A Photoplethysmography Sensor-based Personalized Feedback Intervention for Heavy-drinking Young Adults Targeting Heart Rate Variability, Resting Heart Rate, and Sleep
Phase: NA
Conditions: Heavy Drinking, Harmful; Use, Alcohol
Sponsor: Yale University

APPROVED BY THE YALE UNIVERSITY IRB 11/11/2022
CLINICAL STUDY PROTOCOL
Observational Study of Individual or Group Template
A photoplethysmography sensor-based personalized 
feedback intervention for heavy-drinking young adults 
targeting heart rate variability, resting heart rate, and sleep
 Protocol Number
2000030417  
Protocol Version
11/8/2022
Version 4
Confidentiality Statement:
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Protocol Number 2000030417
1/20/2022Version 3
2
 
Synopsis
Purpose 
Heavy alcohol use among young adults is an important public health problem. 
Alcohol use disorder (AUD) onset peaks during young adulthood (i.e., 18-25).[1] 
Young adults report the highest rates of heavy drinking,[2] which puts them at 
increased risk for substantial negative consequences such as accidental injury, (i.e., 
the primary cause of death in this group),[3-5] and makes them a priority population for 
intervention. 
Current alcohol prevention and early intervention efforts for young adults have 
limitations. Effective alcohol interventions are available for young adults but tend to 
have small effects on drinking.[6-8] Most young adults do not seek help for their 
drinking, often due to low perceived need.[9-12] Moreover, young adults are least 
likely to have medical visits with a healthcare provider[13, 14] where they could 
receive effective alcohol preventive services.[15] There are also gaps in access. While 
college students tend to have more support services, particularly free and/or low cost 
options, their non-college same aged peers do not. [16]
    Effective strategies need to better align with young adults’ health practices and 
preferences. Though alcohol help-seeking may be low among young adults, they are 
open to receiving help for other health behaviors such as sleep and exercise. [17-19] 
These health topics may provide alternative gateways for intervening on alcohol use, 
bypassing the need for self-identification. Young adults, a generation that grew up with 
the convenience of technology, are also increasingly turning to mobile and digital 
health tools. [20-22]
Mobile health interventions that embed brief alcohol intervention content may offer 
a novel solution. We developed and conducted a preliminary test of a mobile sleep 
intervention for heavy-drinking young adults for engaging them in treatment and 
reducing their drinking (see Preliminary Studies).[19] We targeted sleep because poor 
sleep is common among heavy-drinking young adults [23, 24] and an AUD risk factor, 
[25-31] young adults are interested in their sleep health, [32] and sleep interventions 
address alcohol use as standard care, thereby providing a practical opportunity to 
embed alcohol content. Within the last decade, there has also been an explosion in 
the importance of sleep [33-35] and technology options for improving it.  [36, 37] 
Qualitative data from this pilot (N=42) and our ongoing R34-funded follow-up study 
(96/120 enrolled to date) generated new hypotheses. Specifically, subjects expressed 
an interest in receiving feedback about other health outcomes besides sleep and 
indicated that feedback showing the negative effects of alcohol and/or sleep on health 
biomarkers would further motivate them to change their behavior. 
New sensor technology, that measures heart rate variability, a non-invasive, 
robust biomarker of health, shows potential for alcohol prevention and early 
intervention. In addition to sleep, there has been a rapid increase in the importance of 
heart rate variability (HRV) as a useful biomarker for tracking health and well-being, 
due in large part to new photoplethysmography (PPG) sensors and mobile apps that 
capture HRV, resting heart rate (RHR), and sleep. [38] HRV reflects cardiac control of 
the autonomic nervous system (ANS). [38] Greater HRV indicates a more resilient 
biological system that flexibly adjusts to changing demands and accordingly, is related 
to better physical and mental health. [39-43] Acute alcohol use reduces HRV; 
individuals with AUD have lower HRV than controls; [44] and HRV may be lower 
among heavy-drinking young adults compared to their non- or moderate-drinking 
peers. [45] Poor sleep may also reduce HRV. [46] The results of preliminary studies 
suggest that biofeedback interventions to improve HRV (i.e., paced breathing 
protocols) may reduce alcohol craving among individuals in substance use treatment 
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Protocol Number 2000030417
1/20/2022Version 3
3
or recovery programs. [47] HRV biofeedback may also have potential as an alcohol 
prevention/early intervention strategy, particularly receiving feedback about alcohol 
effects on HRV. This hypothesis has not been tested but users of this new PPG 
sensor technology reported reductions in drinking after observing negative effects of 
alcohol use on their health data. [48] PPG sensors and integrated mobile apps 
analyze user health and behavior data and can tailor health advice to these data, 
thereby creating a unique alcohol intervention opportunity. Thus, a controlled test of 
HRV/RHR/sleep monitoring and feedback on drinking via this new PPG technology 
warrants further study.
We will conduct the first controlled test of a personalized feedback intervention 
targeting HRV, RHR, and sleep for heavy-drinking young adults via PPG sensors and 
electronic daily diaries to provide preliminary data for a larger grant application. The 
study is directly responsive to NIAAA strategic directions focused on novel alcohol 
prevention and intervention efforts for young people. This innovative strategy could 
have great potential as it does not rely on self-identification for alcohol treatment, [9-
12] targets important substance use risk factors (i.e., sleep, HRV), [25-31, 44, 47] is 
applicable for all young adults, is easily accessible, and uses technology, which 
appeals to young adults. [20-22] 
We expect that a feedback intervention targeting HRV, RHR, sleep and their 
association with alcohol use will reduce drinking in young adults. The study will yield 
preliminary data for a larger, definitive study. The rich database will allow for an 
exploration of the links among these health variables to inform our understanding of 
their role in young adult AUD risk.
Primary Objective
We propose to conduct the first controlled test of a feedback intervention targeting heart 
rate variability (HRV), resting heart rate (RHR), and sleep, for heavy-drinking young adults 
(18-25) and will leverage the capabilities of a consumer-marketed PPG sensor/mobile 
app, OURATM. We will evaluate the feasibility, acceptability, and preliminary efficacy of 
this intervention for promoting improvements in drinking.
Primary Aim 1: To examine the preliminary efficacy of a PPG-sensor based HRV, 
RHR, sleep feedback intervention on alcohol outcomes measured using validated 
assessments (Timeline Followback Interview (TLFB)[  & PROMIS™) and diary data.
Hypothesis: The Feedback group will report fewer total drinks consumed compared to the 
Assessment group. We will also examine secondary drinking outcomes: drinks per 
drinking day, % heavy drinking and abstinent days, alcohol-related consequences, and 
daily diary entries of alcohol use before bedtime.
Secondary Objective
We will evaluate the preliminary efficacy of this intervention for promoting improvements 
in sleep and health as secondary outcomes.
Aim 2.1: Examine condition effects on PROMIS™ sleep quality and sleep-
related impairment self-ratings, controlling for baseline, using mixed effects 
models. Hypothesis: The Feedback group will have better self-reported PROMIS™ 
sleep quality ratings compared to the Assessment group. We will also examine 
secondary sleep outcomes: PROMIS™ sleep-related impairment ratings, sensor-
derived quantitative sleep outcomes (i.e., duration, efficiency, awakenings, % of time 
in sleep stages, bed/wake times), and daily diary ratings of sleep quality.
Aim 2.2: To examine the preliminary efficacy of a PPG-sensor based HRV, RHR, 
sleep feedback intervention on HRV measured using sensor data. Hypothesis: 
The Feedback group will report greater HRV compared to the Assessment group. We 
will also examine RHR as a secondary outcome.
Third Objective
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Protocol Number 2000030417
1/20/2022Version 3
4
Aim 2.3: To evaluate intervention feasibility and acceptability using subject post-
treatment ratings and interviews and use metrics. Hypothesis: Feedback will rate 
higher than Assessment.
Study Design
The purpose of this study is to test a mobile health intervention for young adults who 
report heavy alcohol use. The health intervention includes: (1) alcohol use and other 
health self-monitoring including use of a wearable biosensor, (2) a mobile application, and 
(3) personalized feedback and tailored health tips about your health and alcohol use data.
This study is the first controlled test of an HRV/RHR/sleep feedback intervention for 
heavy-drinking young adults (N=60; ages 18-25) and will take advantage of a marketed 
PPG sensor and mobile app, OURATM. Subjects will be randomly assigned to 1 of 2 
conditions: (1) Assessment (n=30) or (2) Feedback (n=30). The Assessment group will 
not have access to the OURA™ mobile app and will not receive any health feedback. The 
Feedback group will have access to the OURA™ app and will receive feedback. The 
OURA™ app provides daily summaries of HRV, RHR, and sleep that subjects can view 
on the app. In addition, every 2 weeks, we will send a written report via text/email that: (1) 
summarizes subjects’ alcohol use and the links with their HRV/RHR/sleep data and (2) 
provides health advice tailored to this data. 
Following intake, all subjects will wear the OURATM daily for 6 weeks and will complete 
daily electronic diaries of alcohol use and sleep. All subjects will then complete follow-ups 
at Weeks 6 and 10. We will use standardized assessments to measure alcohol 
consumption and consequences (TLFB, PROMIS™)[56, 57] and self-reported sleep 
outcomes (PROMIS™).[58] The OURA™ will measure quantitative sleep outcomes, HRV, 
and RHR. Daily electronic diaries will measure sleep quality and alcohol use. The primary 
alcohol outcome will be TLFB total drinks consumed, a composite measure of drinking 
quantity/frequency sensitive to change in our young adult research [19] and other brief 
alcohol interventions for this population. [6, 7, 51] Secondary alcohol outcomes will 
examine other effects on drinking: TLFB % heavy drinking and abstinent days; drinks per 
drinking day; PROMIS™ alcohol-related consequences; and daily diary entries of alcohol 
use before bedtime. The primary sleep outcome will be PROMIS™ sleep quality ratings, 
sensitive to change in our young adult research. [19] Secondary sleep outcomes will 
include PROMIS™ sleep-related impairment ratings, OURA™ quantitative sleep 
outcomes (i.e., duration, efficiency, latency, wakefulness, % time in sleep stages, 
bed/wake times) and sleep quality daily diary entries. The primary health outcome will be 
OURA™ HRV due to its strong association with heavy drinking. [43, 44] OURA™ RHR 
will be a secondary outcome. We will evaluate feasibility and acceptability with treatment-
exit interviews and OURA™ use metrics (below). 
Eligible subjects will be randomized to: (1) Assessment or (2) Feedback. All subjects will 
begin wearing an OURA™ right after intake and will complete daily diary assessments. 
Assessment (A) (n=30): Subjects in this group will only monitor their health/behaviors 
and will not receive any health feedback or advice. They will wear the OURA™ daily and 
complete daily electronic diaries about bedtime behaviors (e.g., amount/timing of alcohol 
use) and their sleep for 6 weeks. Diaries will be programmed in MEI Research  and sent 
via text message each morning, a successful procedure for our current R34-funded study. 
Feedback (F) (n=30): Subjects in this group will monitor their health/behaviors and will 
receive health feedback and advice. Subjects will wear the OURA™ daily and complete 
daily MEI Research diaries for 6 weeks. They will also have access to the OURA™ mobile 
app. Subjects will receive the following daily health information from the OURA™ app: (1) 
HRV, RHR, sleep (i.e., duration, efficiency, latency, sleep stages, timing, wakefulness), 
body temperature, respiratory rate, and physical activity (i.e., steps, calories burned); (2) 
composite scores from 0-100 (≥85 optimal) for “Sleep”, “Activity”, and “Readiness” (i.e., 
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Protocol Number 2000030417
1/20/2022Version 3
5
overall measure of recovery, based on HRV, that signals capacity to perform at physical, 
mental, cognitive best); and (3) advice regarding optimal bedtime, activity progress, 
inactivity, and recovery. At intake, we will orient subjects to OURA™ app health feedback 
and advice. At Weeks 2, 4, and 6, subjects will receive written reports sent via a text/email 
link that summarizes their alcohol use (e.g., drinks per week, # of heavy occasions, peak 
BAC) and the links between drinking and OURA™ health outcomes as well as tailored 
advice for improving health, including evidence-based brief content for alcohol (e.g., 
standard drinks, low risk drinking guidelines, BAC feedback, controlled drinking tips) [40-
42] and sleep (e.g., sleep hygiene, stimulus control). [19, 53, 54, 59, 60] We will derive 
these reports using the OURA™ Teams dashboard and daily diaries; subjects will not 
have dashboard access.
Study Date Range and Duration
Study procedures will include: an initial, in-person intake appointment (Week 0), a 6- week 
intervention phase, and 2 follow-up visits (Weeks 6 and 10). We anticipate that 
recruitment to follow-up will take 2 years.
Number of Study Sites 
Sites: Screening appointments will take place at the Connecticut Mental Health Center 
(CMHC) main campus or the Substance Abuse Treatment Unit, a satellite location of 
CMHC. The Yale School of Nursing Biobehavioral Laboratory is also available as a back-
up space for appointments. Follow-up visits will be conducted virtually using ZOOM.
Primary Outcome Variables
Standardized, consensus-based measures for assessing alcohol, sleep and 
other health outcomes were selected to assess primary and secondary aims. 
These measures are described below.
Timeline Follow-back Interview (TLFB): Valid/reliable/standardized interview to 
obtain alcohol quantity/frequency estimates [56] for a 30-day period prior to enrollment 
in the study and monthly following intake for a total of 3 months.(51) Calendar prompts 
and memory aids (e.g., holidays) are used to facilitate accurate recall of substance use 
during the targeted period. We will derive the following 30-day summary variables for: 
total drinks, drinks per drinking day, % heavy and abstinent days. 
PROMIS™ Alcohol Consequences: Valid/reliable measures of positive/negative 
alcohol consequences.[57]
Alcohol daily diaries: subjects will record the timing and amount of alcohol use before 
bedtime.[71]
Physical Fitness/Activity: Self-reported assessments with validity against objective 
measures. [74, 75]
Intervention Feasibility/Acceptability: OURATM use metrics; quantitative and 
qualitative ratings of OURATM and diary self-monitoring and health feedback/advice 
components using treatment evaluation surveys and exit interviews (e.g., ease of use, 
helpfulness, satisfaction, suggestions for improvement).
Secondary and Exploratory Outcome Variables (if applicable)
PROMIS™ Sleep-Related Impairment and Sleep Disturbance: Valid/reliable 
measures of perceived alertness, sleepiness, during waking hours and functional 
impairments due to sleep problems and perceived sleep quality/satisfaction and 
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Protocol Number 2000030417
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6
difficulty initiating/maintaining sleep.[58]
Sleep daily diaries: subjects will rate their sleep quality upon waking.[72]
PROMIS™ Positive Affect/Depression/Anxiety: Valid/reliable measures of well-
being, negative affect.[57, 73]
Physical Fitness/Activity: Self-reported assessments with validity against objective 
measures. [74, 75]
Intervention Feasibility/Acceptability: OURATM use metrics; quantitative and 
qualitative ratings of OURATM and diary self-monitoring and health feedback/advice 
components using treatment evaluation surveys and exit interviews (e.g., ease of use, 
helpfulness, satisfaction, suggestions for improvement).
Study Population
Participants are 18-25 years of age, reported ≥4 heavy drinking occasions in the last 4 
weeks, and have a personal smartphone available for use along with the wearable sensor 
provided in the study.
We will recruit heavy-drinking young adults (N=60; ages 18-25 years old) from the local 
community through online advertising/social media (e.g., Facebook, Instagram, Snapchat) 
and flyers and notices displayed around the local community and college campuses. 
Subjects will be randomly assigned to 1 of 2 conditions: (1) Assessment (n=30) or (2) 
Feedback (n=30). 
Urine Drug Toxicology: JANT Pharmaceuticals rapid urine drug test kit for opiates, 
cocaine, barbiturates, amphetamines, benzodiazepines, or phenylcyclidine. Positive tests 
are an exclusion criterion.
Breath Alcohol Concentrations (BAC): Subjects need to test negative on a handheld 
breathalyzer- an Alcohol-Sensor III (Intoximeter Inc., St. Louis, MO). Participants need to 
test negative to provide consent at intake and need to test <.04% at subsequent in-person 
treatment and assessment visits.
Number of Participants
Targeted for enrollment at Yale for this protocol: 60 subjects (Assessment group [n=30] 
and Feedback group [n=30]). This is a preliminary study, which if promising will lead to a 
larger trial of this intervention approach. Sample size estimates were based on enrolling a 
sufficient number of participants to determine the feasibility, acceptability, and preliminary 
efficacy of this PPG-sensor based feedback and brief advice intervention for reducing 
drinking among heavy-drinking young adults. This number is feasible to recruit for a 2-
year study. Moreover, for Phase 1 psychotherapy intervention studies, the minimum 
recommended sample size is 15-30 subjects per group.
Study Schedule
There are 3 expected visits: an initial, in-person intake appointment (Week 0), a 6- week 
intervention phase, and 2 follow-up visits (Weeks 6 and 10). 
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7
Protocol Revision History
Version 
Date
Summary of Substantial Changes
Version 2, 
4/21/2021
Accepted tracked changes, included description of http://www.clinicaltrials.gov, 
included Oncore usage for payment, clarified clinical interviews will be conducted 
by licensed experts to determine if participant meets any exclusion criteria, and 
clarified that consenting process will occur at either in person or remotely.
Version 3
1/20/2022
Accepted tracked changes, added/changed measures that participants will 
complete at intake, week 6, and week 10, and clarified how participants will 
be completing daily diaries 
Version 4
11/8/2022 
Accepted tracked changes and clarified that diary administration will occur 
through MEI Research, not Qualtrics. 
Include the IRB approved protocol version number and date for each revision of the protocol. All 
version history should remain in the table and never be deleted. The oldest IRB approved version of 
the protocol should be listed on the top row. The most recent IRB approved version should be listed 
on the bottom row.
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Statement of Compliance 
This document is a protocol for a human research study. The purpose of this protocol is to 
ensure that this study is to be conducted according to the Common Rule at 45CFR46 
(human subjects) and other applicable government regulations and Institutional research 
policies and procedures.
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Abbreviations
Abbreviation 
Explanation
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Protocol Number 2000030417
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Glossary of Terms
Glossary
Explanation
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Table of Contents
Preface....................................................................................................................................2
Synopsis ..................................................................................................................................3
Purpose................................................................................................................................3
Primary Objective.................................................................................................................3
Secondary Objective ............................................................................................................3
Study Design........................................................................................................................3
Study Date Range and Duration ..........................................................................................4
Number of Study Sites .........................................................................................................4
Primary Outcome Variables .................................................................................................4
Secondary and Exploratory Outcome Variables (if applicable)............................................4
Number of Participants.........................................................................................................5
Study Schedule ....................................................................................................................5
Protocol Revision History.....................................................................................................6
Statement of Compliance.........................................................................................................7
Abbreviations ...........................................................................................................................8
Glossary of Terms....................................................................................................................9
1
Background/Literature Review........................................................................................13
1.1
Background .............................................................................................................13
1.2
Prior Experience (if applicable)................................................................................13
2
Rationale/Significance ....................................................................................................14
2.1
Rationale and Study Significance............................................................................14
2.2
Purpose of Study/Potential Impact ..........................................................................14
2.3
Potential Risks and Benefits....................................................................................14
2.3.1
Potential Risks..................................................................................................14
2.3.2
Potential Benefits .............................................................................................15
3
Study Purpose and Objectives .......................................................................................15
3.1
Hypothesis...............................................................................................................15
3.2
Primary Objective ....................................................................................................15
3.3
Secondary Objective (if applicable).........................................................................15
4
Study Design ..................................................................................................................16
4.1.1
General Design Description .............................................................................16
4.1.2
Study Date Range and Duration ......................................................................16
4.1.3
Number of Study Sites .....................................................................................16
4.2
Outcome Variables..................................................................................................16
4.2.1
Primary Outcome Variables .............................................................................16
4.2.2
Secondary and Exploratory Outcome Variables (if applicable)........................16
4.3
Study Population .....................................................................................................16
4.3.1
Number of Participants.....................................................................................17
4.3.2
Eligibility Criteria/Vulnerable Populations.........................................................17
5
Study Methods/Procedures .........................................................................................18
5.1
Study Procedures....................................................................................................18
5.1.1
Data Collection.................................................................................................18
5.1.2
Adverse Events Definition and Reporting.........................................................18
5.2
Study Schedule .......................................................................................................18
5.3
Informed Consent....................................................................................................19
5.3.1
Screening (if applicable)...................................................................................19
5.3.2
Recruitment, Enrollment and Retention (if applicable).....................................19
5.3.3
Study Visits (is applicable) ...............................................................................19
5.4
Statistical Method ....................................................................................................20
5.4.1
Statistical Design..............................................................................................20
5.4.2
Sample Size Considerations ............................................................................20
5.4.3
Planned Analyses.............................................................................................20
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5.4.4
Analysis of Subject Characteristics (if applicable)............................................20
5.4.5
Interim Analysis (if applicable)..........................................................................20
5.4.6
Handling of Missing Data .................................................................................20
6
Trial Administration.........................................................................................................20
6.1
Ethical Considerations: Informed Consent/Assent and HIPAA Authorization .........21
6.2
 Institutional Review Board (IRB) Review................................................................22
6.3
Subject Confidentiality.............................................................................................22
6.4
Deviations/Unanticipated Problems.........................................................................23
6.5
Data Quality Assurance...........................................................................................25
6.6
Study Records.........................................................................................................25
6.7
Access to Source.....................................................................................................25
6.8
Data or Specimen Storage/Security ........................................................................25
6.9
Retention of Records...............................................................................................25
6.10
Study Monitoring......................................................................................................26
6.11
Study Modification ...................................................................................................26
6.12
Study Completion ....................................................................................................26
6.13
Funding Source .......................................................................................................26
6.14
Conflict of Interest Policy.........................................................................................26
6.15
Publication Plan.......................................................................................................27
Appendices ............................................................................................................................28
List of Tables..........................................................................................................................29
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1 Background/Literature Review
1.1
Background
Alcohol use disorder (AUD) onset peaks during young adulthood (i.e., 18-25).[1] 
Compared to older adults, young adults report more frequent and heavier alcohol 
consumption that is linked to substantial negative consequences including risk of 
accidental injury, the primary cause of death among young adults.[49] Current 
alcohol intervention strategies for young adults have modest effects [7, 50, 51]and 
young adults rarely self-identify for specialized alcohol treatment.[8, 52] Thus, more 
work is needed to identify effective alcohol interventions and novel treatment 
engagement strategies to reduce this substantial public health burden.
Effective alcohol interventions are available for young adults but tend to have small 
effects on drinking. [6-8] Most young adults do not seek help for their drinking, often 
due to low perceived need.[9-12] Moreover, young adults are least likely to have 
medical visits with a healthcare provider [13, 14] where they could receive effective 
alcohol preventive services. [15] There are also gaps in access. While college 
students tend to have more support services, particularly free and/or low-cost 
options, their non-college same aged peers do not. [16]
Though alcohol help-seeking may be low among young adults, they are open to 
receiving help for other health behaviors such as sleep and exercise. [17-19]These 
health topics may provide alternative gateways for intervening on alcohol use, 
bypassing the need for self-identification. Young adults, a generation that grew up 
with the convenience of technology, are also increasingly turning to mobile and digital 
health tools.[20-22]
We developed and conducted a preliminary test of a mobile sleep intervention for 
heavy-drinking young adults for engaging them in treatment and reducing their 
drinking (see Preliminary Studies). [19] We targeted sleep because poor sleep is 
common among heavy-drinking young adults [23, 24] and an AUD risk factor, [25, 26, 
28-31] young adults are interested in their sleep health, [32] and sleep interventions 
address alcohol use as standard care, thereby providing a practical opportunity to 
embed alcohol content. Within the last decade, there has also been an explosion in 
the importance of sleep [33-35] and technology options for improving it. [36, 37] 
Qualitative data from this pilot (N=42) and our ongoing R34-funded follow-up study 
(96/120 enrolled to date) generated new hypotheses. Specifically, subjects 
expressed an interest in receiving feedback about other health outcomes besides 
sleep and indicated that feedback showing the negative effects of alcohol and/or 
sleep on health biomarkers would further motivate them to change their behavior. 
In addition to sleep, there has been a rapid increase in the importance of heart rate 
variability (HRV) as a useful biomarker for tracking health and well-being, due in 
large part to new photoplethysmography (PPG) sensors and mobile apps that 
capture HRV, resting heart rate (RHR), and sleep. [38] HRV reflects cardiac control 
of the autonomic nervous system (ANS). [38] Greater HRV indicates a more resilient 
biological system that flexibly adjusts to changing demands and accordingly, is 
related to better physical and mental health. [39-43] Acute alcohol use reduces HRV; 
individuals with AUD have lower HRV than controls; [44] and HRV may be lower 
among heavy-drinking young adults compared to their non- or moderate-drinking 
peers. [45] Poor sleep may also reduce HRV.[46] The results of preliminary studies 
suggest that biofeedback interventions to improve HRV (i.e., paced breathing 
protocols) may reduce alcohol craving among individuals in substance use treatment 
or recovery programs. [47] HRV biofeedback may also have potential as an alcohol 
APPROVED BY THE YALE UNIVERSITY IRB 11/11/2022

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Protocol Number 2000030417
1/20/2022Version 3
14
prevention/early intervention strategy, particularly receiving feedback about alcohol 
effects on HRV. This hypothesis has not been tested but users of this new PPG 
sensor technology reported reductions in drinking after observing negative effects of 
alcohol use on their health data. [48] PPG sensors and integrated mobile apps 
analyze user health and behavior data and can tailor health advice to these data, 
thereby creating a unique alcohol intervention opportunity. Thus, a controlled test of 
HRV/RHR/sleep monitoring and feedback on drinking via this new PPG technology 
warrants further study.
We will conduct the first controlled test of a personalized feedback intervention 
targeting HRV, RHR, and sleep for heavy-drinking young adults via PPG sensors and 
electronic daily diaries to provide preliminary data for a larger grant application. The 
study is directly responsive to NIAAA strategic directions focused on novel alcohol 
prevention and intervention efforts for young people. This innovative strategy could 
have great potential as it does not rely on self-identification for alcohol treatment, [9-
12] targets important substance use risk factors (i.e., sleep, HRV), [25-31, 44, 47] is 
applicable for all young adults, is easily accessible, and uses technology, which 
appeals to young adults. [20-22]
1.2
Prior Experience (if applicable) 
Dr. Fucito and the research team has experience implementing and evaluating mobile 
behavioral interventions to help young adults with their alcohol use and sleep. This current 
study is a continuation of this line of work. In Dr. Fucito’s current R34 clinical trial [IRB 
Protocol # 2000021048], young adults expressed an interest in exit interviews to receive 
information about health biomarkers that are related to poor sleep and/or heavy alcohol use. 
For this purpose, we have opted to focus on the biomarkers of heart rate variability and 
resting heart rate.
Rationale/Significance
1.3
Rationale and Study Significance 

The study provides the first systematic, controlled test of a HRV, RHR, sleep 
monitoring and feedback intervention as a novel alcohol prevention/early intervention 
strategy in heavy-drinking young adults. Improving these other health targets at this 
developmental stage could have long-term payoffs such as reduced long-term AUD 
risk as well as improved long-term mental and physical outcomes. 

Use of a health promotion intervention to engage young adults to change their 
drinking is a paradigm shift.
Current young adult alcohol prevention/early intervention strategies largely rely on 
self-identification or identification by a healthcare provider. [6-8] Many young adults 
do not perceive a need for help with their drinking and are increasingly less likely to 
visit a healthcare provider. [13, 14]Thus, other “on ramps” to alcohol preventive 
services are urgently needed. Young adults are concerned about their health and 
sleep. [32] Therefore, for this population, it may be useful to embed alcohol-related 
content within a more comprehensive health program and connect alcohol use to 
other health outcomes.

As part of the intervention and as an objective outcome measure, the research 
incorporates new, validated sensor technology for continuously monitoring HRV, 
RHR, and sleep. We will use this data and alcohol and sleep diary data to deliver 
innovative feedback to young adults on the links between drinking and their health.

HRV, RHR, and sleep are non-invasive health biomarkers that are malleable. This is 
the first test of all 3
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biomarkers as a brief alcohol intervention for young adults. All 3 are important for 
physical and mental health [34, 35, 39-42] and can be improved with cost-effective, 
easily disseminated behavioral interventions. [47, 53-55]

Research on HRV biofeedback interventions for substance use is in its infancy. [47] 
To date, only a few,
small studies have tested biofeedback interventions to improve HRV as an adjunct to 
substance use treatment, none of these targeted sleep.[47] No studies have explored 
the value of HRV feedback for substance use prevention/early intervention or the 
potential benefit of simply monitoring HRV and providing feedback about the effects 
of substance use on HRV among young adults. 

This study tests an alcohol prevention/early intervention strategy that is applicable to 
the broad population of young adults (i.e., civilian, college, and military young adults). 
1.4
Purpose of Study/Potential Impact 
Heavy alcohol use among young adults is an important public health problem. Alcohol 
use disorder (AUD) onset peaks during young adulthood (i.e., 18-25).[1] Young adults 
report the highest rates of heavy drinking,[2] which puts them at increased risk for 
substantial negative consequences such as accidental injury, (i.e., the primary cause of 
death in this group),[3-5] and makes them a priority population for intervention. 
Current alcohol prevention and early intervention efforts for young adults have 
limitations. Effective alcohol interventions are available for young adults but tend to have 
small effects on drinking.[6-8] Most young adults do not seek help for their drinking, often 
due to low perceived need.[9-12] Moreover, young adults are least likely to have medical 
visits with a healthcare provider[13, 14] where they could receive effective alcohol 
preventive services.[15] There are also gaps in access. While college students tend to 
have more support services, particularly free and/or low cost options, their non-college 
same aged peers do not. [16]
    Effective strategies need to better align with young adults’ health practices and 
preferences. Though alcohol help-seeking may be low among young adults, they are 
open to receiving help for other health behaviors such as sleep and exercise. [17-19] 
These health topics may provide alternative gateways for intervening on alcohol use, 
bypassing the need for self-identification. Young adults, a generation that grew up with 
the convenience of technology, are also increasingly turning to mobile and digital health 
tools. [20-22]
Mobile health interventions that embed brief alcohol intervention content may offer a 
novel solution. We developed and conducted a preliminary test of a mobile sleep 
intervention for heavy-drinking young adults for engaging them in treatment and reducing 
their drinking (see Preliminary Studies).[19] We targeted sleep because poor sleep is 
common among heavy-drinking young adults [23, 24] and an AUD risk factor, [25-31] 
young adults are interested in their sleep health, [32] and sleep interventions address 
alcohol use as standard care, thereby providing a practical opportunity to embed alcohol 
content. Within the last decade, there has also been an explosion in the importance of 
sleep [33-35] and technology options for improving it.  [36, 37] Qualitative data from this 
pilot (N=42) and our ongoing R34-funded follow-up study (96/120 enrolled to date) 
generated new hypotheses. Specifically, subjects expressed an interest in receiving 
feedback about other health outcomes besides sleep and indicated that feedback 
showing the negative effects of alcohol and/or sleep on health biomarkers would further 
motivate them to change their behavior. 
New sensor technology, that measures heart rate variability, a non-invasive, robust 
biomarker of health, shows potential for alcohol prevention and early intervention. In 
addition to sleep, there has been a rapid increase in the importance of heart rate 
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variability (HRV) as a useful biomarker for tracking health and well-being, due in large 
part to new photoplethysmography (PPG) sensors and mobile apps that capture HRV, 
resting heart rate (RHR), and sleep. [38] HRV reflects cardiac control of the autonomic 
nervous system (ANS). [38] Greater HRV indicates a more resilient biological system that 
flexibly adjusts to changing demands and accordingly, is related to better physical and 
mental health. [39-43] Acute alcohol use reduces HRV; individuals with AUD have lower 
HRV than controls; [44] and HRV may be lower among heavy-drinking young adults 
compared to their non- or moderate-drinking peers. [45] Poor sleep may also reduce 
HRV. [46] The results of preliminary studies suggest that biofeedback interventions to 
improve HRV (i.e., paced breathing protocols) may reduce alcohol craving among 
individuals in substance use treatment or recovery programs. [47] HRV biofeedback may 
also have potential as an alcohol prevention/early intervention strategy, particularly 
receiving feedback about alcohol effects on HRV. This hypothesis has not been tested 
but users of this new PPG sensor technology reported reductions in drinking after 
observing negative effects of alcohol use on their health data. [48] PPG sensors and 
integrated mobile apps analyze user health and behavior data and can tailor health 
advice to these data, thereby creating a unique alcohol intervention opportunity. Thus, a 
controlled test of HRV/RHR/sleep monitoring and feedback on drinking via this new PPG 
technology warrants further study.
We will conduct the first controlled test of a personalized feedback intervention 
targeting HRV, RHR, and sleep for heavy-drinking young adults via PPG sensors and 
electronic daily diaries to provide preliminary data for a larger grant application. The 
study is directly responsive to NIAAA strategic directions focused on novel alcohol 
prevention and intervention efforts for young people. This innovative strategy could have 
great potential as it does not rely on self-identification for alcohol treatment, [9-12] 
targets important substance use risk factors (i.e., sleep, HRV), [25-31, 44, 47] is 
applicable for all young adults, is easily accessible, and uses technology, which appeals 
to young adults. [20-22] 
We expect that a feedback intervention targeting HRV, RHR, sleep and their association with 
alcohol use will reduce drinking in young adults. The study will yield preliminary data for a 
larger, definitive study. The rich database will allow for an exploration of the links among 
these health variables to inform our understanding of their role in young adult AUD risk.
1.5
Potential Risks and Benefits
1.5.1
Potential Risks 
The major potential risks in this study are related to intervention components, interviews/self-
report questionnaires, urine collection, and recording of treatment exit interviews.
Intervention Components:
PPG sensor use and mobile self-monitoring of alcohol use and health behaviors poses 
minimal risk. There are no side effects from wearing the OURA™ beyond minor inconvenience 
– users can shower and swim with the devices. OURA™ deidentifies user data and will 
distribute data to us using deidentified data via a password-protected dashboard that protects 
participants’ confidentiality. The brief health advice provided by the OURA™ mobile app and 
our personalized alcohol-related feedback and advice pose minimal risk. A great deal of this 
information is also available to young adults through external health websites. Our experience 
providing brief alcohol and health interventions to young adults and cognitive-behavioral sleep 
interventions indicates that they are well tolerated. Our research group has several PhD-level 
clinical psychologists available for consultation should the need arise. Participants will be 
monitored regularly through daily diaries and via remote reminders regarding study 
procedures. 
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The Oura ring is a wearable ring that includes multiple sensors to detect several health 
biomarkers including temperature, sleep, heart rate and connects to mobile application that 
provides users with information about their health status. Participants will wear the device 
and half will have access to the mobile application to view their health data so we can test 
the effect of using this device and receiving this health information on drinking behavior. The 
device is not FDA approved and it is our understanding that they are not seeking FDA 
approval status at this time for any medical indications. The Oura ring is intended for general 
health self-monitoring and is available to the public.
These will only be given to participants and tested by research staff. They will be stored in a 
locked cabinet in a locked research office at CMHC in between use. The devices will also be 
cleaned in between use by different participants.
Interviews and Self-Reports:
Research interviews and assessments, including completing daily health diaries, are all non-
invasive and should add no risk. The major disadvantage is the time it takes to complete 
them and possible breach of confidentiality. Our research group’s experience with these 
measures indicates that they are acceptable to participants. Dr. Fucito, a licensed clinical 
psychologist, will be available to meet with individuals and will provide staff with consultation 
should the need arise. Careful efforts aimed at maintaining confidentiality will be made, 
which are described below, and only participants’ study numbers will be recorded on the 
forms themselves in order to protect confidentiality.
Recording of Exit Interviews: Recording of interviews is necessary to evaluate participants’ 
reactions to self-monitoring activities (i.e., daily electronic diaries and the OURA™ smart ring) 
as well as personalized feedback and tailored health advice for those in the feedback group. To 
assure the confidentiality and protection of participants with respect to these procedures, the 
following steps will be taken:

Participants have the right to refuse recording. Participants who consent to recording will 
be informed that they have the right to stop recording at any time.

All recording will occur using ZOOM teleconferencing software, which is HIPAA-
compliant and password-protected. Only Dr. Fucito, Dr. Ash, or the Research 
Coordinator will record interviews.

Interviews will be saved on a password protected secure server. Digital file names will 
only be identified by participants’ study numbers. 

Access to digital recordings will be limited to key study personnel. 
Effective screening will exclude all participants who would be at greater risk for 
complications from the intervention and/or study participation because of medical or specific 
psychiatric illnesses. Dr. Fucito, a licensed clinical psychologist, will evaluate all potential 
participants for inclusion regarding their psychiatric suitability. If participants are not eligible 
for the study and/or request further assistance with alcohol use, physical health, and/or 
sleep once the study is completed, appropriate referrals will be provided. Upon study 
enrollment, numerous safeguards will be used to monitor participants. Participants will 
receive at a minimum, weekly contact from Study Staff for reminders about study 
procedures/address any logistical problems with diaries, sensors, or other procedures. Plus, 
all participants will wear a sensor and complete daily diaries. Sensor data and diaries can be 
monitored remotely. Dr. Fucito will be available to meet with participants and will provide 
participants with treatment referrals if they are interested.
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Right to privacy for participation in this research will be protected through alphanumeric 
coding of data (in place of names) and proper storage of research records, including 
treatment exit interviews. Collected materials will be maintained via an alphanumeric 
reference system maintained by Dr. Fucito. Participants’ names will appear only on the 
consent form, the HIPAA authorization form, and a master list maintained in a physically 
locked file that is separate from research data. Our data collection and management 
procedures are fully compliant with HIPAA. Access will be limited to personnel intimately 
involved in the study. A Certificate of Confidentiality will also be obtained from the National 
Institutes of Health to protect access to the records. However, participants will also be told 
that if they present with suicidal or homicidal ideation and/or report any form of child/elder 
abuse or report plans to damage property then we will have to report this to the appropriate 
authorities and/or provide them with referrals for immediate treatment. Electronic data will be 
de-identified, and password protected. Only members of the study team will have access to 
the physical or electronic data. OURA™ data are deidentified and are also protected through 
secure, password-protected servers. We will use an alphanumeric code to sign participants 
up to the OURA™ mobile app in place of their names.
1.5.2
Potential Benefits
All participants will engage in self-monitoring that may help participants learn more about 
their alcohol use, health, and/or sleep. In this study, half of the participants will receive 
personalized feedback about their health and behaviors as well as tailored, evidence-based 
advice, which may help them improve their drinking, health, and/or sleep. All participants will 
be provided compensation for their participation. They will be able to withdraw from the 
study at any time. There is a need to reduce heavy alcohol consumption and alcohol-related 
risks among young adults. The purpose of this study is to test a mobile health intervention 
for heavy-drinking young adults. Mobile interventions that target young adults’ other health 
concerns may provide alternative on ramps for intervening on alcohol use in this population. 
This study may help to engage more heavy-drinking young adults into treatment and reduce 
the substantial harms and healthcare costs associated with heavy alcohol use. 
2 Study Purpose and Objectives
2.1
Hypothesis
Hypothesis 1: The Feedback group will report fewer total drinks consumed compared to the 
Assessment group. We will also examine secondary drinking outcomes: drinks per drinking 
day, % heavy drinking and abstinent days, alcohol-related consequences, and daily diary 
entries of alcohol use before bedtime. 
Hypothesis 2: The Feedback group will have better self-reported PROMIS™ sleep 
quality ratings compared to the Assessment group. We will also examine secondary 
sleep outcomes: PROMIS™ sleep-related impairment ratings, sensor-derived 
quantitative sleep outcomes (i.e., duration, efficiency, awakenings, % of time in sleep 
stages, bed/wake times), and daily diary ratings of sleep quality
Hypothesis 3: The Feedback group will report greater HRV compared to the Assessment 
group. We will also examine RHR as a secondary outcome. 
Hypothesis 4: Feedback will rate higher than Assessment on measures of intervention post-
treatment ratings and interviews and use metrics.
2.2
Primary Objective 
Aim 1: Examine condition effects on total drinks consumed over Weeks 2-10 
(summarized over 4-week periods), controlling for baseline drinks. 
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2.3
Secondary Objective (if applicable)
 Aim 2.1: Examine condition effects on PROMIS™ sleep quality and sleep-related 
impairment self-ratings, controlling for baseline, using mixed effects models. 
Aim 2.2: To examine the preliminary efficacy of a PPG-sensor based HRV, RHR, sleep 
feedback intervention on HRV measured using sensor data. 
Aim 2.3: To evaluate intervention feasibility and acceptability using subject post-
treatment ratings and interviews and use metrics. 
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3 Study Design
3.1.1
General Design Description
Study Design
The purpose of this study is to test a mobile health intervention for young adults who report 
heavy alcohol use. The health intervention includes: (1) alcohol use and other health self-
monitoring including use of a wearable biosensor, (2) a mobile application, and (3) 
personalized feedback and tailored health tips about your health and alcohol use data.
This study is the first controlled test of an HRV/RHR/sleep feedback intervention for heavy-
drinking young adults (N=60; ages 18-25) and will take advantage of a marketed PPG 
sensor and mobile app, OURATM. Subjects will be randomly assigned to 1 of 2 conditions: 
(1) Assessment (n=30) or (2) Feedback (n=30). The Assessment group will not have access 
to the OURA™ mobile app and will not receive any health feedback. The Feedback group 
will have access to the OURA™ app and will receive feedback. The OURA™ app provides 
daily summaries of HRV, RHR, and sleep that subjects can view on the app. In addition, 
every 2 weeks, we will send a written report via text/email that: (1) summarizes subjects’ 
alcohol use and the links with their HRV/RHR/sleep data and (2) provides health advice 
tailored to this data. 
Following intake, all subjects will wear the OURATM daily for 6 weeks and will complete daily 
electronic diaries of alcohol use and sleep. All subjects will then complete follow-ups at 
Weeks 6 and 10. We will use standardized assessments to measure alcohol consumption 
and consequences (TLFB, PROMIS™)[56, 57] and self-reported sleep outcomes 
(PROMIS™).[58] The OURA™ will measure quantitative sleep outcomes, HRV, and RHR. 
Daily electronic diaries will measure sleep quality and alcohol use. The primary alcohol 
outcome will be TLFB total drinks consumed, a composite measure of drinking 
quantity/frequency sensitive to change in our young adult research [19] and other brief 
alcohol interventions for this population. [6, 7, 51] Secondary alcohol outcomes will examine 
other effects on drinking: TLFB % heavy drinking and abstinent days; drinks per drinking 
day; PROMIS™ alcohol-related consequences; and daily diary entries of alcohol use before 
bedtime. The primary sleep outcome will be PROMIS™ sleep quality ratings, sensitive to 
change in our young adult research. [19] Secondary sleep outcomes will include PROMIS™ 
sleep-related impairment ratings, OURA™ quantitative sleep outcomes (i.e., duration, 
efficiency, latency, wakefulness, % time in sleep stages, bed/wake times) and sleep quality 
daily diary entries. The primary health outcome will be OURA™ HRV due to its strong 
association with heavy drinking. [43, 44] OURA™ RHR will be a secondary outcome. We will 
evaluate feasibility and acceptability with treatment-exit interviews and OURA™ use metrics 
(below). 
Eligible subjects will be randomized to: (1) Assessment or (2) Feedback. All subjects will 
begin wearing an OURA™ right after intake and will complete daily diary assessments. 
Assessment (A) (n=30): Subjects in this group will only monitor their health/behaviors and 
will not receive any health feedback or advice. They will wear the OURA™ daily and 
complete daily electronic diaries about bedtime behaviors (e.g., amount/timing of alcohol 
use) and their sleep for 6 weeks. Diaries will be programmed in MEI Research and sent via a 
notification  each morning, a successful procedure for our current R34-funded study. 
Feedback (F) (n=30): Subjects in this group will monitor their health/behaviors and will 
receive health feedback and advice. Subjects will wear the OURA™ daily and complete daily 
MEI Research  diaries for 6 weeks. They will also have access to the OURA™ mobile app. 
Subjects will receive the following daily health information from the OURA™ app: (1) HRV, 
RHR, sleep (i.e., duration, efficiency, latency, sleep stages, timing, wakefulness), body 
temperature, respiratory rate, and physical activity (i.e., steps, calories burned); (2) 
composite scores from 0-100 (≥85 optimal) for “Sleep”, “Activity”, and “Readiness” (i.e., 
overall measure of recovery, based on HRV, that signals capacity to perform at physical, 
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mental, cognitive best); and (3) advice regarding optimal bedtime, activity progress, 
inactivity, and recovery. At intake, we will orient subjects to OURA™ app health feedback 
and advice. At Weeks 2, 4, and 6, subjects will receive written reports sent via a text/email 
link that summarizes their alcohol use (e.g., drinks per week, # of heavy occasions, peak 
BAC) and the links between drinking and OURA™ health outcomes as well as tailored 
advice for improving health, including evidence-based brief content for alcohol (e.g., 
standard drinks, low risk drinking guidelines, BAC feedback, controlled drinking tips) [40-42] 
and sleep (e.g., sleep hygiene, stimulus control). [19, 53, 54, 59, 60] We will derive these 
reports using the OURA™ Teams dashboard and daily diaries; subjects will not have 
dashboard access.
3.1.2
Study Date Range and Duration
Study procedures will include: an initial, in-person intake appointment (Week 0), a 6- week 
intervention phase, and 2 follow-up visits (Weeks 6 and 10).
3.1.3
Number of Study Sites
Sites: Screening appointments will take place at the Connecticut Mental Health Center 
(CMHC) main campus or the Substance Abuse Treatment Unit, a satellite location of CMHC. 
The Yale School of Nursing Biobehavioral Laboratory is also available as a back-up space 
for appointments. Follow-up visits will be conducted virtually using ZOOM.
3.2
Outcome Variables
3.2.1
Primary Outcome Variables
Timeline Follow-back Interview (TLFB): Valid/reliable/standardized interview to obtain 
alcohol quantity/frequency estimates [56]for a 30-day period prior to enrollment in the 
study and monthly following intake for a total of 3 months.(51) Calendar prompts and 
memory aids (e.g., holidays) are used to facilitate accurate recall of substance use during 
the targeted period. We will derive the following 30-day summary variables for: total 
drinks, drinks per drinking day, % heavy and abstinent days. 
PROMIS™ Alcohol Consequences: Valid/reliable measure of positive alcohol 
consequences.[57]
Brief Young Adult Alcohol Consequences Questionnaire (BYAACQ): Valid/reliable 
measure of negative alcohol consequences. [81]
Protective Strategies Questionnaire (PSQ): Valid/reliable measure of direct and indirect 
strategies for reducing alcohol consumption and consequences. [83]
Alcohol daily diaries: subjects will record the timing and amount of alcohol use before 
bedtime.[71]
Physical Fitness/Activity: Self-reported assessments with validity against objective 
measures. [74, 75]
Intervention Feasibility/Acceptability: OURATM use metrics; quantitative and qualitative 
ratings of OURATM and diary self-monitoring and health feedback/advice components 
using treatment evaluation surveys and exit interviews (e.g., ease of use, helpfulness, 
satisfaction, suggestions for improvement).
3.2.2
3.2.3
Secondary and Exploratory Outcome Variables (if applicable)
PROMIS™ Sleep-Related Impairment and Sleep Disturbance: Valid/reliable measures 
of perceived alertness, sleepiness, during waking hours and functional impairments due 
to sleep problems and perceived sleep quality/satisfaction and difficulty 
initiating/maintaining sleep.[58]
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Sleep daily diaries: subjects will rate their sleep quality upon waking.[72]
PROMIS™ Positive Affect/Depression/Anxiety: Valid/reliable measures of well-being, 
negative affect.[57, 73]
Physical Fitness/Activity: Self-reported assessments with validity against objective 
measures. [74, 75]
Morningness/Eveningness (ME) Questionnaire: Valid/reliable measure for degree of 
alertness during different points in the day. [80]
Munich ChronoType Questionnaire (MCTQ): Valid/reliable measure for how individuals 
sleep and wake. [80]
Theory of Planned Behavior (TPB): Valid/reliable measure for predicting risky drinking 
behavior. [78,79]
Dietary Screening Questionnaire (DSQ): Valid/reliable measure of dietary intake. [82]
COVID-19 Experiences Questionnaire: Self-report assessment to measure the impact 
of COVID-19. [84]
Intervention Feasibility/Acceptability: OURATM use metrics; quantitative and qualitative 
ratings of OURATM and diary self-monitoring and health feedback/advice components 
using treatment evaluation surveys and exit interviews (e.g., ease of use, helpfulness, 
satisfaction, suggestions for improvement).
3.3
Study Population
Participants: We will recruit both male and female heavy-drinking (report alcohol use that 
exceeds NIAAA recommended daily drinking limits (i.e., ≥5 for men; ≥4 for women) at least 4 
times within the last 28 days at baseline but do not meet criteria for a severe alcohol use 
disorder) young adults (N=60; ages 18-25 years old) from the local community through 
online advertising/social media (e.g., Facebook, Instagram, Snapchat) and flyers and notices 
displayed around the local community and college campuses. 
. 
3.3.1
Number of Participants
Targeted for enrollment at Yale for this protocol: 60 subjects (Assessment group [n=30] and 
Feedback group [n=30]).
3.3.2
Eligibility Criteria/Vulnerable Populations
Prospective participants will be screened on initial eligibility criteria via a web-based 
screener on the study website. Our research group has successfully recruited 
participants, including heavy-drinking young adults utilizing these recruitment 
strategies.
Following completion of the pre-screener, research staff will contact potential 
subjects and inform them of their initial eligibility status. Those who meet initial 
criteria will attend an intake to provide written informed consent and complete final 
screening for inclusion/exclusion criteria. Eligible individuals will be randomized to 
their condition to begin immediately after intake. 
All research staff and research participants will be screened for COVID-19 
symptoms prior to entry into CMHC. These include: fever of 99.9°F or higher, 
cough, shortness of breath/difficulty breathing, fatigue, repeated shaking with chills, 
muscle pain or body aches, chills, headache, sore throat, new loss of taste or smell, 
congestion or runny nose, nausea or vomiting, or diarrhea. Research staff and 
research participants must additionally affirm that they have not been in close 
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proximity to anyone who is experiencing symptoms, or who have tested positive for 
COVID- 19, within 14 days of a scheduled in-person visit. Research staff and 
research participants will indicate whether they have traveled anywhere outside of 
Connecticut within 14 days prior to a scheduled in-person visit. Current Connecticut 
state guidance on quarantine requirements for those traveling into Connecticut from 
other states in the USA, or internationally, will be observed. This section will be 
updated as Connecticut and Yale guidelines change. 
Inclusion Criteria:
(1) 18-25 years of age 
(2) report ≥ 4 heavy drinking occasions in the past 28 days (i.e., ≥5 drinks on 1 
occasion for men; ≥4 for women) 
(3) report Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) scores 
indicative of risk of drinking harm (i.e., ≥7 for men; ≥5 for women) [70]
(5) English speaking 
(6) have a smartphone for syncing OURA™ data and receiving OURA™ feedback. 
An estimated 96% of young adults own a smartphone.[76]
Exclusion Criteria:
(1) history of a sleep disorder 
(2) night or rotating shift work; travel beyond 2 time zones in month prior and/or 
planned travel >2 time zones during study participation 
(3) clinically severe AUD in past 12 months defined by: a) history of seizures, 
delirium, or hallucinations during alcohol withdrawal; b) report drinking to avoid 
withdrawal symptoms or have had prior alcohol withdrawal treatment; c) required 
medical treatment of alcohol withdrawal in the past 6 months which is concluded 
through a clinical interview with either Dr. Fucito or Dr. Ash. 
(4) currently enrolled in alcohol or sleep treatment 
(5) current, severe psychiatric illness (i.e., bipolar disorder, schizophrenia, panic 
disorder, borderline personality disorder, organic mood or mental disorders, or 
suicide or violence risk) by history or exam which is verified by clinical interview with 
either Dr. Fucito or Dr. Ash.
(6) current DSM-V substance use disorder as obtained by clinical interview with 
either Dr. Fucito or Dr. Ash 
No fetuses, neonates, pregnant women, children, prisoners, institutionalized 
individuals, or others who may be considered vulnerable populations will be included.
4 Study Methods/Procedures 
4.1
Study Procedures
The goal of this study is to determine the feasibility and preliminary efficacy of this 
intervention for reducing drinking among heavy-drinking young adults, which if 
promising will lead to a larger trial of this approach. 
Young adults in our previous studies expressed strong interest in both sleep and 
health feedback. Our current R34-funded study is testing sleep feedback alone, and 
our goal is to develop a program that is appealing to young adults. We will use this 
information to optimize and automate future intervention iterations. Inclusion of a 
condition in which health feedback/advice is limited to the OURA™ mobile app. Our 
goal is to motivate alcohol behavior change. 
Screening: We will recruit and screen subjects using methods Dr. Fucito has used 
successfully for other studies of heavy-drinking young adults, including online ads/social 
media posts (e.g., Facebook, Instagram, Snapchat), and notices posted around local 
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colleges and the community. Interested individuals who contact investigators by phone 
or email or who respond to mobile ads will be directed to complete a 5-minute, web-
based pre-screening survey. Before completing the pre-screener, volunteers will provide 
informed consent. Following completion of the pre-screener, research staff will contact 
potential subjects and inform them of their initial eligibility status. Those who meet initial 
criteria will attend an intake to provide written informed consent and complete final 
screening for inclusion/exclusion criteria. Eligible individuals will be randomized to their 
condition to begin immediately after intake. 
Randomization to Condition: Dr. Gueorguieva will create the randomization list, 
stratified by gender and implemented through an electronic clinical trial management 
system to ensure allocation concealment.
Photoplethysmography (PPG) Sensor: For 6 weeks following randomization, all 
subjects will wear a marketed PPG sensor, OURATM, daily. We will obtain the following 
health data (i.e., sleep duration, efficiency, latency, awakenings, % of time in sleep 
stages, bed/wake times, HRV, RHR). PPG is a non-invasive, low-cost technology that 
uses a light source and a photodetector at the skin surface to measure physiological 
parameters such as RHR, HRV, temperature, motion, movement. [61] PPG sensors are 
easy to use, discrete, low cost, and suitable for use in non-clinical/research settings, 
thereby enhancing ecological validity. PPG, including OURA™, is reliable/valid for 
HRV/RHR[62-65] and sleep stage prediction relative to actigraphy and PSG.[49, 50, 66-
68]
At intake, the Research Coordinator will demonstrate how to wear and charge the 
OURATM (device needs charging every 7 days). To encourage OURA™ adherence, we 
will provide daily reminders and support including when to recharge, and compensation 
for wearing and returning them, which we used successfully in our other studies. We will 
monitor OURATM use for all subjects through the OURATM Teams dashboard. Subjects 
in Assessment will not have access to the OURATM mobile app. We will sync their data 
to one of our study phones at the Week 6 visit. The OURATM ring can hold 6-weeks of 
data. Subjects in Feedback will have the OURATM mobile app downloaded on their 
phone to sync their data daily and receive immediate health feedback. They will then 
receive 3 electronic feedback reports sent via text/email at Weeks 2, 4 and 6, for which 
we will use the OURATM Teams dashboard. 
Diary Self-Monitoring: All subjects will complete daily alcohol and sleep diaries for 6 
weeks following intake, using diaries from our current R34-funded study. We will 
program diaries in MEI Research and send links via text message each morning. To 
encourage adherence, we will compensate subjects $1 for each completed daily diary, a 
successful strategy in our prior research. We will monitor use via the MEI Research  
dashboard.
Follow-up Visits and Exit Interviews: At Weeks 6 and 10, all subjects will complete 
follow-up visits remotely via ZOOM (HIPAA-compliant and password-protected) which 
will be recorded using ZOOM with subjects’ consent. Using remote procedures to 
conduct follow-up visits for our current R34-funded study and prior studies has resulted 
in very high retention (i.e., 95%). Follow-up visits will assess alcohol use, health 
characteristics, and the feasibility and acceptability of self-monitoring activities and 
health feedback/advice. At the Week 6 follow-up, we will conduct exit interviews to 
evaluate helpful components. For subjects in the assessment group, we will also sync 
their OURA TM data to the study phone at Week 6.
Randomization: 
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Subjects will be randomly assigned to 1 of 2 conditions: (1) Assessment (n=30) or (2) 
Feedback (n=30). The Assessment group will not have access to the OURA™ mobile 
app and will not receive any health feedback. The Feedback group will have access to 
the OURA™ app and will receive feedback. The OURA™ app provides daily summaries 
of HRV, RHR, and sleep that subjects can view on the app. In addition, every 2 weeks, 
we will send a written report via text/email that: (1) summarizes subjects’ alcohol use 
and the links with their HRV/RHR/sleep data and (2) provides health advice tailored to 
this data.
Intervention Conditions: Eligible subjects will be randomized to: (1) Assessment or (2) 
Feedback. All subjects will begin wearing an OURA™ right after intake and will 
complete daily diary assessments. 
Assessment (A) (n=30): Subjects in this group will only monitor their health/behaviors 
and will not receive any health feedback or advice. They will wear the OURA™ daily 
and complete daily electronic diaries about bedtime behaviors (e.g., amount/timing of 
alcohol use) and their sleep for 6 weeks. Diaries will be programmed in MEI Research  
and sent via text message each morning, a successful procedure for our current R34-
funded study. These subjects will not have access to the OURATM mobile app. We will 
sync their data to one of our study phones at the Week 6 visit. The OURATM ring can 
hold 6-weeks of data.
Feedback (F) (n=30): Subjects in this group will monitor their health/behaviors and will 
receive health feedback and advice. Subjects will wear the OURA™ daily and complete 
daily MEI Research  diaries for 6 weeks. They will also have access to the OURA™ 
mobile app. Subjects will receive the following daily health information from the OURA™ 
app: (1) HRV, RHR, sleep (i.e., duration, efficiency, latency, sleep stages, timing, 
wakefulness), body temperature, respiratory rate, and physical activity (i.e., steps, 
calories burned); (2) composite scores from 0-100 (≥85 optimal) for “Sleep”, “Activity”, 
and “Readiness” (i.e., overall measure of recovery, based on HRV, that signals capacity 
to perform at physical, mental, cognitive best); and (3) advice regarding optimal 
bedtime, activity progress, inactivity, and recovery. At intake, we will orient subjects to 
OURA™ app health feedback and advice. At Weeks 2, 4, and 6, subjects will receive 
written reports sent via a text/email link that summarizes their alcohol use (e.g., drinks 
per week, # of heavy occasions, peak BAC) and the links between drinking and 
OURA™ health outcomes as well as tailored advice for improving health, including 
evidence-based brief content for alcohol (e.g., standard drinks, low risk drinking 
guidelines, BAC feedback, controlled drinking tips) [40-42] and sleep (e.g., sleep 
hygiene, stimulus control).[19, 53, 54, 59, 60] We will derive these reports using the 
OURA™ Teams dashboard and daily diaries; subjects will not have dashboard access.
b.
Sources of Materials
b.1.The research material and data that will be collected include self-reports, interviews, 
sensor data.
b.2.These materials will be used to determine study eligibility and obtain information 
about drinking, health and sleep, and other related assessments.
b.3.The principal investigator and her designates will have access to individually 
identifiable private information. We will code research data by a number that does not 
include identifiable private information. All investigators and key personnel are required 
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to take the Yale University HIPAA training. Documentation of this training is required 
before research staff are allowed to take part in research activities.
b.4.The specimens and data are collected directly from the participants as described 
above (b.1.) specifically for the purpose of this project.
4.1.1
Data Collection 
Socio-demographic information: Will be assessed with interviews and self-reported 
age, race/ethnicity, marital & occupational status, education. 
Diagnostic/Substance Use History: Dr. Fucito, a licensed clinical psychologist, will 
Describe how and where the data will be recorded and identify all sources of data. This description 
should be specific but not over-detailed. However, you must make sure that data collected supports 
the objectives and endpoints stated above. Indicate whether:
•
The information obtained will be recorded by the investigator in such a manner that the 
identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to 
the subjects; OR
•
If any disclosure of the human subjects' responses outside the research would not reasonably 
place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, 
employability, educational advancement, or reputation; OR
•
If the information obtained is recorded by the investigator in such a manner that the identity of 
the human subjects can readily be ascertained, directly or through identifiers linked to the subjects.
Specify any assessments being used including methods and timing for assessing, recording and 
analysis.
Include any questionnaire administration and identify the questionnaire to be used for the study 
related assessment. State how these assessments contribute to the overall study aims. Include as 
appendices copies of each questionnaire.
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conduct the Mini International Neuropsychiatric Interview (The M.I.N.I.). [69]
Alcohol Use Disorders Identification Test-Consumption (AUDIT-C): Reliable/valid 
alcohol use screener to confirm at-risk drinking inclusion criterion based on cut-off scores 
for young adults.[70]
Alcohol Use 
Timeline Follow-
back Interview 
(TLFB): 
Valid/reliable/standardized interview to obtain alcohol quantity/frequency estimates [56]for 
a 30-day period prior to enrollment in the study and monthly following intake for a total of 
3 months.(51) Calendar prompts and memory aids (e.g., holidays) are used to facilitate 
accurate recall of substance use during the targeted period. We will derive the following 
30-day summary variables for: total drinks, drinks per drinking day, % heavy and 
abstinent days. 
PROMIS™ Alcohol Consequences: Valid/reliable measure of positive alcohol 
consequences.[57]
Brief Young Adult Alcohol Consequences Questionnaire (BYAACQ): Valid/reliable 
measure of negative alcohol consequences. [81]
Protective Strategies Questionnaire (PSQ): Valid/reliable measure of direct and indirect 
Table 1. Schedule of Assessments
Variables
Assessments
Intak
e
Intake-Wk 
6
6, 10
Demographics 
X
 
X
The M.I.N.I.
X
Eligibility/
Lab/
Medical
AUDIT-C
X
TLFB 
X
6, 10
PROMIS™ measures
X
6, 10
BYAACQ
X
6,
10
PSQ
X
6,10
TPB
X
6
DSQ
X
6,10
Munich Chrono Type 
Questionnaire
X
ME Questionnaire
X
Physical fitness 
X
6, 10
Alcohol/sleep diaries
X
COVID-19 Experiences 
Questionnaire
X
6,10
Alcohol/
Health 
Outcomes
OURATM HRV, RHR, sleep 
X
Feasibility
OURA™ use metrics
X
Acceptability
Treatment eval; exit 
interview
6
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strategies of reducing alcohol consumption and consequences. [83]
Theory of Planned Behavior (TPB): Valid/reliable measure for predicting risky drinking 
behavior. [79,79]
Alcohol daily diaries: subjects will record the timing and amount of alcohol use before 
bedtime.[71]
Health Characteristics
PROMIS™ Sleep-Related Impairment and Sleep Disturbance: Valid/reliable measures 
of perceived alertness, sleepiness, during waking hours and functional impairments due 
to sleep problems and perceived sleep quality/satisfaction and difficulty 
initiating/maintaining sleep.[58]
Sleep daily diaries: subjects will rate their sleep quality upon waking.[72]
PROMIS™ Positive Affect/Depression/Anxiety: Valid/reliable measures of well-being, 
negative affect.[57, 73]
Physical Fitness/Activity: Self-reported assessments with validity against objective 
measures. [74, 75]
Morningness/Eveningness (ME) Questionnaire: Valid/reliable measure for degree of 
alertness during different points in the day. [80]
Munich Chrono Type Questionnaire (MCTQ): Valid/reliable measure for how individuals 
sleep and wake. [80]
Dietary Screening Questionnaire (DSQ): Valid/reliable measure of dietary intake. [82]
COVID-19 Experiences Questionnaire: Self-report assessment to measure the impact 
of COVID-19. [84]
Intervention Feasibility/Acceptability: OURATM use metrics; quantitative and qualitative 
ratings of OURATM and diary self-monitoring and health feedback/advice components 
using treatment evaluation surveys and exit interviews (e.g., ease of use, helpfulness, 
satisfaction, suggestions for improvement).
4.1.2
Adverse Events Definition and Reporting
Dr. Fucito, the principal investigator is responsible for monitoring the data, assuring protocol 
compliance, and conducting monthly safety reviews. During the review process, Dr. Fucito, 
will evaluate whether the study should continue unchanged, require 
modification/amendment, or close to enrollment. 
Dr. Fucito, the Institutional Review Board (IRB) or NIH have the authority to stop or suspend 
the study or require modifications. 
This protocol presents minimal risks to the subjects and Unanticipated Problems Involving 
Risks to Subjects or Others (UPIRSOs), including adverse events, are not anticipated. In the 
unlikely event that such events occur, Reportable Events (which are events that are serious 
or life-threatening and unanticipated (or anticipated but occurring with a greater frequency 
than expected) and possibly, probably, or definitely related) or Unanticipated Problems 
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Involving Risks to Subjects or Others that may require a temporary or permanent interruption 
of study activities will be reported immediately (if possible), followed by a written report within 
48 hours of Dr. Fucito becoming aware of the event to NIAAA and within 5 days per the 
guidelines of the Yale IRB (using the appropriate forms from the website) and any 
appropriate funding and regulatory agencies.
Dr. Fucito will apprise fellow investigators and study personnel of all UPIRSOs and adverse 
events that occur during the conduct of this research project. Dr. Fucito will hold weekly 
study meetings with investigators to review study progress, including any adverse events. 
Investigators who are not present at these meetings will be alerted via email by Dr. Fucito. 
The protocol’s research monitor(s), e.g., the Yale IRB and NIH will be informed of any 
adverse events that meet these 3 criteria: (1) unexpected, (2) related/possibly related to 
study participation, and (3) places subjects or others at greater risk of harm than previously 
known/recognized. These adverse events will be reported within 48 hours of the event 
becoming known to Dr. Fucito.
4.2
Study Schedule
Intake (Week 0): 
Prior to attending the intake and upon arrival, subjects will be screened for COVID-19 
symptoms. These include fever of 99.9°F or higher, cough, shortness of breath/difficulty 
breathing, fatigue, repeated shaking with chills, muscle pain or body aches, chills, headache, 
sore throat, new loss of taste or smell, congestion or runny nose, nausea or vomiting, or 
diarrhea. We will also discuss COVID-19 risks with you. Subjects will then be asked to 
complete a number of questionnaires and self-assessments that will ask them about Their 
sleep, alcohol use, health behaviors, mood, and psychological characteristics. We will also 
ask for demographic information including age, race, socioeconomic status, and educational 
and occupational levels. A licensed clinical psychologist will conduct an interview with them 
to determine their substance use history and other relevant medical and psychiatric history. 
We will measure their height and weight. This visit will take about 1 hour. 
Randomization (Week 0): Subjects will be randomly assigned (like the flip of a coin) to 1 of 
2 conditions: (1) Assessment or (2) Feedback. 
If they are assigned to the Assessment group, they will wear the OURA™ ring and complete 
daily diaries for 6 weeks but will not have access to the OURA™ mobile app and will not 
receive any feedback about their health data. They will have an opportunity to receive this 
health data after they complete their final follow-up visit at Week 10. 
If they are assigned to the Feedback group, subjects will wear the OURA™ ring and 
complete daily diaries for 6 weeks. During this time, they will have access to the OURA™ 
mobile app and will receive personalized feedback and tailored health tips about their data. 
Treatment Phase (Intake-Week 6): They will begin wearing the OURA™ after the intake 
every day for a 6-week period. During these weeks, monitoring will occur continuously with 
the OURA™ and subjects will also complete daily diaries using the MEI Research 
application. We will arrange to pick up the biosensor from them at the end of the 6-week 
monitoring period. If they are in the Feedback group, subjects will also receive health 
feedback and advice through the OURA™ mobile app and reports that are sent to . The 
OURA™ app provides daily summaries of their resting heart rate, heart rate variability, and 
sleep that they can view on the app. The research staff will orient them to the OURA™ app 
health feedback and advice. In addition, every 2 weeks (i.e., Weeks 2, 4, and 6), we will 
send a written report via text/email that: (1) summarizes their alcohol use and the links with 
their heart and sleep health data and (2) provides health advice tailored to this data.
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Follow-up (Week 6): Subjects will complete the Week 6 follow-up visit remotely via ZOOM, 
which will be recorded using ZOOM with their consent. The research staff will conduct exit 
interviews and treatment evaluation surveys to understand the feasibility/acceptability of the 
health intervention program including wearing the biosensor. They will also complete 
questionnaires and interviews about their alcohol use, health characteristics, and the 
feasibility and acceptability of self-monitoring activities and health feedback/advice.  
Follow-Up (Week 10): Subjects will also complete the Week 10 follow-up visit remotely via 
ZOOM, which will be recorded using ZOOM with their consent. They will complete 
questionnaires and interviews about your alcohol use and health characteristics.
4.3
Informed Consent
After giving consent via a web-based screener, potentially eligible participants will be invited 
for an in-person intake visit. At the start of the initial intake session, informed consent to 
participate will be obtained from all participants after the research procedures and risks 
associated with participation have been explained. The entire consent form will be reviewed 
in detail with the participant in a private, one-on-one setting at the intake appointment with a 
research staff member. All risks and potential benefits will be described and discussed. The 
consent form will provide clear and explicit language about the intervention components, 
diary monitoring procedures, and sensor use. Any questions that the participant may have 
will be addressed. If the participant wishes, they may take the consent form home and 
consider it further before signing. They may also request to speak to anyone on the research 
team about questions they have or to consult others, including their physician and family 
members. Participants will sign 2 copies of the consent, retain one, and the researchers will 
keep the second copy on file. 
Participants will then complete all assessments to determine eligibility. Participants will 
be informed that they are free to decline participation and withdraw from the study at any 
time and that neither action will adversely affect their relationship with any study 
personnel. Following resolution of any questions, the participant will be asked to sign the 
consent form, if he/she agrees to participate.
4.3.1
Screening (if applicable) 
We will recruit and screen subjects using methods Dr. Fucito has used successfully for 
other studies of heavy-drinking young adults, including online ads/social media posts 
(e.g., Facebook, Instagram, Snapchat), and notices posted around local colleges and 
the community. Interested individuals who contact investigators by phone or email or 
who respond to mobile ads will be directed to complete a 5-minute, web-based pre-
screening survey. Before completing the pre-screener, volunteers will provide informed 
consent. Following completion of the pre-screener, research staff will contact potential 
subjects and inform them of their initial eligibility status. Those who meet initial criteria 
will attend an intake to provide written informed consent and complete final screening 
for inclusion/exclusion criteria. Eligible individuals will be randomized to their condition 
to begin immediately after intake. 
4.3.2
Recruitment, Enrollment and Retention (if applicable)
Interested individuals who contact investigators by phone or email or who respond to 
mobile ads will be directed to complete a 5-minute, web-based pre-screening survey. 
Before completing the pre-screener, volunteers will provide informed consent. Following 
completion of the pre-screener, research staff will contact potential subjects and inform 
them of their initial eligibility status. Those who meet initial criteria will attend an intake to 
provide written informed consent and complete final screening for inclusion/exclusion 
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criteria. Eligible individuals will be randomized to their condition to begin immediately 
after intake. 
The PI and research staff will recruit potential subjects
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as required 
by U.S. Law. This website will not include information that can identify the subject. At most, 
the website will include a summary of the results. The subject can search this website at any 
time.
4.3.3
Study Visits (is applicable)
4.4
Statistical Method
4.4.1
Statistical Design
Dr. Gueorguieva, a biostatistician, will oversee data analyses. We will use a type I error of 
5% (two-sided) significance testing using SAS V9.4 (SAS Institute, Cary, NC). We will 
examine data for conformity to the normal distribution and transformation or non-parametric 
methods will be used if necessary.
4.4.2
Sample Size Considerations
Sample Size and Power Calculations: The goal of this proof-of-concept proposal is to 
determine the feasibility and preliminary efficacy of this intervention for reducing drinking 
among heavy-drinking young adults, which if promising will lead to a larger trial of this 
approach. We propose to recruit 60 subjects (30 per group), in line with the recommended 
sample size of 15-30 subjects per group for Phase 1 behavioral intervention studies. [78] 
This sample size is feasible to recruit within the time period, will allow us to derive effect size 
estimates for primary and secondary outcomes to inform a more definitive study, and is 
sufficient for detecting a clinically significant, large difference between groups in total drinks 
controlling for baseline with 80% power at a 2-sided 0.05 significance level
4.4.3
Planned Analyses
Table 1. Schedule of Assessments
Variables
Assessments
Intake
Intake-Wk 6
6, 10
Demographics 
X
 
X
The M.I.N.I.
X
Eligibility/
Lab/
Medical
AUDIT-C
X
TLFB 
X
6, 10
PROMIS™ measures
X
6, 10
Physical fitness 
X
6, 10
BYACCQ
X
6,
10
PSQ
X
6,10
TPB
X
6
X
6,
10
DSQ
X
6,10
Munich Chrono Type 
Questionnaire 
X
ME Questionnaire
X
Alcohol/sleep diaries
X
COVID-19 Experiences 
Questionnaire
X
6,10
Alcohol/
Health 
Outcomes
OURATM HRV, RHR, sleep 
X
Feasibility
OURA™ use metrics
X
Acceptability
Treatment eval; exit interview
6
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Statistical analyses will utilize an ITT approach and mixed models, one of two gold standards 
(together with multiple imputation) for handling missing outcome data in longitudinal studies. 
For Primary Aim 1, we will examine condition effects on total drinks consumed over Weeks 
2-10 (summarized over 4-week periods), controlling for baseline drinks. For this analysis, we 
will use mixed effects models with condition and sex as between-subject factors and time as 
a within-subject factor. We will also use the same modeling approach for secondary alcohol 
outcomes: drinks per drinking day, % heavy drinking, abstinent days (summarized in 4-week 
periods), and alcohol-related consequences, controlling for baseline, and will focus on effect 
size estimation rather than statistical testing. Using all repeated measures on individuals in 
the context of a mixed model will allow us to assess temporal patterns of change over time 
and to use all available data on individuals. Thus, this approach helps to avoid imputation of 
missing data and allows us to obtain unbiased and efficient estimates of the main and 
interactive effects. Mixed models will account for the correlation in alcohol outcomes 
measured in the same individual. We will use the Schwartz-Bayesian Information Criterion to 
elect the best-fitting variance-covariance structure. We will consider time as a categorical 
factor but will also test whether alcohol outcomes change linearly by condition over time. If 
an alcohol outcome is not normally distributed, we have several options including 
transforming data, utilizing alternative methods (e.g., generalized linear mixed models, 
nonparametric tests, Poisson and negative binomial generalized linear mixed models for 
count data). Hypothesis: The feedback group will report fewer total drinks than the 
assessment group. 
For Secondary Aims 2.1-2.2, we will examine condition effects on PROMIS™ sleep quality 
and sleep-related impairment self-ratings, controlling for baseline, using mixed effects 
models. We will also analyze OURA™ sleep, HRV, and RHR data (summarized over 2-week 
periods) using mixed effects models. We will transform or utilize alternative methods for non-
normally distributed outcomes. We will also characterize the daily variations in OURA™ 
sleep, HRV, RHR data and potential dynamic relationships between them and daily diary 
drinking data using methods for longitudinally intensive data (e.g., time-varying effects 
models). Hypothesis: The feedback group will report better sleep/health than the assessment 
group. 
For Secondary Aim 2.3, we will summarize interview themes. We will also summarize use 
metrics and ratings for feedback and/or monitoring using descriptive statistics. We expect 
higher scores in the feedback group.
4.4.4
Analysis of Subject Characteristics (if applicable)
We will use descriptive statistics were used to summarize frequencies and 
percentages of sociodemographic characteristics (age, race, ethnicity, gender, college 
status) and clinical characteristics (drinking, sleep, and other health behaviors). 
4.4.5
Interim Analysis (if applicable)
N/A
4.4.6
Handling of Missing Data
We will also use the same modeling approach for secondary alcohol outcomes: drinks per 
drinking day, % heavy drinking, abstinent days (summarized in 4-week periods), and 
alcohol-related consequences, controlling for baseline, and will focus on effect size 
estimation rather than statistical testing. Using all repeated measures on individuals in the 
context of a mixed model will allow us to assess temporal patterns of change over time and 
to use all available data on individuals. Thus, this approach helps to avoid imputation of 
missing data and allows us to obtain unbiased and efficient estimates of the main and 
interactive effects. Mixed models will account for the correlation in alcohol outcomes 
measured in the same individual. We will use the Schwartz-Bayesian Information Criterion to 
elect the best-fitting variance-covariance structure. We will consider time as a categorical 
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factor but will also test whether alcohol outcomes change linearly by condition over time. If 
an alcohol outcome is not normally distributed, we have several options including 
transforming data, utilizing alternative methods (e.g., generalized linear mixed models, 
nonparametric tests, Poisson and negative binomial generalized linear mixed models for 
count data).
5 Trial Administration 
5.1
Ethical Considerations: Informed Consent/Assent and HIPAA Authorization
Consent forms will be Institutional Review Board (IRB)-approved and the participant will be 
asked to read and review the document. The members of the research team will explain the 
research study to the participant and answer any questions that may arise. This 
conversation will take place in a private room.
Participants will have the opportunity to carefully review the written consent form and ask 
questions prior to signing. The participants should have the opportunity to discuss the study 
with their family or surrogates or think about it prior to agreeing to participate. The participant 
will sign the informed consent document prior to any procedures being done specifically for 
the study. Participants must be informed that participation is voluntary and that they may 
withdraw from the study at any time, without prejudice. A copy of the informed consent 
document will be given to the participants for their records
We will not be enrolling participants with limited decision-making capacity. We plan to 
exclude individuals with current serious psychiatric or medical illnesses. The research 
assistant will read and review the consent form either in-person or via televideo while 
COVID-19 social distancing requirements remain in place. Due to the ongoing COVID-19 
This section should include any applicable ethical considerations.  They should also be addressed in the 
Informed Consent form, including if informed consent and/or HIPAA authorization will be obtained or a waiver of 
informed consent and/or HIPAA authorization will be requested. The Informed Consent form should be included 
as an attachment to the protocol.
Describe the following:
•
Any possible deception
•
Rationale if payment will be provided for participation.
•
Any sensitive data that may be collected and how it will be protected.
•
Any possibility that a previously unknown condition (disease, genetic disposition, etc.) will be 
discovered as the result of the study procedures and how this will be handled.
•
Any information that may be added to the subject's permanent medical records with rationale.
•
If informed consent/assent and HIPAA authorization will be obtained, the following should be 
addressed:
•
Who will obtain consent/authorization
•
When and where will the consent/authorization discussion occur
•
How will subject privacy be assured
•
How will consent/authorization be documented
•
How will subject understanding of the study be assessed
•
What steps are in place to avoid subject coercion
If your study involves children, additional information should be provided to describe:
•
How parental permission will be obtained
•
From how many parents will parental permission be obtained
•
Whether permission will be obtained from individuals other than parents, and if so, who will be 
allowed to provide permission.  The process used to determine these individual's authority to 
consent for the child should be provided
•
Whether or not assent will be obtained from the child
•
How will assent be documented
•
Whether child subjects may be expected to attain legal age to consent to the procedures for 
research prior to the completion of their participation in the research.  If so, describe the process 
that will be used to obtain their legal consent to continue participation in the study.  Indicate what 
will occur if consent is not obtained from the now-adult subjects.  
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pandemic, it is not always possible to consent a new study participant in person. Due to this, 
many participants will be consented via televideo, therefore a physical consent form will not 
be signed by the participant. Instead, a REDCap consent will be created, where participants 
will be able to view the entire consent form and then electronically sign/date/initial the 
consent form. The research assistant will share their screen while on televideo so the 
consent form can be read along with the participant. This is to explain the study in detail to 
the participant, so they are aware of all aspects of the study and fully informed. Participants 
will be able to ask research staff any questions during this consenting period. The research 
assistant will then ask the potential participant various questions about the consent form and 
study protocol to ensure the prospective participant sufficiently understands the study and 
the nature of their consent to participate. If concerns arise that a potential individual does not 
have sufficient capacity to provide informed consent, we will have a clinical member of the 
team conduct a mini mental status exam to verify capacity. We will allow sufficient time for 
research staff to explain the study and potential participants to review the consent, study 
procedures, and ask questions to avoid coercion.
The data will be stored in a locked room for 7 years after the final data is collected. After 
this point, the Data Manager and Principal Investigator, Dr. Fucito, will oversee the process 
in which data is destroyed or de-identified.
We have obtained a Certificate of Confidentiality (CoC) issued by the NIH. Once granted, the 
researchers can use this Certificate to legally refuse to disclose information that may
identify the participant in any federal, state, or local civil, criminal, administrative, legislative, 
or other proceedings, for example, if there is a court subpoena. The researchers will use the 
Certificate to resist any demands for information that would identify the participant, except as 
explained below.
The protection offered by the CoC does not stop the research team from voluntarily reporting 
information about suspected or known sexual, physical, or other abuse of a child or older 
person, or a participant’s threats of violence to self or others. If any member of the research 
team is given such information, he or she will make a report to the appropriate authorities. 
When the CoC is obtained, we will inform all active study participants.
The anticipated funding for this study is from an NIH grant (R21AA028886).
Even when a CoC is in place, the participant and their family members must still continue to 
actively protect their own privacy. If they voluntarily give their written consent for anyone to 
receive information about their participation in the research, then we may not use the CoC to 
withhold this information.
Participants will be paid $30 for completing the intake, $45 for completing the week 6 
follow-up visit, and $60 for completing the week 10 follow-up visit, total=$135. 
Participants will also be compensated for at-home monitoring activities: (1) $1 per day 
for wearing the OURA (42 possible days for a total of $42), (2) $50 for returning the 
OURA, and (3) $1 per day for completing each daily diary (42 possible days for a total of 
$42). The total possible compensation for at-home monitoring is $94.  Therefore, the 
total possible compensation for participants is $279. Participants will be registered 
through Oncore to receive payments for taking part in the study. We will use a Bank of 
America pre- paid debit card to provide payment. We will have to share participant 
name, address, and telephone number with Bank of America for ePayments and this 
information is communicated in the consent form. The participant will receive a card in 
the mail with the first payment. Each additional payment will be automatically added to 
the card.
5.2
 Institutional Review Board (IRB) Review
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The protocol will be submitted to the IRB for review and approval. Approval of the protocol 
must be obtained before initiating any research activity. Any change to the protocol or study 
team will require an approved IRB amendment before implementation. The IRB will 
determine whether informed consent and HIPAA authorization are required.
A study closure report will be submitted to the IRB after all research activities have been 
completed.
5.3
Subject Confidentiality
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s) and their interventions. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor.
All research activities will be conducted in as private a setting as possible.
The study monitor, representatives of the Institutional Review Board (IRB), or regulatory 
agencies may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) for the 
participants in this study. The clinical study site will permit access to such records.
At the end of the study, all records will continue to be kept in a secure location for 7 years.
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored on Yale redcap servers and in locked cabinets in 
locked office at CMHC. This will not include the participant's contact or identifying 
information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems 
used will be secured and password protected. At the end of the study, all study databases 
will be de-identified and archived on Yale servers and CMHC.
Identifiable information including participant’s name, address, phone number, and date of 
birth, will be collected and used to enroll and contact participants. It will only be used for 
this purpose. This information will be stored in locked cabinet apart from the research 
records. 
Research data will be collected using interviews, self-reports, wearable devices, and 
computer tasks. All identifiable information will be stored in a locked research cabinet. All 
participants will be assigned a study participant number. Subsequently, participants will be 
identified in the Case Report Forms (CRFs) only by that number and an encoded version of 
their initials (i.e., John Doe = JDO). A list of numbers and the corresponding names will be 
maintained by Dr. Fucito and stored in a locked research cabinet.
The data will be stored on secured server, laptop computer and desktop computer. The 
data will be stored in a locked room for 7 years after the final data is collected. After this 
point, the Data Manager and Principal Investigator, Dr. Fucito, will oversee the process in 
which data is destroyed or de-identified.
Several steps will be taken to safeguard the confidentiality of subjects and their data. All 
research data that is collected will be assigned a study participant number and that number 
will only identify participants in digital databases. The names of participants will not be 
associated with this data and assessments will be maintained according to participant study 
number. A master list connecting participant study numbers to participant names will be kept 
in a locked file cabinet where it can only be accessed by senior level project staff. Any 
information published as a result of the study will be such that it will not permit identification 
of any participant. 
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Right to privacy for participation in this research will be protected through alphanumeric 
coding of data (in place of names) and proper storage of research records, including 
treatment exit interviews. Collected materials will be maintained via an alphanumeric 
reference system maintained by Dr. Fucito. Participants’ names will appear only on the 
compound authorization form, and a master list maintained in a physically locked file that is 
separate from research data. Our data collection and management procedures are fully 
compliant with HIPAA. Access will be limited to personnel intimately involved in the study. A 
Certificate of Confidentiality will also be obtained from the National Institutes of Health to 
protect access to the records. However, participants will also be told that if they present with 
suicidal or homicidal ideation and/or report any form of child/elder abuse or report plans to 
damage property then we will have to report this to the appropriate authorities and/or provide 
them with referrals for immediate treatment. Electronic data will be de-identified, and 
password protected. Only members of the study team will have access to the physical or 
electronic data. 
For the wearable devices, data will only be linked to participants’ study numbers not the 
participants themselves. Only members of the study team will have access to the physical or 
electronic data. OURA™ data are deidentified and are also protected through secure, 
password-protected servers. We will use an alphanumeric code to sign participants up to the 
OURA™ mobile app in place of their names. After downloading the data, the data will be 
immediately deleted from the devices. OURA follows strict policy guidelines relating to both 
health privacy and teams privacy. OURA™ complies with all legal requirements regarding 
data sharing and only shares user information with trusted service providers. Users can 
withdraw consent from having their data collected at any time. OURA™ teams is a feature 
that allows health data to be shared with trusted individuals, such as healthcare 
professionals and researchers. There are safeguards in place to ensure this data is 
processed and collected efficiently and appropriately, users can withdraw from providing 
data to  OURA™ teams at any time. 
All investigators and key personnel have taken the required Yale University HIPAA 
training. Right to privacy for participation in this research will be protected through coding 
of data and proper storage of research records. A list of numbers and the corresponding 
names will be maintained by the Principal Investigator in a locked research cabinet.
Individually identifiable health information will be protected in accordance with the Health 
Insurance Portability and Accountability Act of 1996 and by additional protections of 
substance abuse treatment records afforded under Code of Federal Regulations (CFR) 
Part 2, Subpart E. All research personnel will be trained on human subjects’ protection and 
HIPAA procedures.
We may share participant information with:
•
The U.S. Department of Health and Human Services (DHHS) agencies
•
Representatives from Yale University, the Yale Human Research Protection Program 
and the Institutional Review Board (the committee that reviews, approves, and monitors 
research on human participants), who are responsible for ensuring research 
compliance.  These individuals are required to keep all information confidential. 
•
Those representatives at Yale who are responsible for the financial oversight of 
research including billings and payments
•
The Principal Investigator
•
The study sponsor
•
Laboratories and other individuals and organizations that analyze your health 
information in connection with this study, according to the study plan
•
Co-Investigators and other investigators
•
Study Coordinator and Members of the Research Team
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•
Other researchers through a shared data agreement through a required policy from 
NIAAA
5.4
Deviations/Unanticipated Problems
A protocol deviation is any noncompliance with the study protocol. The noncompliance may 
be either on the part of the participant, the investigator, or the study site staff. As a result of 
deviations, corrective actions are to be developed by the site and implemented promptly.
It is the responsibility of the site investigator to identify and report deviations within 2 working 
days of identification of the protocol deviation. All deviations must be addressed in study 
source documents, reported to the study sponsor, and the reviewing Institutional Review 
Board (IRB) per their policies.
Unanticipated problems involving risks to participants or others include, in general, any 
incident, experience, or outcome that meets all of the following criteria:
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that 
are described in the protocol-related documents, such as the Institutional Review Board 
(IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied;
Related or possibly related to participation in the research (“possibly related” means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused by 
the procedures involved in the research); and
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized.
The investigator will report unanticipated problems (UPs) to the reviewing Institutional 
Review Board (IRB) and to the study sponsor. The UP report will include the following 
information: 
Protocol identifying information: protocol title and number, PI's name, and the IRB project 
number;
A detailed description of the event, incident, experience, or outcome;
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;
A description of any changes to the protocol or other corrective actions that have been taken 
or are proposed in response to the UP.
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline:
UPs that are serious adverse events (SAEs) will be reported to the IRB and study sponsor, if 
applicable immediately (if possible) followed by a written report within 5 calendar days using 
the appropriate forms from NIH and Yale University IRB.
Any other UP will be reported to the IRB and study sponsor within 14 calendar days of the 
investigator becoming aware of the problem.
All UPs should be reported to appropriate institutional officials (as required by an institution's 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 30 calendar days  of the IRB's receipt of the 
report of the problem from the investigator.
5.5
Data Quality Assurance
Describe the quality control and assurance for the conduct of the study to ensure that Good Clinical 
Practice is followed. Any steps that will be implemented as part of the study to ensure standardization 
of the collection of accurate, consistent, complete and reliable data, such as training sessions, 
monitoring of investigator sites, instruction manuals, use of central laboratory or reading center should 
be included.
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Multiple measures are in place to ensure the validity and integrity of the data. First, all 
research staff receive Human Subjects Protection training, as well as training in Good 
Clinical Practice. Second, Dr. Fucito will supervise and train the Research Coordinator and 
key personnel on study procedures to ensure that all procedures are followed and are in 
compliance with the approved Yale University IRB protocol. Dr. Fucito will also provide 
training and oversight to study staff to ensure data are generated, documented, and reported 
according to requirements by the Yale University IRB and NIH. She will then monitor 
adherence to protocol procedures and use individual supervision to address any data quality 
concerns. Third, weekly research meetings will be held for all research staff as a forum for 
in-service training as well as to discuss questions regarding issues that arise in complex 
clinical research protocols. Fourth, all research staff will be cross-trained to ‘cover’ for each 
other; thus, review by multiple staff with oversight by the PI will facilitate early identification of 
errors and oversight. Fifth, Dr. Fucito will also oversee quality assurance of data. The 
Research Coordinator, in collaboration with Dr. Fucito, will review the study database on a 
monthly basis to ensure data accuracy. Any data quality issues will be addressed 
immediately. Last, the use of an electronic system for data capture will minimize data entry 
errors. 
5.6
Study Records

Protocol

Consent form

Alcohol/sleep diaries

Surveys 
5.7
Access to Source
Source data will be maintained per Medical Records policy in a password protected, secure, 
Health Insurance Portability and Accountability Act (HIPAA) compliant, web-based electronic 
database with a built-in audit trail.
Only Institutional Review Board (IRB) approved research team members who have current 
HIPAA and Collaborative Institutional Training Initiative (CITI) Good Clinical Practice (GCP) 
and human subjects protection training will be authorized to access records.
5.8
Data or Specimen Storage/Security
Data Acquisition and Transmission. We have selected psychometrically sound assessments 
that are brief and feasible with young adults and adequate to test study hypotheses. Trained 
research staff will administer assessments and collect measurements. They will enter data 
directly into a secure electronic database, which will be backed up on a secure, password 
protected Yale University network drive. De-identified data will be stored in the database and 
only accessible by research staff using a password protected login. All data with identifiable 
information will be stored in locked file cabinets in locked offices and will only be accessible 
by research staff. The transfer of any identifiable administrative data will be through Yale 
University’s secure, password-protected Secure File Transfer system. OURA™ data will also 
be de-identified and distributed to Yale through an agreement with OURA™ that ensures 
data confidentiality.
Specify the documents considered study records (subject diaries, regulatory documents, protocols, 
consents forms, case report forms, subject medical records, surveys, specimens, etc.).
Describe method in which data will be collected, stored (digital, hard copy, etc.) and maintained in a 
secure manner (encryption, password protection, etc.).
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Data Entry Method. Trained research staff will enter data directly into the electronic 
database. No personally-identifiable information will be entered into the electronic database, 
which will be stored on a secure, password protected Yale University network drive. 
5.9
Retention of Records
The data will be stored in a locked room for 7 years after the final data is collected. After 
this point, the Data Manager and Principal Investigator, Dr. Fucito, will oversee the process 
in which data is destroyed or de-identified.
5.10 Study Modification
Study modifications will be undertaken in response to ongoing study monitoring. Any 
potential modifications that could have a major impact on the study objectives will be 
discussed with the NIH Program Officer before submission to the IRB. More minor 
modifications that do not impact study objectives but help with study recruitment and 
implementation or allow for additional assessment of important questions will be submitted to 
the IRB for approval.
5.11 Study Monitoring
Dr. Fucito, the PI, will be responsible for monitoring the data, assuring protocol compliance, 
and conducting the safety reviews at the specified frequency that must be conducted at a 
minimum of every 6 months (including when reapproval of the protocol is sought), which is 
appropriate for a study deemed to be of minimal risk. Dr. Fucito will review the frequency of 
anticipated and unanticipated adverse events overall and by study arm with key personnel. 
The focus of the evaluation will be to determine whether the study should continue 
unchanged, require modification/amendment, continue or close to enrollment. Dr. Fucito, the 
Yale University IRB, and the National Institutes of Health have the authority to stop or 
suspend the study or require modifications. 
Dr. Fucito will also lead a weekly research meeting with key personnel to review the status of 
all enrolled participants and discuss the eligibility of potential participants. At this weekly 
meeting, Dr. Fucito will review study progress (i.e., recruitment goals, retention, protocol 
adherence). Any adverse events will be reviewed at this meeting including serious adverse 
events that may have been attended to outside of this weekly meeting. An annual progress 
report will be submitted to NIH and the Yale University IRB that lists and summarizes 
adverse events; documents whether adverse event rates are consistent with pre-study 
assumptions; summarizes recruitment and retention and reason for dropouts; and 
summarizes study progress related to the stated aims.
5.12 Study Completion
Intended to complete in 2 years. The IRB will be notified in writing upon study completion 
and the study will be archived with the IRB when all final analyses have been conducted on 
identifiable information.
5.13 Funding Source
The anticipated funding for this study is from an NIH grant (R21AA028886).
5.14 Conflict of Interest Policy
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will 
be required to have such conflicts managed in a way that is appropriate to their participation 
in the trial. The study leadership in conjunction with the appropriate conflict of interest review 
committee has established policies and procedures for all study group members to disclose 
all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest.
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Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by the [specify committee] with a Committee-sanctioned conflict 
management plan that has been reviewed and approved by the study sponsor prior to 
participation in this study.  All investigators will follow the applicable conflict of interest 
policies.
5.15 Publication Plan
Study results will be made available via articles written for professional and layperson 
publications; presentations at scientific and professional conferences; special lectures/talks 
in academic and professional settings; collaborating agencies/research sites, and interest 
groups. No identifiable information will be disclosed. Data will be presented and published 
in aggregate. Dr. Fucito, as PI, has primary responsibility for publishing the study results. 
She will acknowledge NIH grant funding for all presentations and publications and will 
ensure all publications are submitted to PMC in accordance with NIH’s policy on public 
access. 
Consistent with the NIH resource sharing policy, we will share data with other qualified 
investigators. Once all of the data have been cleaned and validated, and main findings 
have been published, the data will be made available to the scientific community. Datasets 
will be made available to any qualified individual who makes a direct request to the PI and 
indicates the data will be used for the purposes of research (as defined in CFR Title 45 
Part 46). Data will be provided to HIPPA-compliant, de-identified files. The following plan 
specifies the following conditions that need to be met before data are shared in the form of 
a data sharing agreement. 

A formal research question is specified a priori; 

Names, affiliations, and roles of any other individuals who will access the shared 
data;
 

The deliverable(s)—e.g., manuscript, conference presentation—are specified a priori; 

Proper acknowledgement of the source of the data; 

A statement indicating an understanding that the data cannot be further shared with 
any additional individual(s) or parties without the PI’s permission; 

IRB approval for use of the data (or documentation that the data are exempt);

Agreement to maintain the data in a physically and electronically secure location. 
Data will be shared in electronic format and accessible to the software used by the 
Investigators; upon completion of the analyses, the requestor will be instructed to destroy all 
copies of the data. 
The agreement to share data will be revisited annually to determine whether the current 
policy should be modified based upon our prior experiences in sharing the data with other 
investigators. 
In addition, consistent with new regulations for the NIAAA Data Archive (NIAAA(DA), all data 
will be shared with the NIAAA(DA). We will upload data to the NIAAA(DA) at least every 6 
months.
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Appendices
Appendix #
Title
Section
Topic
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List of Tables
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