Biobehavioral Pathways Underlying Alcohol Use and Health
Phase: NA
Conditions: Alcohol Use Disorder, Liver Diseases
Sponsor: Brown University

ClinicalTrials.gov Identifier: NCT05135767
ID: 2011002840
Biobehavioral Pathways Underlying Alcohol Use and Health
NCT05135767
Biobehavioral Pathways Underlying Alcohol Use and Health
Sponsor:
Brown University
Collaborators:
National Institute of General Medical Sciences (NIGMS)
Rhode Island Hospital
Information provided by (Responsible Party):    
Brown University
05/25/2023
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Brown University
Human Subjects Research Application
Instructions on how to complete this application can be found in our guidance tool.
Study Title:  Biobehavioral Pathways Underlying Alcohol Use and Health
Principal Investigator: Hayley Treloar Padovano, PhD 
If PI is a graduate/medical student, please upload Appendix I: Human Subjects Research Advisor. 
1. Provide the scientific background of the study.
Alcohol-associated liver disease (AALD) and alcohol use disorder (AUD) are intersecting diseases.
This project unites a team of Brown and Lifespan researchers to demonstrate the feasibility of
implementing a brief, psychosocial AUD intervention in patients with AALD and AUD. The
intervention includes personalized feedback from liver function tests, interviews of drinking
patterns, and self-monitoring of craving for alcohol and negative mood states via smartphone reports
in daily life.
2. Identify the research question(s) of the study and how the study will contribute to
generalizable knowledge.
We will compare groups of participants; half will have AALD and AUD, and half will have AUD
only. There is a 1-week screening phase, brief intervention followed by 3-week intervention phase,
and 3-month follow up. As a feasibility study, the total sample size is small (n = 44; 22 per group).
This project is funded under P20GM130414, an NIH-funded Center of Biomedical Research
Excellence (COBRE).
3. Describe each participant population for the study and list all eligibility criteria.
Drinkers exceeding moderate drinking guidelines in the past 3 months will be recruited from local
clinics and the community.
General Inclusion Criteria. To be eligible, the interested volunteer must:
1.
Be at least 18 years of age.
2.
Meet the Diagnostic and Statistical Manual-5 criteria for alcohol use disorder, indicated by meeting 2 or
more symptom criteria, as assessed using the MINI.
3.
If male, report 14 or more standard alcoholic drinks per week, or if female, report 7 or more standard
alcoholic drinks per week at any point in the 90 days prior to enrollment.
4.
Be able to speak and read English or Spanish in order to provide written informed consent and understand
written and oral instructions in English or Spanish.
General Exclusion Criteria. Interested volunteers must not have any of the following:
1.
Meet the Diagnostic and Statistical Manual-5 criteria for a current diagnosis of psychotic disorders, as
assessed using the MINI.
2.
Currently receiving specialized psychosocial treatment for an alcohol-use or drug problem.
3.
If female, pregnant or nursing.
4.
Be anyone who, in the opinion of the investigative team, could not currently be safely withdrawn from alcohol
without medical detoxification.
5.
A BMI of 40 or more, or 35 or more and experiencing obesity-related health conditions, such as high blood
pressure or diabetes.
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6.
Known medical conditions that, in the opinion of the investigative team, would confound results (e.g.,
uncontrolled infections, multiorgan failure, uncontrolled upper gastrointestinal bleeding, hepatocellular
carcinoma or other active malignancies except skin cancer).
7.
Patients who have received a liver transplant or are too ill to participate.
8.
Pre-existing loss of kidney function with estimated glomerular filtration rate < 30.
9.
Any other condition that, in the opinion of the investigative team, would make the interested volunteer
unsuitable for the study or unable to comply with the requirements.
Additional Inclusion Criteria for AALD/AUD patients.
To be eligible in the AALD/AUD group, the interested volunteer must be diagnosed with advanced alcohol-
associated liver disease (i.e., either alcoholic hepatitis or alcoholic cirrhosis). AALD will be defined by chart review. 
Interested volunteers must have one of the following:
1.
Positive liver biopsy, or
2.
Fibroscan® score > 12.5 kPA, or
3.
Evidence of a nodular liver or portal hypertension on abdominal imaging, or
4.
Presence of portal hypertensive complications such as hepatic encephalopathy, ascites, or varices, or
5.
Fibrosis-4 index (FIB-4) >= 3.25, or
6.
Aspartate transaminase-platelet ratio index (APRI) >= 1.0.
Additional Exclusion Criteria for the AUD-only, comparison group. 
To be eligible in the AUD-only group, the interested volunteer must not show the following diagnostic test results 
indicating advanced, alcoholic fibrosis >=F3.
1.
Fibrosis-4 index (FIB-4) >= 3.25*, or
2.
Aspartate transaminase-platelet ratio index (APRI) >= 1.0**, or
3.
GGT-to-platelet ratio >= 0.32.
*The FIB-4 index will be calculated as: age (years) × AST (IU/L)/platelet count (×109/L) × √ALT (IU/L).
**The APRI score will be calculated as: (AST/upper limit of normal)/platelet count (expressed as
platelets × 109/L) × 100.
3.1 Select all vulnerable populations you intend to target for recruitment.
☐Brown 
Faculty, 
Staff, or 
Students
☐Children (30 
days – 17 
years)
☐Justice-
Involved
☐Decisionally- 
Impaired
☒
At Risk for / 
Experiencing 
Substance Use 
Disorder 
☐Students
☐Known 
Interpersonal 
Relationships
☐At Risk of / 
Experiencing 
Homelessness
☐Unauthorized 
Immigrants
☐
Refugees
☐LGBTQ+
☐Pregnant 
People
☐Fetuses / 
Neonates
☐American 
Indian / 
Alaskan 
Native
☐
Disabled 
People / 
People with 
Disabilities
4. Describe the recruitment methods.   ☐ N/A
Collaborator, Kittichai Promrat, M.D., directs hepatology clinics in Providence, RI, one of which is expected to be 
the primary recruitment site for alcohol-associated liver disease (AALD) patients, i.e., the Lifespan Hepatology 
Clinic. Another is the Providence VA Medical Center, where Dr. Promrat is the Chief of Gastroenterology. The 
project Primary Investigator, Hayley Treloar Padovano, Ph.D., and her research assistant, will work directly with Dr. 
Promrat and fellows and interns under his supervision to facilitate recruitment. Potential participants will be identified 
by chart review at their regular clinic visit using a checklist of criteria.
Under HIPAA, as members of the covered entity, Dr. Promrat and other fellows or interns under the supervision of 
Dr. Promrat may utilize information in medical records as part of routine clinical care to identify potential interested 
volunteers for this research project. Dr. Promrat or another fellow or intern under the supervision of Dr. Promrat 
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will review the Eligibility Checklist for all patients seen in their routine clinical visits. The Eligibility Checklist does 
not include any protected health information, i.e., an individual cannot be identified from the information. 
If the visit is being conducted via telehealth, i.e., over phone or video conference, Dr. Promrat, or a fellow 
or intern under the supervision of Dr. Promrat, will introduce the study to the patient. If the patient is interested 
after hearing about the study, and they give their verbal permission, Dr. Promrat or a fellow or intern under his 
supervision will ask a few initial screening questions. If the patient appears eligible and remains interested, they 
will be scheduled for an in-person screening at Brown University. If the patient is interested but is not able to 
answer the initial screening questions at that time, they may be asked for verbal permission to mail or email them 
a Consent to Contact and Screening form to be completed, signed physically or electronically, and returned to the 
Brown University research study.
We may ask prospective participants who meet basic eligibility criteria to self-report to us whether they 
have been diagnosed with alcohol-associated liver disease, prior to the in-person screening session, and if so, 
what clinic and/or provider oversees their care. This procedure supplements our efforts to identify participants 
directly through their medical records at our participating clinic(s). Prospective participants with alcohol-associated 
liver disease who are recruited from the community based on their self-reports will complete the currently 
approved Brown HIPAA authorization form at their in-person screening session or via Brown-approved DocuSign 
to confirm their liver diagnosis. This will enable us to request records from the clinics and/or providers they identify 
that can confirm the specific eligibility criterion of advanced, alcohol-associated liver disease.
If the patient is in the clinic for an in-person visit, Dr. Promrat, or a fellow or intern under the supervision of 
Dr. Promrat will introduce the study to the patient. If the patient is interested after hearing about the study, Dr. 
Promrat, or a fellow or intern under his supervision, will offer the patient the option of signing a Consent to 
Contact and Screening form, HIPAA Authorization Form, and Medical Release Form. The Consent to Contact and 
Screening form gives permission for the interested volunteer’s contact information (i.e., name, phone number, and 
email address) to be shared with the Brown University research study. This form also gives permission for a study 
representative to ask initial screening questions in the clinic, over the phone, or via video conference. Interested 
volunteers who are not able to meet with the study representative the day of their clinic visit will be given the 
option to meet with the representative at their next visit or be contacted by a study representative over the phone 
or via video conference. They will also be given the option to access our study landing page and initial screening 
survey online via Brown-approved Qualtrics. Interested volunteers who appear to be eligible based on the initial 
screening, via either in-person, phone, videoconference, or online-survey methods will be invited to the Brown 
laboratory for an in-person screening to confirm eligibility. 
The HIPAA Authorization Form and Medical Release Form are required to share protected health 
information from the medical record with the Brown University research study. This information is necessary to 
characterize patients who are recruited to the study. The HIPAA Authorization Form and Medical Release Form 
may be signed at any time but must be signed before protected health information from the medical record can 
shared with the Brown University Research Study. 
The AUD-only comparison group will be matched on drinking level. Interested volunteers will be enrolled at 
a pace to match recruitment of AALD/AUD patients. The AUD-only group will be recruited via a variety of standard 
tactics for research projects conducted by our investigative team. These will include the following:
1.
Posting print or digital advertisements via flyers in local businesses (with permission) and other public
places, such as public kiosks, the Department of Motor Vehicles, and community boards.
2.
Posting advertisements on social media.
3.
Posting advertisements via other methods of media, such as newspaper and radio advertisements.
4.
Posting advertisements on public transportation.
5.
Posting flyers in socioeconomic disadvantaged areas.
6.
Sending mailings to local health-care professional offices describing the study and providing flyers that can
be placed or posted in their waiting rooms.
Initial Screening. Interested volunteers may respond to recruitment advertisements by completing a set of
pre-screening questions online (i.e., Qualtrics) or they may respond to recruitment materials by phone, email, or 
text message. Those who complete the online pre-screening questions will be asked to leave contact information 
including their phone number and email address, as well as their contact preferences. Interested volunteers who 
complete the online pre-screening and appear eligible will be contacted to complete a phone or video conference 
(i.e., Zoom) screening. Those who appear eligible will be invited to schedule an in-person screening in our laboratory 
at 121 South Main Street, Providence, RI. All aspects of this study protocol including all recruitment and screening 
materials and procedures will be offered in English or Spanish, at the preference of the participant. As described 
above, two postdoctoral interventionists who are fluent in English and Spanish will deliver the intervention and may 
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also assist with screening and recruitment. Any information collected as part of online pre-screening or phone or 
video conference (i.e., Zoom) screening prior to receiving written informed consent will be stripped of any personally 
identifiable information and will be saved only for the purposes of tracking feasibility of screening, recruitment, and 
enrollment. 
In-Person Screening. All interested volunteers who appear to be eligible based on an initial screening will 
be invited to the CADRE laboratory at 121 South Main Street, Providence, RI, for an in-person screening to confirm 
eligibility. In-person screening processes will follow written informed consent, and all in-person screening data 
saved for research purposes will be safeguarded as attested herein.
5. Explain the informed consent process.   ☐ N/A
Overall Process. Informed consent for in-person screening and participation will be obtained at the in-
person screening session at CADRE laboratory at 121 South Main Street, Providence, RI. Interested 
volunteers will be given the opportunity to read an informed consent document in a private exam/assessment 
room. After the interested volunteer has verbally stated that they have read the informed consent document, 
the research assistant will review the document with the interested volunteer, highlighting each bullet point 
and soliciting questions from the interested volunteer at pre-specified checkpoints. A breathalyzer test will be 
administered prior to the interested volunteer signing and dating the informed consent document, and a 
reading of .000 will be required prior to obtaining the potential participant’s signature. The research assistant 
will witness informed consent signing with their own written signature and date. In order to ensure voluntary 
participation and minimize possibility of coercion or undue influence, the research assistant will take care to 
highlight that (1) involvement in research is entirely voluntary, (2) the interested volunteer can withdraw from 
the screening process or participation in the research at any time, and (3) the interested volunteer is 
welcomed to ask questions at any point during their research involvement. Those who express hesitation to 
proceed with any portion of the in-person screening or study protocol will be reminded that participation in 
research is entirely voluntary and that they may withdraw at any time. Participants who indicate a desire to 
withdraw from the study will be compensated for their participation to that point. The research assistant will 
have completed all applicable CITI and HIPAA training and will be trained by the PI in informed consent 
procedures. Facilitate Understanding. The start and stop time of the informed consent procedures will be 
documented on a project manual with the research assistant’s initials to ensure that adequate time was taken 
to provide informed consent and review the consent document. Interested volunteers will be encouraged to 
ask questions throughout the informed consent process at pre-specified checkpoints. Those who provide 
written informed consent and proceed with the study protocol will be encouraged to ask questions at each 
study visit.  We plan to oversample individuals of Hispanic ethnicity and expect approximately one-third of our 
participants will be of Hispanic ethnicity. Therefore, the research assistant will be fluent in both English and 
Spanish, and all aspects of the informed consent process, including the informed consent document, will be 
available in both English and Spanish. Interested volunteers will be required to have ability to read and 
comprehend the informed consent document in either English or Spanish. Comprehension will be assessed 
via a short, 4-item quiz assessing understanding of key aspects of the study procedures. The quiz will be 
embedded in the informed consent document, which is attached with this IRB application. Documentation. 
The interested volunteer will provide their written signature on the informed consent document. The research 
assistant will witness informed consent signing with their own written signature and date. The original signed 
consent form will be kept in a locked filing cabinet separate from any data, and the potential participant will be 
offered a copy of the signed form. 
5.1 To request a waiver or alteration of consent, at least one box must be checked   ☒ N/A
☐The research involves public benefit and service programs, is conducted by or subject to the
approval of state or local officials, and could not practicably be carried out without the waiver
or alteration;
☐The research meets all requirements for a general waiver or alteration of consent
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☐ For the purpose of screening, recruiting, or determining eligibility of prospective participants, 
the investigator will obtain information or biospecimens either through oral or written 
communication with participants, or by accessing records or stored identifiable biospecimens.
5.2 To request a waiver of documentation of consent, at least one box must be checked   ☒ N/A
☐ The only record linking the subject and the research would be the informed consent form and 
the principal risk would be potential harm resulting from a breach of confidentiality.
☐ The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context.
☐ Participants or legally authorized representatives are members of a distinct cultural group or 
community in which signing forms is not the norm, the research presents no more than 
minimal risk of harm and there is an appropriate alternative mechanism for documenting that 
informed consent was obtained.
6. Describe if the study design involves deception or incomplete disclosure.   ☒ N/A 
Click or tap here to enter text.
7. Describe the study procedures.   
If study procedures involve asking participants about depression, suicide, or the risk of harm to self 
or others; may result in participants experiencing emotional distress; include populations at high 
risk for self-injury; administer study medications with a side effect of suicidal ideation, or involve 
other research components that could increase suicidal risks, please upload Appendix F: Mental 
Health Safety Plan.
7.A. Overall Design. 
This prospective, two-arm intervention trial will include drinkers who exceed moderate drinking guidelines (n = 44; 
i.e., 7 or more drinks per week for women and 14 or more drinks per week for men, at any point in the past 3 
months) recruited from local hospitals, clinics, and the greater community. We will aim to recruit 22 patients with 
alcohol-associated liver disease (AALD) and alcohol use disorder (AUD) and 22 with AUD only, oversampling 
women and individuals of Hispanic ethnicity. Biological sex, Hispanic ethnicity, and age and BMI will be a priori 
covariates. Patients with other confounding factors will be excluded as indicated in Section 3 above. In the AUD-
only comparison group, indices of liver fibrosis available from routine diagnostic blood tests will rule out AALD and 
non-alcoholic liver disease. Drinking will be corroborated with timeline follow-back, direct ethanol (EtOH) biomarkers 
from blood, urine, and breath collected in the laboratory, and self-monitoring via ecological momentary assessment 
(EMA) smartphone reports (i.e., Metricwire). The protocol, summarized graphically in Figure 1, includes a 1-week 
screening phase, 3-week intervention phase, and 3-month follow-up. Primary efficacy endpoints include 
endophenotypic markers of drinking outcomes used in clinical trials, i.e., craving elicited by alcohol cues and alcohol 
demand. Secondary efficacy endpoints are drinking outcomes. An exploratory aim relates biomarkers of immune 
activation and inflammation to behavioral endophenotypes of AUD and compares these in AALD/AUD patients 
versus those with AUD only.
7.B. Research Procedures and Materials.
7.B.1. General Procedures. 
The primary research site 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. All 
study procedures will be approved by the Brown University Institutional Review Board (IRB) prior to enrolling any 
human subjects in this research. Additionally, investigators will apply for an IRB authorization agreement (IAA) for 
Lifespan and submit a separate IRB application for the Providence VAMC, as these will be the primary recruitment 
sites for alcohol-associated liver disease patients, with recruitment (described below) including chart review and 
on-site screening. All aspects of this study protocol will be offered in English or Spanish, at the preference of the 
participant. 
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Screening. All interested volunteers who appear to be eligible based on an initial screening (described in 
Section 5. Recruitment Methods) will be invited to the CADRE laboratory at 121 South Main Street, Providence, RI, 
for an in-person screening to confirm eligibility. The in-person screening will ideally be completed by the designated 
research staff within two weeks of the initial inquiry. Potential participants will be informed that they will receive free 
behavioral counseling and that their therapist would receive results of their laboratory tests and information on their 
self-reported feelings and drinking behaviors in daily life. After the study procedures are described in detail, 
participants will provide written informed consent. After obtaining written informed consent, participants will be asked 
to complete a locator form which details their contact information as well as the contact information of two friends 
or relatives who can be contacted for assistance in locating the participant. In-person screening processes will 
follow written informed consent, and all in-person screening data saved for research purposes will be safeguarded 
as described in Part VI. Data Security Assessment.
Intervention. All participants will receive psychotherapy utilizing manualized principles of motivational 
interviewing (MI) and cognitive-behavioral skill-building techniques, with an initial session (60min), two brief (10-
15min) check-ins at weeks 1 and 2, and a 30-min booster session at 3 weeks. Dr. Treloar Padovano (PI) is a 
licensed psychologist and has extensive experience delivering MI in the context of research and clinical practice. 
She will train and supervise postdoctoral interventionists in the specific study intervention. It is customary for brief 
interventions to include personalized drinking feedback. A research assistant will create a personalized feedback 
report including a summary of the participants’ self-reported drinking patterns, results of selected laboratory tests, 
and summary visual reports of drinking, craving, and negative affect from smartphone reports. Interventionists will 
use the feedback report to develop discrepancies between a goal of halting or reversing health risks versus 
continuing to consume alcohol. Participants will be given the option of in-person or telehealth sessions to allow for 
flexibility in the event that Brown University restricts laboratory access. The intervention will be offered in English or 
Spanish, at the preference of the participant. Sessions will be audio recorded for the purpose of coding treatment 
fidelity.
7.B.2. Research Materials Obtained from Human Subjects.
A key strength of this research project is the integration of research materials obtained from human subjects
via multiple data sources. These include (a) self-reported data collected by research staff via interviews and 
questionnaires, (b) self-reported data collected via a HIPAA-compliant smartphone application implemented in 
human subjects’ natural environments, stored on a HIPAA-compliant, cloud-based server, and monitored by 
research staff using a HIPAA-compliant web application (i.e., Metricwire), (c) biological specimens collected via 
research staff in our laboratory and processed either in house or at HIPAA-compliant local clinical laboratories (e.g., 
Eastside Clinical Laboratories or Quest), (d) breathalyzer readings, height, weight, blood pressure, and heart rate, 
all collected by research staff in our laboratory, and (e) human subjects’ performance on laboratory tasks assessing 
cognitive functioning. An additional strength of the research is the synergy with other CADRE projects, which is 
made possible through the implementation of a common set of core assessments. Measurement and data 
properties for behavioral markers and biomarkers specifically chosen to meet the project aims are listed in Tables 
1 and 2, respectively. Additional questionnaires included to test ancillary research questions specific to this research 
project are included in the attached data collection materials. Additional measures that are included in all CADRE 
projects are listed and described in the attached data collection materials. 
Table 1. Behavioral Markers:  Measurement and Data Properties
Behavioral markers
Abbrev.
Source
Measure
Scale
Primary Endpoints
Ecological Momentary Assessment
EMA
Alcohol craving
AC-EMA
App
Self-report
Continuous
Negative affect (PANAS-X guilt, sadness subscales)
NA
App
Self-report
Continuous
Morning report of yesterday’s total standard drinks
MRSD
App
Self-report
Count
Human Laboratory 
CRP
Alcohol craving (In Vivo Cue Reactivity Paradigm)
AC-HLAB
VAS
Self-report
Continuous
Heart rate (In Vivo Cue Reactivity Paradigm)
HR
Print-out
Criticare
system
Continuous
Blood pressure (In Vivo Cue Reactivity Paradigm)
BP
Print-out
Criticare 
system
Continuous
Alcohol demand (Alcohol Purchase Task)
APT
Paper
Self-report
Continuous
Secondary Endpoints
Percent days abstinent per week
PDA
TLFB
Interview
Continuous
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7.B.3. Laboratory Measures and Procedures.
Self-reported Alcohol Use and Disorder Status. Drinking patterns will be assessed at in-person 
screening and updated at all timepoints using timeline followback (TLFB) methodology1,2. Screening timeline will 
include the past 90 days and be updated at the baseline session and weekly visits. The 3-month follow-up timeline 
will also be for 90 days. The Mini-International Neuropsychiatric Interview (M.I.N.I.; paper version 7.0.2) is a brief, 
15-min, structured diagnostic interview that will be used to confirm eligibility3. Items of the Alcohol Use Disorder 
module will be asked at in-person screening and repeated at baseline, 3-week, and 3-month timepoints. The full 
MINI is part of the CADRE core battery (see attached data collection materials) and will be used to rule-out 
psychiatric exclusions. Procedures for suicidality and mental health monitoring are described in Appendix F. Breath 
alcohol concentrations (BrAC) will be assessed with an Alcoholsensor IV instrument (Intoximeters, Inc., St. Louis, 
MO) prior to participants signing informed consent and at the start of all study visits.
 Biomarkers. Direct and indirect biomarkers of drinking and AALD will be used to confirm drinking status 
and eligibility4. Direct, objective biomarkers of alcohol use include ethanol (EtOH) and metabolite levels in blood, 
breath, and urine samples. EtOH and metabolite levels are the most sensitive and specific biomarkers of alcohol 
intake, but reflect only very recent use. Phosphatidylethanol (PEth) is an abnormal phospholipid nonoxidative 
metabolite generated only in the presence of EtOH5,6. PEth is detectible for a period of 2-3 wks and can be detected 
up to >2 wks, maybe to 6 wks7. PEth has been validated in AALD patients with higher sensitivity/specificity8,9. 
Indirect markers, such liver enzymes including alanine transaminase (ALT), aspartate transaminase (AST), and γ-
glutamyl transferase (GGT), are used to detect chronic, heavy drinking. Immunologic biomarkers are summarized 
in Table 2. Biospecimens listed in Table 2 will be collected by our CADRE nurse practitioner at screening and all 
Percent heavy drinking days per weeka
PHDD
TLFB
Interview
Continuous
Standard drinks per heavy drinking day
DPHDD
TLFB
Interview
Count
Note. Abbrev.= Abbreviation; App = Smartphone application; LP-MC = Liquid chromatography – Mass spectrometry; ELISA = 
Enzyme-linked immunosorbent assay; VAS = Visual Analogue Scale; TLFB = Timeline follow-back.
a A heavy drinking day is defined as 4 or more drinks for women or 5 or more drinks for men.
Table 2. Biomarkers:  Measurement and Data Properties
Biomarkers
Abbrev.
Source
Measure
Scale
Direct Markers of Alcohol Consumption
Ethanol
EtOH
Breath
Breathalyzer
Continuous
Ethyl glucuronide
EtG
Urine
Urinalysis
Continuous
Phosphatidylethanol 
PEth
Plasma
LC-MS
Continuous
Diagnostic markers used for screening
Alanine transaminase
ALT
Serum
Clinical Lab
Continuous
Aspartate transaminase 
AST
Serum
Clinical Lab
Continuous
γ-glutamyl transferase 
GGT
Serum
Clinical Lab
Continuous
Platelet count (from clinical blood chemistry)
CBC
Serum
Clinical Lab
Count
Creatinine (to estimate glomerular filtration rate)
GFR
Serum
Clinical Lab
Continuous
Markers of Inflammation
Lipopolysaccharide
LPS
Plasma
ELISA
Continuous
LPS binding protein
LBP
Plasma
ELISA
Continuous
Brain-Derived Neurotrophic Factor
BDNF
Plasma
ELISA
Continuous
Interleukin-6
IL-6 
Plasma
ELISA
Continuous
Interleukin-10
IL-10 
Plasma
ELISA
Continuous
Interleukin-17A
IL-17A
Plasma
ELISA
Continuous
Interferon gamma
IFN-γ
Plasma
ELISA
Continuous
Tumor necrosis factor alpha
TNF-α
Plasma
ELISA
Continuous
Monocyte chemoattractant protein 1
MCP-1
Plasma
ELISA
Continuous
Markers of Immune Activation
Soluble cluster of differentiation 14
sCD14
Plasma
ELISA
Continuous
Soluble cluster of differentiation 163
sCD163
Plasma
ELISA
Continuous
Note. Abbrev.= Abbreviation; App = Smartphone application; LP-MC = Liquid chromatography – Mass spectrometry; ELISA = 
Enzyme-linked immunosorbent assay; VAS = Visual Analogue Scale; TLFB = Timeline follow-back.
a A heavy drinking day is defined as 4 or more drinks for women or 5 or more drinks for men.
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study visits. EtG will be tested on site. Blood vials will be placed in a cooler with an icepack for pickup by a courier 
from a local clinical laboratory who will analyze samples and upload results to an online web portal within 24 hrs. 
Inflammatory markers listed in Table 2 will be collected at all visits except screening and stored in a -80C freezer 
prior to immunoassays using Ella™.
In Vivo Cue-Elicited Craving Paradigm. Participants will be exposed to alcohol and water cues in the 
human laboratory via our in vivo cue reactivity paradigm. The participant's preferred alcoholic beverage is used as 
the in vivo alcohol cue. The procedure includes pouring the beverages into a glass in the presence of the participant. 
To standardize cue exposure, audio recordings will instruct participants to bring the glass to their nose and smell 
the beverage when high-pitched tones are presented and put the glass down and stop smelling the beverage when 
low-pitched tones are presented. Each cue exposure lasts approximately 90 seconds. An initial relaxation period is 
followed by exposure to the water cue, a second relaxation period, and finally two repeated exposures to the alcohol 
cue. This order is used to avoid carry-over effects of the alcohol cue. A visual analogue scale from 0 to 10 will 
assess craving, i.e., "How strong is your craving to drink alcohol right now?". Participants’ blood pressure and heart 
rate will be measured during the task via an automatic blood pressure cuff and finger heart rate monitor. A Criticare 
VitalCareTM 506N3 Series vital signs monitor with be used to obtain a printed record of blood pressure and heart 
rate measurements repeated every 3 minutes during the cue reactivity paradigm.
Alcohol Purchase Task. A 15-item APT will assess indices of alcohol demand as follows: intensity, 
breakpoint, Omax, Pmax, and elasticity. The instructional set will follow Jacobs and Bickel’s original procedure, modified 
to fit alcohol treatment rather than drug treatment13. A recent met-analysis supported the validity of the APT alcohol 
demand indices in light and heavy drinkers14.
Qualitative Exit Interview. A brief exit interview will be conducted at the Week-3 visit to provide information 
on feasibility and acceptability of the present research. The semi-structured interview will include questions about 
likes and dislikes of participating in the study, intervention, and smartphone application, as well as future plans for 
reducing or abstaining from alcohol and openness to additional assistance with reducing drinking. The interview will 
be audio recorded for the purpose of qualitative response coding. In addition to collecting this qualitative data, two 
questionnaire measures will provide a quantitative assessment of usability of the smartphone application (i.e., the 
10-item System Usability Scale) and satisfaction with the research project and intervention more broadly (i.e., the
8-item Client Satisfaction Questionnaire).
Use of the CADRE Clinical Laboratory Core. The CLC provides a core assessment battery to promote 
CADRE synergy and measure common mechanisms underlying chronic disease. Many of the biomarkers will 
overlap with other CADRE projects. Neuropsychological testing is included in the core assessment battery and will 
be repeated at week 3 and 3-month follow-up laboratory visits. While our primary aims focus on biobehavioral 
assessments, we will also consider socioeconomic and psychosocial influences. Socioeconomic measures will 
include employment status and educational level, income, home ownership, and perceived neighborhood 
disadvantage. Psychosocial measures will include perceived stress, discrimination, and life satisfaction. The CLC 
core battery also includes additional psychosocial measures of pain, trauma, family history, medical history, 
behavioral dysregulation, physical activity, sleep, and health-related quality of life. Additionally, drug toxicology, 
pregnancy testing, vital signs, and height/weight will be assessed at baseline. Please see the attached data 
collection materials for a list and description of CLC core assessments.
7.B.4. Natural Environment Measures and Procedures.
Ecological Momentary Assessment (EMA). EMA is a method for collecting self-monitoring data using 
smartphones. We will use EMA during a 1-week screening phase and 3-week intervention phase. Dr. Treloar 
Padovano has expertise in complex EMA sampling schemes to assess mechanistic components of substance 
misuse15,16,25–34,17,35,36,18–24. Participants may use their own smartphone or have one provided to them, with data 
transmitted wirelessly to the vendor’s HIPAA-compliant server. The sampling strategy will be relatively minimal to 
maximize compliance and ensure valid data. 

Morning reports will be the primary assessment of drinking, cannabis, nicotine, and other substance use
the previous day and will query quantity and type of alcohol and other substances consumed. Sleep quality
the prior night will also be assessed. Three morning-report questions will also assess meaning and purpose
in life as follows, “How meaningful does your life feel?”, “How much do you feel your life has purpose?”,
and “Are you searching for meaning in your life?”, with responses recorded on a sliding scale from 0 to 10.
Participants will indicate the amount of physical pain and pain interference they felt yesterday with two items
rated on sliding scales from 0 to 10. Four items will relate to yesterday’s drinking, i.e., “How intoxicated
were you from alcohol yesterday?” “How much did you enjoy drinking alcohol yesterday?” “How much did
you dislike drinking alcohol yesterday?” and “Did you drink more than planned yesterday?”, all rated on
sliding scales from 0 to 10. Next day drinking effects will be assessed with three items assessing hangover,
regret, and severity of alcohol problems, all rated on sliding scales from 0 to 10. A single text-entry item will
assess primary reason for drinking yesterday (for those who reported 1 or more alcoholic drinks) or primary
reason for not drinking yesterday (for those who reported 0 alcoholic drinks). Last, participants will be asked
to indicate the number of standard drinks of alcohol they plan to use that day. Importance and confidence
to avoid or limit drinking will be assessed with two items rated on sliding scales from 0 to 10. Last, plans to
use other substances will be assessed via a multiple checkbox item where they can check all that apply.
Importantly, responses to these questions will not be monitored in real time by study staff, and there will be
no mechanism for immediate intervention if a participant indicates substance-use plans.
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
Audible signals will prompt reports of craving, affect, and situational influences “right now”, with prompts 
delivered randomly in four, 3.5hr blocks stratified by time of day between 8am and 10pm. Participants will 
self-monitor and rate the intensity of their alcohol craving in daily life using a sliding scale from 0 to 10 via 
the question, “How strong is your craving to drink alcohol right now?”. Craving for cannabis and nicotine 
will also be assessed, i.e., “How strong is your craving to use cannabis right now?” and “How strong is your 
craving to use nicotine/tobacco right now?” Participants will also indicate recent drinking and other 
substance use, the presence of visible alcohol cues, situational factors (e.g., presence of others, presence 
of others drinking alcohol), and setting (e.g., home, public place). Participants will self-monitor and rate the 
intensity of their negative feelings in daily life, as assessed by items selected from the PANAS-X guilt and 
sadness subscales, i.e., guilty, angry at self, sad, and lonely37. In order to avoid priming negative feelings, 
these will be balanced with items from the joviality subscale: happy and energetic. Other feeling states will 
be assessed by the following: angry at others, hungry, tired, anxious, stressed, and irritable. All will be rated 
on sliding scales from 0 to 10. Physical pain will be rated with one item, “How intense is your physical pain 
right now?” on a sliding scale from 0 to 10.
8. Describe the compensation.   ☐ N/A
Click or tap here to enter text.
Total participant compensation will include in-person screening, baseline visit, progressively increasing payments 
for weekly visits, 3-month follow-up visit, initial telehealth session, booster session, and EMA daily payments and 
weekly bonuses. The duration of involvement (in minutes) and associated payment (in U.S. dollars) for each study 
component is as follows: in-person screening (75 min; $20), baseline visit (90 min; $50), Week 1 Visit (45 min; $40), 
Week 2 Visit (45 min; $45), Week 3 Visit (75 min; $50), 3-month follow-up visit (75 min; $60), EMA reports (up to 
10 total min per day; up to $4 per day for 28 days, total up to $112). EMA daily amounts and weekly bonuses are 
contingent on compliance with EMA protocols. Daily EMA amounts will be pro-rated based on compliance as 
follows: 80% or greater compliance = full $4 amount; 60% compliance = $3; 40% compliance = $2; $20% 
compliance = $1. EMA compliance rates of 80% or greater as a weekly average will incur a $20 bonus for that 
week. Frequent feedback regarding compliance will be provided to encourage reporting and be clear with 
participants about their expected compensation based on their compliance. Total compensation will be a maximum 
of $457 per participant for a total expected involvement of about 12 hours over 3.25 months. 
Participant compensation schedule.
Study component
Estimated time to 
complete (in minutes)
Compensation
Note.
In-person Screening
75
$20
Baseline Visit
90
$50
Week 1 Visit
45
$40
Week 2 Visit
45
$45
Week 3 Visit
75
$50
3-month Follow-up Visit
75
$60
EMA daily payments
~ 10 total min / day
$112
Up to $4 per day for 28 days.
EMA weekly bonuses
Not applicable
$80
Up to $20 per week for 4 
weeks.
Total Compensation:
$457
The method of compensation will be a reloadable debit card, i.e., ClinCard, managed through Greensphire, 
specialists in global clinical payment technologies, and MasterCard. It can be used wherever MasterCard is 
accepted. This system confers several improvements over a manual payment system in terms of enhanced 
efficiency, security, and confidentiality. The use of the system has been approved by Brown IRB for several existing 
projects. Compensation will be loaded onto the ClinCard on a weekly basis during the baseline and intervention 
phases (4 weekly compensation amounts). A final balance of compensation for the 3-month follow-up will be loaded 
onto the Clincard at that time as one final compensation amount. This method and amount of compensation is 
appropriate for the participant population age (18 years or older) and study activities based on time commitment 
and number of study visits. This method is used by other current CADRE projects at the Center for Alcohol and 
Addiction Studies (CAAS) and compensation is commensurate with other similar projects at CAAS.
Interested volunteers are compensated $20 for their time spent completing the in-person screening, 
regardless of whether they are enrolled. There is a $3.50 fee to acquire each Clincard and a load fee of $1.00 per 
load. For this reason, we will provide interested volunteers who are not eligible for the project a one-time $20 
Amazon gift card compensation amount rather than using the Clincard. The PI uses Amazon gift cards in other 
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Brown IRB-approved projects, and this process has worked well. Interested volunteers will be informed prior to in-
person screening that if they are not eligible for the project, they will be provided a one-time $20 Amazon gift card 
as compensation for their time. We may also provide a nominal ($1) gift to interested volunteers who complete an 
initial screening in a clinic, regardless of whether they enroll. 
Based on our prior research projects recruiting heavy drinkers for protocols with similar compensation and 
effort, we expect that approximately half of participants will require assistance with transportation to our laboratory. 
Bus passes or reimbursement for rideshare services will be offered. For those participants who prefer to drive 
themselves to our laboratory, we will provide covered parking a garage with free valet, when allowed per health 
safety regulations. 
9. Is the study a clinical trial?   ☒ Yes   ☐ No
10. Describe the possible research risks to participants.
Click or tap here to enter text.
10.A. Potential Risks.
Potential risks to human subjects participating in the proposed Research Project are minimal and as follows:
1.
Breach of Confidentiality.
2.
Psychological discomfort from answering questions about alcohol and other drug consumption patterns
and psychiatric symptoms.
3.
Physical risks associated with blood draw procedures including and not limited to pain or discomfort,
venipuncture, or fainting.
4.
Risk of coercion.
5.
Elevated alcohol craving in response to in vivo cue exposure.
10.B. Adequacy of Protection against Risks.
All procedures will be in accordance with 45 CFR Part 46 and will be approved by the Brown University Research
Protections Office IRB. Every effort will be made to protect participants from potential risks, and risks will be closely
monitored throughout the research project as described in the data safety and monitoring plan, Section 7. C.
10.B.1. Informed consent. Due to eligibility criteria listed above, in-person screening requires questions
about alcohol and drug use patterns and associated problems. Therefore, informed consent will be obtained at the 
start of the in-person screening session prior to engaging in any further activities. BrAC of .00g% will be confirmed 
when obtaining consent. The nature of the study will be described verbally and in writing via an informed consent 
document written to an 8th grade reading level in English or Spanish, depending on the interested volunteer’s 
preference. A brief quiz will be administered to assess comprehension of the procedures and risks described in the 
informed consent document. Interested volunteers will be informed that participation in research is entirely 
voluntary, and that they have the right to terminate study procedures at any time without risk of penalty. The names 
and office phone numbers of the project leader, Dr. Treloar Padovano, and on-site primary mentor, Dr. Monti, and 
research assistant will be provided on the consent document. Contact information for the Brown University IRB will 
also be provided on this document. Participants will be offered a signed copy of the consent document, and the 
original form will be kept in a locked filing cabinet.
10.B.2. Protections against Risk.
1.
Breach of Confidentiality. Multiple protections will be implemented to minimize risk of breach of
confidentiality as follows:
a.
Access to personally identifiable information collected in the proposed research project will be
strictly limited to Dr. Treloar Padovano and trained research staff.
b.
Personally identifiable information, i.e., name, phone number, and email address, will be obtained
initially for the purposes of screening and assigned a unique screening identification (ID) number.
c.
Information obtained during screening from interested volunteers who are ineligible for the study
will be stripped of all personally identifying information and retained only for providing meta-data
on research activities, e.g., number of screens completed, reasons for ineligibility, documenting
attempts to contact interested volunteers to schedule in-person screening visit.
d.
Once interested volunteers provide written informed consent to participate in the research project,
participant data and samples will be identified using a participant identification number (herein
referred to as “ID number”) that does not contain any personally identifiable information (e.g., the
number is not a birth date, social security number, or other identifying number).
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e.
All personally identifiable information will be kept in a separate location from the participant’s data. 
Hard-copy data containing personally identifying information, i.e., Locator Form and signed 
informed consent form, will be stored in a locked file cabinet drawer used solely for this purpose 
and accessible only to Dr. Treloar Padovano and trained research staff. 
f.
Links between personally identifiable information and the participant’s unique ID number will be 
kept in a separate location from the participant’s data in a password-protected file that is saved on 
a secure server maintained by Brown University Computing and Information Services (CIS).
g.
At the conclusion of the study, the file containing participant identifiers linked with unique participant 
IDs will be destroyed by Dr. Treloar Padovano. 
h.
The COBRE CLC Data Analyst and Data Systems Management Coordinator will ensure that digital 
data protection measures utilize the highest industry standards. 
i.
Data collected for this research project will be de-identified, password-protected, and stored in one 
of the two following manners: (1) HIPAA-compliant, cloud-based servers managed by outside 
vendors that are vetted and approved by Brown University CIS, with procedures approved by the 
Brown University IRB; (2) Brown University’s secure servers managed by our CIS department. 
j.
Biological samples collected in the course of the study will be marked with the participant ID number 
and will not be associated with personally identifiable information. Blood samples will either be (1) 
sent out for same-day processing by a local, HIPAA-compliant laboratory, or (2) stored in a freezer 
designated for this purpose in a locked room in the secure CAAS laboratory until transported to a 
local research laboratory for batch assays. 
2.
Psychological discomfort from answering questions about alcohol and other drug consumption patterns 
and psychiatric symptoms. All interviews and assessments will be conducted in a private room by 
trained research staff in a supportive manner, offering to explain to participants why certain questions 
are being asked. Research staff will be extensively trained in administering alcohol and other drug 
interviews in a manner that is nonresponsive and nonjudgmental, and they must pass this training and 
be approved by Dr. Treloar Padovano in order to administer these assessments. In addition, 
participants will be informed in writing and reminded through the protocol that they may withdraw from 
the study at any time without penalty or consequence. Participants who decide to withdraw from the study 
prior to completion will be paid for their participation up to that point.
3.
Physical risks associated with blood draw procedures including and not limited to pain or discomfort, 
venipuncture, or fainting. Blood collection has a risk of pain or discomfort and venipuncture. Precautions 
are taken to minimize this risk during blood collection. All blood collection is implemented by a licensed 
nurse practitioner who is a trained phlebotomist and has extensive medical training, thus minimizing 
risk of venipuncture. Risk of fainting is considered low and participants will be seated for all blood draws 
to minimize any potential for physical harm.
4.
Risk of coercion. The risk of coercion is low. The total amount of compensation during the study is 
modest given the study requirements and time commitment. All research staff will be specifically 
instructed in the need to avoid coercion. Participants will be assured that they are free to refrain from 
answering any questions or completing any tasks. Participants will be assured that participation in this 
research is strictly voluntary and that they may withdraw from the study at any time without penalty. 
Participants will be reminded of this at all phases of the study. 
5.
Elevated alcohol craving in response to in vivo cue exposure. The in vivo alcohol cue reactivity protocol 
is designed to experimentally induce short-term elevations in alcohol craving. Prior to ending each in-
person study session where the in vivo alcohol cue reactivity protocol is implemented, trained research 
staff will assess any residual elevations in craving. If the participant reports residual urge, Dr. Treloar 
Padovano or another trained clinician will speak with the participant and complete a structured protocol 
authored by study collaborator, Peter Monti, Ph.D., and published in Treating Alcohol Dependence: A 
Coping Skills Training Guide (Monti, et al., 2002). The protocol involves multiple components, including 
discussing reactions to the session, assessing urge, and, if necessary, talking down the urge prior to 
the participant leaving our laboratory.
11. Describe the anticipated benefits to participants. 
11.A. Potential Benefits of the Research to Human Subjects and Others. Participation in this research poses 
minimal risk, resulting in a favorable cost-benefit ratio. There are no demonstrated benefits to participants from 
participating in this study. Potential benefits, however, may include assistance with reducing harmful drinking 
patterns. Additionally, participants who express interest in receiving formal addictions treatment upon completion 
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of the study protocol will be offered the opportunity to speak with Dr. Treloar Padovano or another licensed clinical 
psychologist, who will review a list of local treatment options with the participant. Benefits to society are expected 
to stem from generation of new scientific knowledge informing our understanding of how reductions in alcohol use 
can reduce health risks, such as alcohol-related liver disease.
11.B. Importance of the Knowledge to be Gained. Harmful use of alcohol leads to multiorgan damage, injuries,
and cognitive-behavioral alterations causing 3 million deaths per year worldwide, and alcohol misuse is a leading
cause of preventable liver disease. This research project will contribute important scientific knowledge concerning
the intersection of biobehavioral markers of liver function, inflammation, and alcohol use. The research has the
potential to increase our understanding of the specific pathways by which excessive alcohol consumption
exacerbates the development of alcohol-associated liver disease. The risks to participants, which are considered
minimal, are reasonable in relation to the importance of the knowledge to be gained.
12. Does the study involve the use of secondary data (identifiable information or identifiable
biospecimens)?   ☐ Yes (complete Questions 12.1-12.3)   ☒ No (skip to Question 16)
12.1 Provide the source of the data.
Click or tap here to enter text.
12.2 Describe the type(s) of data / biospecimens and date range(s) of the data you will use and 
the characteristics of the study research population (e.g., age range, sex, and any other 
pertinent demographic information. 
Click or tap here to enter text.
12.3 Describe how will you use, study, or analyze the data / biospecimens.
Click or tap here to enter text.
13. Does the study involve the use of PHI from a HIPAA-covered entity?
☒Yes (complete Question 13.1-13.2)     ☒ No (proceed to Question 14)
If “yes,” please upload Appendix G: Use of Protected Health Information (PHI) in Research. If
applicable, upload a HIPAA Authorization form.
13.1 Describe how authorization to access the data will be obtained. 
The HIPAA Authorization Form and Medical Release Form are required to share protected health information 
from the medical record with the Brown University research study. This information is necessary to 
characterize patients who are recruited to the study. The HIPAA Authorization Form and Medical Release 
Form may be signed at any time but must be signed before protected health information from the medical 
record can shared with the Brown University Research Study.
13.2 Is the data considered a limited data set?      ☐ Yes
☒No
14. Does the study involve the use of Family Educational Rights and Privacy Act (FERPA) or 
Protection of Pupil Rights Amendment (PPRA) data? 
☐ Yes (complete 14.1-14.2)   ☒ No (proceed to Question 15)
14.1  What type of FERPA or PPRA data will be accessed for this research?
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☐Directory information
☐Education records
☐Instructional material
☐Personally identifiable information (PII)
☐Data involving a PPRA-protected category
☐Other, please describe: Click or tap here to enter text.
14.2  Describe how authorization to access the data will be obtained. 
Click or tap here to enter text.
15. Is a Data Use Agreement (DUA), Material Transfer Agreement (MTA), or other agreement
required by the source to obtain, use, study, or analyze the data / biospecimens?
☐Yes      ☒ No
If “yes,” please upload a copy of the Agreement(s) (draft or executed).
16. What type of data will be collected? 
☒ Identifiable biospecimens
☒ Personally identifiable Information (PII)
☒ Coded data and the study team has access to the linking file / key
☐ Coded data and the study team does not have access to the linking file / key 
☐ Anonymous data
☐ Publicly available data
☒ Other, please describe: Metricwire is used to collect data via smartphone reports in daily life. 
This data type and procedures to maintain the confidentiality of participant data are described below.
17. Briefly describe your plan for managing the integrity of the data and monitoring the safety of
participants.    ☐ N/A
Identifiers. Data and biospecimens collected for this project will be deidentified, meaning that identifiers will
be stored separately from study data and biospecimens. Research staff will maintain a password-protected
file that contains links of personal identifiers with unique participant identification (ID) numbers. This file will be
stored on our secure departmental server that is managed by Brown CIS. This file will be kept for the duration
of the study and will be destroyed at the conclusion of the study by the PI. Justification. This is a study of
biobehavioral mechanisms of addiction and chronic disease and requires biospecimen collection for screening
eligibility and addressing the project aims. Identifiers are needed because the study involves multiple
sessions. Proposed use. Identifiable contact information will be used to schedule laboratory visits and follow-
ups. Audio recordings can be used to code fidelity of postdoctoral interventionists to the manualized treatment
and evaluate treatment process. Audio recordings. Audio recordings will be collected via Zoom
videoconferencing software ONLY for the counseling sessions with postdoctoral interventionists. At the
conclusion of the Zoom counseling session, the Zoom audio file will be saved using the participant’s ID
number on our secure server immediately after each session and deleted immediately after each session from
Zoom. Audio recordings can be used to code fidelity to the manualized intervention and evaluate treatment
process. Additional audio recordings will be collected via a handheld audio recorder for the qualitative exit
interview completed by research staff at the Week 3 visit. Research staff will remind the participant of their
consent to be audio recorded and ask permission to proceed prior to turning on the handheld audio recorder.
The audio recorder saves files in an internal storage system. As soon as the session ends, research staff will
upload the audio files to our secure server with only the participant’s ID number. The original copy will be
immediately deleted from the audio recorder. Paper records. Paper project data collection forms will include
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locator forms so that participants can be contacted by study staff, project forms used by study staff to record 
information such as visit start and stop times, participant height and weight, etc., and project forms to record 
responses to interviews and questionnaires. Paper records will either include participant identifying 
information or participant ID numbers, but never both on the same paper record. Paper records containing 
participant identifying information will be stored separately from paper records identified by a participant ID 
number. The link for the paper records will be stored in a password-protected file on our secure departmental 
server and kept for the duration of the study and destroyed upon completion of the study. Filemaker. 
Filemaker is used to track subject enrollment and progress through the study protocol.  Subjects are identified 
only by a subject ID #, which is assigned sequentially and contains no PHI.  Scheduling of study visits as well 
as visit status is logged into Filemaker.  Filemaker is also used for reporting of target and study completion 
totals.  Users to the database are restricted based on project permissions, and login with username and 
password. The Filemaker database lives on a secure departmental server maintained by Brown CIS. 
Metricwire. When participants submit response data using the Metricwire Mobile App or sensor data is passively 
logged and the mobile device is connected to the internet, data are immediately synced to HIPAA-Compliant servers 
located in the United States and removed from the participant’s mobile device. The data are encrypted end-to-end during 
transmission using TLS (1.2 &1.3) Protocol. Metricwire servers use an Encryption Token to verify that the data is 
coming from the correct source (authenticity) and that the data have not been modified in-transit (integrity).  If an 
internet connection is not available, the data are temporarily stored on the participant’s mobile device. The Metricwire 
Mobile Application stores response and sensor data in an encrypted format without any additional identifying 
information using AES-256 encryption keys. The data cannot be accessed using the Mobile Application Interfaces. When 
the Metricwire Mobile Application detects an internet connection, encrypted data are securely transmitted to Metricwire 
servers and removed from the device. App data are encrypted using AES 256 encryption. The Metricwire app can access 
only basic device features, such as OS Type & Version; Connectivity (Wifi vs Cell Network); App Permissions 
(Notifications, Location, etc); Battery Level, Charging & Disk Space; Localization Settings (Country/Language) 
18. How will you protect the privacy of participants? 
Access to private identifiable information collected in this study will be strictly limited to the PI and primary 
research staff. Participant data ad biospecimens will be identified using a unique participant ID number that 
is not related to personal identifiers. .
19. Does the study have or will you apply for a Certificate of Confidentiality (CoC)?
☒ Yes    ☐ No
20. How will you maintain the confidentiality of participant data? 
Links between personally identifiable information and participant IDs will be stored, secured, and destroyed 
upon completion of the study. Signed consent forms will be stored as described above and accessible only to 
the PI and trained research staff. 
21. Who will have access to your identifiable study data / biospecimens? 
☒ Brown PI and other Brown research team members (including advisor). 
Describe how unauthorized access by others will be prevented.
Data will be stored in deidentified files on our secure departmental server that is managed by Brown CIS. 
The COBRE Clinical Lab Core data systems management coordinator and data analyst will ensure that 
digital data protection measures utilize the highest industry standards. Biological specimens collected in 
the course of the study will be marked with the participant’s ID. Blood samples that are not sent to local 
HIPAA-compliant clinical laboratory for immediate analysis will be stored in a freezer in a protected lab 
space at 121 South Main Street or Brown-hosted biorepository.
☐ Data will be shared with research collaborators external to Brown. 
Describe how you will securely share / transfer the data outside of Brown.
Click or tap here to enter text.
☐Data will be shared with a data repository.
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Describe how you will securely share / transfer the data outside of Brown.
Click or tap here to enter text.
PRINCIPAL INVESTIGATOR AGREEMENTS & RESPONSIBILITIES 
 A. Conduct of the Research
1. I accept responsibility for the ethical conduct of this research and protection of participants as set 
forth in the Belmont Report and all applicable federal and state regulations and requirements 
pertaining to human subjects research, including but not limited to the Department of Health and 
Human Services’ Protection of Human Subjects (45 CFR 46), and the Food and Drug 
Administration’s Protection of Human Subjects (21 CFR 50) and Institutional Review Boards 
(21 CFR 56).
2. I accept responsibility for ensuring that all members of the research team comply with all Brown 
policies and procedures pertaining to human subjects research. 
3. I accept responsibility for ensuring that all members of the research team have or will complete 
the appropriate education and training to protect participants before any work begins with 
participants or identifiable information / biospecimens.
B. Ensuring and Maintaining Compliance
1. I will comply with relevant regulatory and institutional reporting requirements, including Brown 
University’s Reportable Events Policy. 
2. I will notify the Brown HRPP when I have completed all activities involving human subjects or 
identifiable participant information or identifiable biospecimens.
3. I will maintain approval, as applicable, with collaborative parties, including approvals from other 
countries or jurisdictions.
4. I will cooperate with any post-approval monitoring or auditing of study activities and/or study 
records as requested and/or required by the Brown ORI, the Brown IRB, funding entities, 
sponsors, and/or any federal or state regulatory agencies.
C. Study records, Reports and Documentation
1. I will comply by Brown’s Research Data and Research Materials Management, Sharing and 
Retention Policy.
2. I will maintain all research protocol materials and consent materials for the duration of this 
study.
3. I will maintain research records for at least three years following the end of this research, or for a 
longer length of time if specified in applicable regulations or sponsor requirements. I will take 
measures to prevent accidental or premature destruction of these records.
               
By submitting this document, I certify that I have read and agree to uphold all of 
the Agreements and Responsibilities in this application.
Brown University IRB Approval Nov 24 2020