interventionists are 
supervised at a minimum biweekly and typically weekly and are 
given feedback on adherence to the protocol.