Effect of Light Alcohol Intake on Sex Hormone Levels Among Postmenopausal Women With ER+ Breast Cancer on Aromatase Inhibitor Therapy: The Alcohol and Breast Cancer (ABC) Trial
Phase: NA
Conditions: ER+ Breast Cancer, Breast Cancer, Aromatase Inhibitors
Sponsor: Beth Israel Deaconess Medical Center

K01 Alcohol & Breast Cancer (ABC) Trial 
 
ClinicalTrials.gov NCT05423730 
 
Unique Protocol ID: 21-698  
 
Secondary IDs: K01AA027831 
 
Protocol Approved by Dana-Farber/Harvard Cancer Center on 1/19/2024 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
Page 1 of 29 
 
 
PROTOCOL TITLE: 
Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with 
ER+ Breast Cancer on Aromatase Inhibitor Therapy: The Alcohol and Breast Cancer (ABC) 
Trial 
 
*Sponsor-Investigator: 
 
Name: Kenneth J Mukamal 
 
Institution: Beth Israel Deaconess Medical Center 
 
e-mail address: kmukamal@bidmc.harvard.edu 
 
*Principal Investigators (PI): 
 
Name: Kenneth J Mukamal 
 
Institution: Beth Israel Deaconess Medical Center 
 
e-mail address: kmukamal@bidmc.harvard.edu 
 
 
VERSION NUMBER: 
2.1 
 
DATE: 1/16/2024 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
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Table of Contents 
1.0 Objectives* .......................................................................................................................... 3 
2.0 Background* 
........................................................................................................................ 3 
3.0 Inclusion and Exclusion Criteria* 
........................................................................................ 4 
4.0 Study-Wide Number of Subjects* 
....................................................................................... 5 
5.0 Study-Wide Recruitment Methods* .................................................................................... 5 
6.0 Multi-Site Research* ........................................................................................................... 5 
7.0 Study Timelines* 
................................................................................................................. 5 
8.0 Study Endpoints* 
................................................................................................................. 5 
9.0 Procedures Involved*........................................................................................................... 6 
10.0 Data and Specimen Banking* 
............................................................................................ 13 
11.0 Data Management* and Confidentiality 
............................................................................ 13 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
.................................... 17 
13.0 Withdrawal of Subjects* 
.................................................................................................... 19 
14.0 Risks to Subjects* 
.............................................................................................................. 19 
15.0 Potential Benefits to Subjects* 
.......................................................................................... 20 
16.0 Vulnerable Populations* 
.................................................................................................... 21 
17.0 Community-Based Participatory Research* 
...................................................................... 21 
18.0 Sharing of Results with Subjects* 
..................................................................................... 21 
19.0 Setting 
................................................................................................................................ 21 
20.0 Resources Available........................................................................................................... 22 
21.0 Prior Approvals 
.................................................................................................................. 24 
22.0 Recruitment Methods 
......................................................................................................... 24 
23.0 Local Number of Subjects ................................................................................................. 25 
24.0 Provisions to Protect the Privacy Interests of Subjects 
...................................................... 26 
25.0 Compensation for Research-Related Injury 
....................................................................... 27 
26.0 Economic Burden to Subjects 
............................................................................................ 27 
27.0 Consent Process 
................................................................................................................. 27 
28.0 Process to Document Consent in Writing 
.......................................................................... 28 
29.0 Drugs or Devices................................................................................................................ 29 
 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
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1.0 Objectives* 
Alcohol intake raises sex hormone levels, however, it is unknown if that 
effect persists in postmenopausal women with estrogen receptor-positive 
(ER+) breast cancer on aromatase inhibitor (AI) therapy, which is an 
estrogen suppressant. There have been no studies to examine alcohol’s 
effect on sex hormone levels among postmenopausal women with ER+ 
breast cancer receiving AI therapy. These drugs are only prescribed to 
postmenopausal women who had ER+ breast cancer, the subtype where 
alcohol has been found to increase breast cancer incidence. This information 
is needed for postmenopausal women with estrogen receptor-positive (ER+) 
breast cancer to make informed decisions about their alcohol intake and its 
potential effect on adjuvant AI therapy.  
 
To address this issue, we will conduct a pilot randomized controlled crossover trial 
of 20 postmenopausal women with estrogen receptor-positive (ER+) breast cancer 
who receive AI therapy and who consume at least one alcoholic drink per week but 
not more than one drink per day, to assess whether alcohol at low “real-world” 
levels of intake increases sex hormone levels in the presence of AI’s. 
 
We hypothesize that the expected within-person increases in sex hormone 
levels following light alcohol consumption will not be observed among 
women using aromatase inhibitor therapy throughout study enrollment.  
 
2.0 Background* 
Several controlled feeding studies among premenopausal and postmenopausal 
women showed that alcohol supplementation for a few weeks acutely increases 
estrogen and sex hormone-binding globulin (SHBG) levels. However, data on how 
light intake of alcohol impacts sex hormone levels among women receiving 
estrogen suppressants is critical for guiding postmenopausal women with estrogen 
receptor-positive (ER+) breast cancer about the safety of alcohol intake. 
 
In a cross-sectional study of 490 postmenopausal breast cancer survivors 
(Wayne S. Cancer Epidemiol Biomarkers Prev. 2008;17(11):3224-3232.), 
alcohol intake and sex hormone levels were strongly associated despite the 
relatively low range of alcohol intake in study participants. Tamoxifen use 
dampened the association between alcohol intake and 
dehydroepiandrosterone sulfate (DHEAS) levels, and among participants 
with ER+ tumors, there was no association between alcohol intake and sex 
hormone-binding globulin (SHBG). 
 
Although alcohol intake raises sex hormone levels, it is unknown if that effect 
persists on aromatase inhibitor therapy, in part because the mechanism underlying 
alcohol’s effect on sex hormone levels is not well understood. Despite the potential 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
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risks of alcohol intake on hormone levels, a cancer diagnosis is not associated with 
long-term changes in daily alcohol intake. Furthermore, there have been discrepant 
findings on the association between alcohol intake and breast cancer recurrence and 
survival. Some studies have found that alcohol intake is not associated with a higher 
rate of breast cancer mortality, and it may even lower the rate of all-cause mortality.  
 
There have been no studies to examine alcohol’s effect on sex hormone levels 
among postmenopausal women with estrogen receptor-positive (ER+) breast cancer 
receiving aromatase inhibitor therapy. This information is needed for them to make 
informed decisions about their alcohol intake and its potential effect on adjuvant 
aromatase inhibitor therapy. Therefore, we will conduct a pilot randomized 
controlled crossover trial to assess whether alcohol at low “real-world” levels of 
intake increases sex hormone levels in the presence of aromatase inhibitor therapy. 
 
3.0 Inclusion and Exclusion Criteria* 
We aim to identify postmenopausal women with estrogen receptor-positive (ER+) 
breast cancer who typically consume at least one alcoholic drink per week but not 
more than two servings per day and are currently prescribed aromatase inhibitors 
including anastrozole (Arimidex®), letrozole (Femara®), and exemestane 
(Aromasin®). These drugs are only prescribed to postmenopausal women who have 
been diagnosed with estrogen receptor positive (ER+) breast cancer, the subtype 
where alcohol has been found to increase breast cancer incidence. 
 
Inclusion Criteria: 
• ER+ breast cancer 
• Female sex at birth 
• Postmenopausal, either natural or induced 
• Self-reported consumption of at least one alcoholic drink per week but not more 
than two servings per day 
• Currently prescribed aromatase inhibitors including anastrozole (Arimidex®), 
letrozole (Femara®), and exemestane (Aromasin®) 
• Documented liver function test results below 1.5X the upper limit of normal within 
12 months of screening 
 
Exclusion criteria: 
• Self-reported consumption of more than two drinks per day, a previous or current 
history of alcohol abuse based on standard questionnaires (AUDIT≥8), or 
consumption of 4 or more drinks in one day within the last 6 months 
• Currently undergoing cytotoxic chemotherapy or radiation planned in the next two 
months 
• Any surgery planned in the next two months 
• Alcohol flushing syndrome  
• Current use of any pharmaceutical agent contraindicated with alcohol, including 
warfarin, dual antiplatelet therapy, and metronidazole 
• Hemoglobin A1c>8% or a fasting glucose result above 180 mg/dL within 6 months 
of screening 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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• Unable to speak or understand English 
• Unable to understand and provide informed consent, as judged by the study team 
• Uncertain ability to complete the protocol, as judged by the study team 
 
We will not include adults unable to consent, individuals who are not yet 
adults, pregnant women, or prisoners. 
 
4.0 Study-Wide Number of Subjects* 
Not Applicable. This is a single-site pilot trial. 
 
5.0 Study-Wide Recruitment Methods* 
Not Applicable. This is a single-site pilot trial.  
 
This pilot study is funded by very limited project funds from Dr. Mostofsky’s K01 award 
and comprises a total of 20 women – a small enough total to be readily completed at a 
single center.  Dr. Mostofsky, a research collaborator at BIDMC, will conduct 
recruitment herself at the BI oncology clinics.  As a result, expansion beyond BIDMC is 
not currently feasible on the project’s NIH-funded budget. 
 
6.0 Multi-Site Research* 
Not Applicable. This is a single-site pilot trial. 
 
7.0 Study Timelines* 
• Each participant will be involved in the study for ten weeks from the date 
of her screening visit.  
• We anticipate that it will take one year from the date of IRB approval to 
recruit and enroll enough women so that 20 women will have completed 
all study visits. 
• We anticipate that it will take 2 years from the date of IRB approval to 
complete the interviews, clean the data and prepare the primary analyses. 
 
8.0 Study Endpoints* 
We will examine within-person changes in blood levels of estradiol, 
testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-
binding globulin (SHBG) after three weeks of one serving of white wine 
daily compared to levels after three weeks of one serving of white grape 
juice daily. 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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At visits 1, 2, 3, and 4, the BIDMC Clinical Research Center (CRC) nurses will 
obtain a fasting blood sample. Within 72 hours, Quest Diagnostics will measure 
hepatic function, a complete blood count, and following visits 2 and 4, they will 
conduct a lipid panel. On our weekly phone check-ins, we will ask about recent 
health events such as unscheduled hospitalizations or any symptoms that have 
developed since the last meeting. 
 
9.0 Procedures Involved* 
This is an unblinded randomized controlled crossover trial to examine whether 3 
weeks of light alcohol consumption causes a short-term change in sex hormone 
levels compared to levels following 3 weeks of white grape juice consumption 
among postmenopausal women with estrogen receptor-positive (ER+) breast cancer 
taking an aromatase inhibitor. In this design, participants are compared to 
themselves at different times, with the sequence of the two treatment arms assigned 
by randomization. In other words, half of the women will be randomized to 
consume one serving of white wine every day for three weeks followed by one 
serving of white grape juice every day for three weeks, and half of the women will 
be randomized to three weeks of white grape juice followed by three weeks of 
white wine. To prevent a potential carryover effect of the drink in the first period 
affecting hormone levels in the second treatment period, we will ask participants to 
refrain from drinking any alcohol or grape juice for two weeks before starting each 
treatment arm. The women will know when they are supposed to drink the wine and 
when they are supposed to drink the grape juice. 
 
Recruitment:  
We will present the trial protocol and eligibility criteria at a meeting for the six 
medical oncologists and three nurse practitioners who provide outpatient care at the 
BIDMC BreastCare Center and ask for their assistance to recruit patients from their 
practice who may be eligible and interested in participating in our trial.  
 
We will review medical records for patients receiving care in the BreastCare Center 
or Healthcare Associates (HCA), BIDMC’s primary care practice, to see if they 
meet the eligibility criteria, and contact their health provider about their fitness to 
participate. Unless their provider recommends otherwise, we will mail an invitation 
letter to patients who appear to be eligible and ask them to contact us if interested. 
If they do so and remain interested, we will arrange a screening visit. We will also 
call participants who have received letters and have upcoming clinical appointments 
to remind them of the study and to determine if they would like to arrange a 
screening visit in conjunction with that appointment. We will also continue to place 
flyers and brochures in the BreastCare Center so that women who are interested in 
the study can reach out to us.  
 
We are submitting a request for a waiver of HIPAA authorization to obtain 
protected health information for potentially eligible women receiving care at the 
BIDMC BreastCare Center to confirm eligibility. Institutions will register eligible 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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participants in the Clinical Trials Management System (CTMS) OnCore as required 
by DF/HCC Policy REGIST-101.  
 
Screening Visit:  
If a referred patient is interested in learning more about the study, we will invite her 
to meet with a member of the research team in a private room at the BIDMC 
BreastCare Center. The study team member will explain the study, obtain informed 
consent, and confirm eligibility. An MD is not required for the consent process. No 
study procedures will be performed prior to obtaining informed consent. If the 
patient has not had liver function measured in the past 12 months, we will conduct a 
liver function test at their screening visit. If a hemoglobin A1c or fasting glucose 
test is not available, we will refer them to their physicians until we can document 
clinical control. We will obtain information on medical history, including an 
assessment of their usual frequency of alcohol consumption (using the Alcohol use 
Disorders Identification Test (AUDIT), the type of aromatase inhibitor therapy 
prescribed, and demographic and medical characteristics,  
 
Aromatase inhibitors are only prescribed to women who are postmenopausal, either 
naturally or artificially induced. If any women report that they are pre-menopausal, 
sexually active, and not using an effective form of contraception, we will counsel 
them that these medications are teratogenic and they will be referred back to their 
providers. Participants found ineligible will be thanked for their time but they will 
not be invited for the baseline visit (Study Visit 1). Either the primary investigator 
(Dr. Kenneth Mukamal) or another physician involved in the study will review the 
screening results to confirm eligibility. Eligible participants will begin a two-week 
run-in period in which they will refrain from alcohol and grape juice (washout 
period 1). 
 
Study Visit 1 (Baseline):  
If the participant confirms that she did not drink alcohol or grape juice for the past 
two weeks, she will return for visit 2 after fasting for 12 hours. The BIDMC CRC 
nurses will draw 100 mL (approximately 7 tablespoons) of blood for real-time 
processing of a basic metabolic panel and safety monitoring (complete blood count 
and hepatic panel). We will store the remaining sample for analyzing sex hormone 
levels as soon as all participants complete the study. The CRC nurses will conduct 
the blood draw, specimen processing, and transportation to Quest Diagnostics in 
accordance with their pre-specified procedures. 
 
The CRC research nurses will conduct safety monitoring at each study visit. Using 
their standard protocols, they will perform repeated measurements of vital signs, 
including height (at baseline), weight, systolic and diastolic blood pressure, and 
heart rate. They will measure supine blood pressure as the average of the final 2 of 
3 measurements following at least five minutes of rest using an automated cuff 
device calibrated at least monthly. They will measure weight with the participant 
wearing light clothing and standing on a digital scale with handrails.  
 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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Using the REDCap randomization module, we will randomly allocate women to a 
sequence of either white grape juice followed by white wine or to a sequence of 
white wine followed by white grape juice. One drinking period consists of 3 weeks 
of one serving (5 oz≈14 g alcohol) of white wine consumption daily and the other 
drinking period consists of 3 weeks of a calorically equivalent serving (6 ounces) of 
(alcohol-free) white grape juice. At the beginning of the white wine drinking 
period, the participants will receive one 3L box and one 500 mL box of Bota Box 
Chardonnay, a commercially available white wine that is 13% alcohol by volume 
for the three weeks of one serving (5 ounces) of white wine consumption daily. At 
the beginning of the white grape juice drinking period, the participants will receive 
one 96-ounce bottle and one 64-ounce bottle of Welch
's 100% White Grape Juice 
for the three weeks of a calorically equivalent serving (6 ounces) of (alcohol-free) 
white grape juice each day. There will be no blinding of the alcoholic beverages; all 
participants will know when they have been randomized to drink the white wine 
and when they have been randomized to drink the grape juice.  
 
After obtaining IRB approval, we will work with the CRC to finalize the plans to 
purchase, store and transfer the white wine and white grape juice to participants. 
We will distribute the three-week supply of wine or grape juice and a standardized 
labeled measuring cup to ensure that participants consume the correct amount each 
day. We will give the participants an information sheet, advising them to refrain 
from all alcohol and grape juice except their assigned drink and to maintain their 
typical patterns of diet and activity throughout the study. For the three weeks of 
white wine intake, we will advise participants to drink their daily serving at a time 
when they will not drive or operate machinery in subsequent hours. We will also 
provide a paper calendar for participants to record their daily alcohol and grape 
juice intake and tell them that we will review this calendar with them on our weekly 
phone calls. 
 
Study Visit 2:  
At the end of the 3-week drinking period, the participant will come to the BIDMC 
CRC, and a nurse will draw 90 mL (approximately 6 tablespoons) of blood for 
safety measures and sex hormone levels. They will also take vital signs and 
measure weight. We will ask participants to bring leftover drinks to this visit so that 
we can measure the remaining amount as an indicator of adherence. We will ask 
participants to refrain from drinking any alcohol or grape juice for the next two 
weeks (washout period 2).  
 
Study Visit 3:  
At the end of the 2-week washout period, the participant will come to the BIDMC 
CRC, and a nurse will draw 90 mL (approximately 6 tablespoons) of blood for 
safety measures and sex hormone levels. They will also take vital signs and 
measure weight. We will then distribute the second beverage to consume daily for 
the following 3 weeks. 
 
Study Visit 4:  

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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At the end of the 3-week drinking period, the participant will come to the BIDMC 
CRC, and a nurse will draw 90 mL (approximately 6 tablespoons) of blood for 
safety measures and sex hormone levels. They will also take vital signs and 
measure weight. We will ask participants to bring leftover drinks to this visit so that 
we can measure the remaining amount as an indicator of adherence.   
 
Blood Samples: The nurse will obtain blood samples in the morning after the last 
day of each 2-week washout period and each 3-week dietary period. We will 
schedule blood draws for time windows of up to ±4 days of the end of the prior 
washout or drinking period. If the visit is delayed for up to four days, we will ask 
participants to continue the protocol (washout, white wine, or white grape juice) for 
the additional days. At visit 1, the nurse will draw 100 mL (approximately 7 
tablespoons) of blood and at visits 2, 3, and 4, the nurse will draw 90 mL 
(approximately 6 tablespoons) of blood. They will draw one 10 mL tube for each of 
the 10 assays: complete blood count, hepatic function panel, basic metabolic panel 
(only at visit 1), DHEAS, FSH, LH, SHBG, estradiol, testosterone, and 
progesterone. This amount is in accordance with the BIDMC Committee on Clinical 
Investigations (CCI) Blood Volume Safety Guidelines.  
 
The CRC staff will centrifuge the blood samples for the complete blood count, 
hepatic function panel, basic metabolic panel, and sex hormones for 15 min at 
2000x g and 4°C between 15 and 30 min after collection. They will aliquot the 
plasma and serum in labeled 250 μl cryovials and store the samples at -80°C in 
CRC freezers. The CRC will send blood samples to Quest Diagnostics. The safety 
measurements will be conducted within 72 hours of collection. At the end of the 
study, they will send frozen samples from each visit to Quest Diagnostics for 
analysis of sex hormones. The CRC nurses will conduct the blood draws, specimen 
processing, and transfer to Quest Diagnostics in accordance with the CRC’s 
established protocols to maintain the quality of the specimens and to protect the 
privacy of the participants. 
 
Safety and Adherence: A member of the research team will call participants once 
per week to ask about any changes in health, to remind the participant to complete 
the weekly online questionnaire about lifestyle factors, and to address any questions 
that they may have about their participation in the study. A safety monitor will 
oversee patient safety by regularly monitoring participants’ vital sign and body 
measurements from clinic visits, lab results for liver function, complete blood 
count, and triglycerides and responses to questions from the weekly check-in calls 
about any changes in health, and they will follow up with any participant whose 
results are concerning.  
 
We will assess adherence by asking participants to return unused drinks so that we 
can measure how many drinks the participant consumed, at least from the provided 
drinks. Throughout the ten weeks of the trial, participants will complete weekly 
REDCap online questionnaires about lifestyle factors over the prior week. We will 
also ask participants about their alcohol intake. Depending on participant preference 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
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and feasibility, participants may report daily alcohol intake using the REDCap 
alcohol timeline follow-back assessment or they may opt to respond to a daily 
REDCap-secured survey that will be texted to them every evening. If participants 
report more than the assigned amount of wine during any study visit including the 
final visit, on a questionnaire, or during a phone call with study staff, Dr. Kenneth 
Mukamal will speak with them to determine if any evidence of alcohol use disorder 
or at-risk drinking is present, and all such participants will be referred for 
counseling. Those with no such evidence of problem drinking will remain in the 
study with continued monitoring. 
 
As an objective marker of alcohol adherence, we will pool some of the remaining 
blood samples across participants. After the sex hormone analyses are complete, the 
staff at the Brigham Research Assay Core who conducted the sex hormone analyses 
will one pooled sample from several participants following the wine phase and one 
pooled sample from several participants following the grape juice phase. We will 
send the two samples to Quest Diagnostics to estimate average phosphatidyl ethanol 
levels as an objective marker of adherence to the study protocol—the average 
phosphatidyl ethanol levels by treatment period across several individuals, with no 
individual results for each participant. The purpose is to estimate an objective 
marker of alcohol adherence, and not to test any new scientific hypotheses. We plan 
to report the average phosphatidyl ethanol levels in our findings on the study. 
 
To minimize risk, we have established clear and conservative entry criteria for 
interested participants. In particular, we require that all participants are current 
drinkers and that they typically consume at least one alcoholic drink per week but 
no more than two servings per day. This level, and the intervention dose of one 
drink per day, are explicitly within the limits of consumption for women diagnosed 
with breast cancer established by the American Society of Clinical Oncology. 
 
We will establish a formal safety monitor. This role may be filled by Dr. Steven 
Come or by a breast cancer specialist to whom he may delegate this role. The safety 
monitor will oversee patient safety by regularly monitoring participants’ lab results 
and responses to questions from the weekly check-in calls about any changes in 
health. They will assess the severity, expectedness, and relationship to the 
intervention for any self-reported symptoms or lab results and document adverse 
events. In addition, we will set up an independent data safety and monitoring board 
(DSMB) that will meet every 6 months to evaluate the safety and utility of 
continuing the pilot trial. 
 
If a participant experiences an adverse event, she will be directed to her treating 
oncologist. We will also notify the IRB, as appropriate (see section 12).  
 
We aim to assure data quality and protect the confidentiality of participant data by 
using REDCap electronic data capture tools. REDCap (Research Electronic Data 
Capture) is a secure, web-based application designed to support data capture for 
research studies.  

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We are submitting drafts of the study materials with this application for protocol 
approval, and we will convert these data collection tools to forms in the REDCap 
database. 
 
Screening Eligibility Checklist: The study staff will complete this measure with the 
participant during the screening visit and by reviewing medical records. This 
assessment includes the Alcohol Use Disorders Identification Test (AUDIT). At the 
screening visit, we will also collect contact information. 
 
Clinical Research Center Visit form: We will collect information about 
anthropomorphic data, blood samples, and responses to questions about medical 
history, lifestyle factors, alcohol intake, and changes in medications during the 
study. 
 
Weekly Check-In Call: The study staff will call participants once per week and ask 
them if they “had any reason to speak to or visit your health practitioner since we 
last spoke?” If the participant responds that there have been reasons to seek care, 
the study staff will ask for details. The study staff will also ask if “there any other 
changes to your health that you want us to know about?” and if the participant 
reports any changes, the study staff will ask for details. This information will be 
relayed for the safety monitor to review in the secure REDCap system. We will use 
the structure of the alcohol timeline follow-back survey to assess daily alcohol and 
grape juice intake since the prior check-in call. We will ask participants to record 
their daily intake on their paper diary that we gave them at Visit 1. 
 
Weekly REDCap Survey: Participants will complete an online weekly survey 
through the REDCap system. If they would prefer to complete this survey by phone, 
a member of the study staff will conduct this survey as an interview by phone and 
enter the data into REDCap on the participant’s behalf. The survey also includes the 
short version of the Centre for Epidemiological Studies Depression Scale (CES-D 
10), a Pain Intensity Scale using a visual analog scale to rate overall pain from 0 to 
100, and in two of the weekly assessments, participants will complete the Pittsburgh 
Sleep Quality Index (PSQI) about their sleep quality over the prior month. 
 
As indicated in the table of assessment times below, we will collect information 
about eligibility at the screening visit, and at visits 1, 2, 3, and 4, we will collect 
information about body measurements, vital signs, blood samples, and alcohol 
intake. In the weekly questionnaires, participants will provide information about 
alcohol intake, lifestyle factors, and any concerns. We will schedule blood draws 
for time windows of up to ±4 days of the end of the prior washout or drinking 
period. If the visit is delayed for up to four days, we will ask participants to 
continue the protocol (washout, white wine, or white grape juice) for the additional 
days. Similarly, we will schedule weekly calls for up to 4 days before or 4 days 
after the target schedule date. 
 

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Screening 
Washout 1 
Washout 1 
Visit 1 
Drinking Period 
 
Drinking Period 
1 
Drinking Period 
 
Visit 2 
Washout 2 
Washout 2 
Visit 3 
Drinking Period 
2 
Drinking Period 
 
Drinking Period 
2 
Visit 4 
# Assessments 
  
Study Day 0  1-7  8-14 15  15-21 
 22-28 
 29-35 36  36-42 
 43-49 50  51-57 
 58-64 
 65-71 72 
  
 
Window Allowance (Days)  ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 
 
Type of Visit 
C
l
in
ic Phone 
Phone C
l
in
ic Phone 
Phone 
Phone C
l
in
ic Phone 
Phone C
l
in
ic Phone 
Phone 
Phone C
l
in
ic 
 
Payment  
 
 $20  
 
 $30  
 $30  
 
 $50 
Admin, Body Measurements, and Vitals 
                                
  Consent, contact information  
X                             1 
 
Eligibility: e.g., Alcohol use Disorders 
Identification Test (AUDIT) and hepatic panel if 
none in the past 12 months* 
X               1 
  Randomization 
      X                       1 
  Verification of consent and documentation 
      X       X     X       X 4 
  Height 
      X                       1 
  Weight, waist circumference 
      X       X     X       X 4 
  Vital signs- blood pressure, heart rate 
      X       X     X       X 4 
  Distribute drink 
      X             X         2 
  Measure leftover drink 
              X             X 2 
  Pay participant, reimburse parking 
      X       X     X       X 4 
Blood Draw 
                                
  Hepatic panel  
 *     X       X     X       X 4 
 Complete blood count with differential 
  
    X       X     X       X 4 
  Basic metabolic panel (fasting) 
  
    X       
                1 
  Lipid panel 
  
    
        X             X 2 
 Estradiol and estrone 
  
    X       X     X       X 4 
  Sex hormone binding globulin (SHBG) 
  
    X       X     X       X 4 
  Dehydroepiandrosterone sulfate (DHEAS) 
  
    X       X     X       X 4 
  Testosterone 
  
    X       X     X       X 4 
Weekly Call 
                                
  Health events 
  X X   X X X   X X   X X X   10 
  Other health changes 
  X X   X X X   X X   X X X   10 
 Alcohol and grape juice timeline follow-back 
  X X   X X X   X X   X X X   10 
Weekly REDCap Questionnaires 
                                
  Pittsburgh Sleep Quality Index (PSQI) 
            X             X   2 
  Depressive Symptoms (CES-D-10) 
  X X   X X X   X X   X X X   10 
  Overall pain (visual analog scale) 
  X X   X X X   X X   X X X   10 
  Open text-any questions, concerns, comments   X X   X X X   X X   X X X   10 

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10.0 Data and Specimen Banking* 
We will store the blood samples for sex hormone levels from each study 
visit in a −80 °C freezer at BIDMC until all participants complete the study. 
Only members of the study staff will have access to the specimens. 
 
Each specimen will be labeled with a study identifier. The crosswalk file 
linking these subject identifiers to participants’ private health information 
will be stored in separate computer files with password protection, and 
results will be presented only in aggregate.  
 
Once the trial is complete, we will adhere to all required regulations 
regarding data dissemination. As outlined in the Notice of NIAAA Data-
Sharing Policy for Human Subjects Grants Research Funded by the National 
Institute on Alcohol Abuse and Alcoholism 
(https://grants.nih.gov/grants/guide/notice-files/NOT-AA-18-010.html), 
NIAAA uses an established informatics infrastructure, hosted and managed 
by the National Institute of Mental Health (NIMH) to enable the sharing and 
use of data collected from human subjects. The NIMH Data Archive 
(https://data-archive.nimh.nih.gov/) stores and disseminates data from 
funded clinical trials, and we will work with the NDA to create a compatible 
data structure and appropriately tagged fields and strip all identifiers from 
submitted datasets. We anticipate that data submitted to the NDA will 
become available to the general public 2 years after the completion of the 
proposed K01 award, as specified by NIAAA. Because of the limited size 
(20 subjects, single-center) of the proposed trial, all costs associated with 
data submission will be subsumed by effort allocated to the Principal 
Investigator and by budgeted costs at the BIDMC Clinical Research Center. 
 
11.0 Data Management* and Confidentiality 
We will present descriptive statistics on the proportion of people screened 
who were eligible and ineligible, and the number randomized. We will 
describe the health characteristics and self-reported adherence of the 
completers and non-completers based on the available data. 
We will construct linear mixed models to examine within-person changes in 
levels of estradiol, testosterone, DHEAS, and SHBG from grape juice to 
white wine, including a random subject intercept and fixed effects for 
treatment and sequence. We will assess the potential for a carryover effect 
by evaluating a cross-product term for treatment and sequence. We will use 
a logarithmic transformation for skewed distributions of the sex hormone 
levels. 
 

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We will use Markov Chain Monte Carlo (MCMC) multiple imputation. For 
each treatment arm, we will use the SAS “proc mi” procedure to generate 10 
multiply imputed datasets that incorporate appropriate variability across the 
imputations. We will use the SAS “proc mianalyze” procedure to combine 
the results from the imputed data sets to properly reflect the uncertainty due 
to missing values.  
 
Our primary analysis will use an intention-to-treat (ITT) approach, 
classifying participants according to their assigned treatment arms 
regardless of adherence to study protocol. In a sensitivity analysis, we will 
use a per-protocol approach in which a participant’s follow-up will be 
terminated at the time, if any, at which they cease to follow the protocol, and 
we will adjust for pre-randomization and post-randomization factors that 
may predict adherence. 
 
Our primary endpoint is free estradiol (estradiol divided by SHBG). We should 
have excellent power to assess effects of alcohol on DHEAS but reasonable power 
to detect effects on estrone sulfate, although, as a pilot study with an intentional 
goal of training and career development, power is but one dimension on which to 
evaluate the merits of the trial. We have used standard formulae to estimate the 
minimum detectable difference for 2-period crossover trials 
(http://hedwig.mgh.harvard.edu/sample_size/js/js_crossover_quant.html). Using the 
4-week results of a similar crossover trial of alcohol on changes in estrone sulfate 
and DHEAS, and using the dosage of 15 gm/day that most closely approximates the 
dosage proposed in this application, we can estimate the proportional changes 
anticipated with varying degrees of power, as shown below at a two-sided 0.05 
significance level. Based upon data presented in that trial, we estimate the SD of 
within-person differences to be 42% for estrone sulfate and 13% for DHEAS. 
 
Power 
Minimum Detectable Difference 
Estrone sulfate (ng/dl) 
DHEAS (ng/dl) 
50% 
19% 
6% 
80% 
28% 
9% 
90% 
32% 
10% 
 
For comparison, the increases in estrone sulfate in previous trials of alcohol were 
15-21% in a trial of premenopausal women and 7-22% in a trial of 
postmenopausal women.  
 
The comparable effects on DHEAS were 4-7% and 5-9%. Thus, we appear to 
have adequate power to detect effects of the expected size from previous 
crossover trials. Moreover, we have particularly strong power to exclude virtually 
all clinically significant increases (e.g., increases of 10% or larger) in DHEAS. 

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Our results would also provide all necessary information to power a more 
definitive trial of estrone and other estrogens. 
 
We aim to assure data quality and protect the confidentiality of participant data. We 
will keep all electronic data behind secure firewalls and all paper forms in locked 
files accessible by authorized personnel only. Subject identifiers will be stored in 
separate computer files with password protection, and results will be presented only 
in aggregate. We will use REDCap (Research Electronic Data Capture) tools hosted 
at BIDMC. REDCap is a secure, web-based application designed to support data 
capture for research studies. REDCap provides advanced de-identification options 
that can be used when exporting data, such as removing known identifier fields, 
removing invalidated text fields, notes fields, or date fields, date shifting, and 
hashing of the record names. It also includes a randomization module. REDCap 
utilizes a third-party vendor, Twilio, to send an SMS message with a REDCap 
survey link.  Subjects can click on the link and be directed to a REDCap survey on 
their phone. 
 
During all phases of a study, we aim to ensure that all data are carefully 
measured and recorded. We will use prepared phone scripts for recruitment, 
appointment reminders, and weekly check-in calls to provide information 
about the study and its procedures and to obtain study responses in as 
consistent a manner as possible. Our manual of operations will include 
details on where to obtain patient information, how to record the data, how 
to classify and report adverse events, and whom to contact with questions so 
that all members of the study team record information in a consistent 
manner throughout the trial.  
All study staff will be trained and certified in privacy protection, the Health 
Insurance Portability and Accountability Act (HIPAA), and the ethical 
conduct of clinical research. Study team members will meet regularly for 
study training and to make sure that all questions are asked similarly.  
We will check the consent form and any paper forms for completeness, and 
double-enter the data to minimize errors.  
Our REDCap database will have data validation rules and required fields to 
minimize the risk of incorrect and missing information. To ensure that the 
data are accurate and complete, we will create study-specific flow sheets for 
each study visit to ensure that the data collected is consistent at each study 
visit. Prior to initiating the study, the PI or her designee will hold a session 
to train Clinical Research Center staff in the conduct of the study. The study 
team will enter data in real time directly into the REDCap database rather 
than completing paper forms and manual data entry. This includes baseline 
information such as inclusion and exclusion criteria, randomization arm, 
measures of adherence to the drinking and washout periods, visit data such 
as vital signs and blood draw details, medication changes, adverse events, 
and other measures.  

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We will use standardized procedures for measuring vital signs and obtaining 
blood samples, and we will use validated measures for assessing the 
frequency of alcohol intake to increase the likelihood that the data is 
accurate and complete.  
We will call participants once a week to make sure that they have access to 
their drinks, that they are adhering to the protocol, and that they complete 
the study assessments. 
Quest Diagnostics will conduct specimen analyses for safety markers 
(hepatic panel, complete blood count with differential, fasting basic 
metabolic panel, and lipid panel). We will follow standard laboratory 
practices regarding sample chain of custody and sample confidentiality. This 
lab is approved by the Harvard Catalyst organization, and it is used by the 
BIDMC Clinical Research Center because they provide high-quality 
research and clinical data.  
 
We will label all specimens with the date and time of the blood draw and two 
subject identifiers using labels from the Quest Diagnostics ordering system to 
minimize the risk of mislabeling specimens. We will send the samples for safety 
monitoring assays to Quest Diagnostics within 72 hours of collection. Prior to 
transport to the Quest Diagnostics laboratory, samples will be processed according 
to the laboratory guidelines for sample submission.  
 
We will obtain laboratory results about the safety measures from the Quest eResults 
system and manually enter the data into the study database. We will retain paper 
copies of the reports and periodically conduct audits to compare the entered data 
with the paper copies to ensure that it was accurately entered in the study database. 
 
The Brigham Research Assay Core (BRAC) will conduct specimen analyses for sex 
hormones. We will centrifuge the samples for sex hormone assays and freeze the 
serum in aliquots at -80°C. At the end of the study, we will bring the samples to the 
BRAC. They will use liquid chromatography–mass spectrometry to measure 
estradiol, estrone, and testosterone, and they will use chemiluminescence to 
measure sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate 
(DHEAS). We will follow their sampling, storage, and transport procedures.  
 
We will obtain laboratory results about the sex hormone measures from the 
Freezerworks database on the BRAC web portal system and manually enter the data 
into the study database. We will retain paper copies of the reports and periodically 
conduct audits to compare the entered data with the paper copies to ensure that it 
was accurately entered in the study database. 
 
 
Only members of the research team, including the CRC nurses, will have access to 
the data and specimens. Quest Diagnostics will transmit results through their secure 

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eResults system with study-specific account access. We will download results and 
enter the data into our study-specific REDCap database.  
 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
 
We will follow the NIAAA guidelines for administration of alcohol, including 
attention to informed consent; selecting participants that have no known increased 
risk of alcohol dependence; great attention to confidentiality; restriction to 
participants who regularly consume alcohol rather than alcohol-naïve individuals; 
exclusion of pregnant women; low alcohol exposure for the intervention period of 3 
weeks; access to medical backup services; and compensation for participation. 
 
Dr. Mukamal, a practicing primary care internist, Dr. Steven Come, an oncology 
internist, or an oncology internist identified by Dr. Come will oversee data safety. 
They will monitor laboratory results from the scheduled visits on a real-time basis for 
all participants. They will ensure comprehensive monitoring and entry of all safety-
related data in the REDCap electronic research management system, distinguishing 
between serious adverse events, non-serious adverse events, and unanticipated 
problems following the BIDMC’s IRB guidelines. The study team will meet every 
month to discuss the ongoing health and safety of participants. 
 
At all clinic visits, we will measure vital signs and body measurements. A member of 
the research team will call participants once per week to ask about any reasons to 
speak to or meet with a health practitioner and any other health changes. At all visits 
and on all weekly calls, we will encourage participants to contact us about any health 
concerns or questions. 
 
We will also obtain lab assays for a hepatic panel, lipid panel, and complete blood 
count. We will discontinue enrollment and immediately refer for treatment any 
participant who  
• Develops liver function test abnormalities greater than 2X the upper limit of 
normal or 
• Experiences 15% change in their white blood count, hemoglobin level, or 
platelet count that results in values outside the normal range or 
• Experiences a doubling of their triglyceride levels that results in values 
outside the normal range 
following the three weeks of consuming white wine. 
Participants who report any excess use of their assigned beverage per week will 
receive additional intensive surveillance by telephone, and we will discontinue 
enrollment if excessive alcohol use persists.  
 
If participants report more than the assigned amount of wine during any study visit 
including the final visit, on a questionnaire, or during a phone call with study staff, 
Dr. Kenneth Mukamal will speak with them to determine if any evidence of alcohol 
use disorder or at-risk drinking is present. If there is evidence of problem drinking, 
they will be immediately referred for treatment. Addiction specialists, including 

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psychopharmacologists and clinical social workers, practice within the Healthcare 
Associates multidisciplinary clinic and are available on-call at all times. 
 
We will report adverse events as follows:  
1. Unexpected fatal or life-threatening adverse events will be reported to the 
BIDMC institutional review board (the Committee on Clinical Investigations - 
CCI) and the BIDMC General Clinical Research Center (GCRC) Research 
Subject Safety Office (RSSO) by telephone or in person within one business 
day of notification, and followed by a formal written report within seven 
calendar days.  
2. All other expected and unexpected serious adverse events will be reported 
to the CCI and the GCRC RSSO within seven calendar days.  
3. We will also provide the GCRC RSSO with an annual summary of adverse 
events (including anticipated, non-serious adverse events), delineated by 
category and number in addition to that provided to the CCI.  
 
Any serious adverse event will lead to a cessation of enrollment until the 
relationship between the adverse event and the study conduct is determined. 
 
The study team will meet at least once per month to discuss the information 
collected from the CRC visits, lab results, weekly calls and REDCap surveys, and 
any calls from participants about other concerns or health changes. We will discuss 
the safety of trial enrollment and any concerns and whether we should propose any 
changes to the protocol. 
 
In addition to this intense safety oversight, we will develop an independent Data 
and Safety Monitoring Board (DSMB) comprised of a general internist or 
oncologist with expertise in clinical trial conduct, an alcohol expert (who may also 
be a physician), and a biostatistician. The DSMB will meet every 6 months during 
the trial and more frequently as needed. We will notify the DSMB immediately if 
any unexpected life-threatening or fatal adverse events occur. They will provide 
reports after each meeting outlining the safety of the trial and delineate any plans 
for interruption or discontinuation of the trial.  
 
The content of the Data and Safety Monitoring Reports will include details such as 
a. Number of participants screened, reasons potential participants excluded, the 
number enrolled 
b. Frequency, mean, min/max of all laboratory safety assays, e.g., elevations in liver 
function tests, severe neuropsychiatric disturbances, or changes in vital signs 
c. Quality and completeness of the study data: frequency of missing or erroneous 
data, and frequency of outliers 
d. Safety data by treatment period, including frequency of adverse events, serious 
adverse events, and any data that allows for comparisons of safety among alcohol 
and non-alcohol dietary periods, e.g., clinical laboratory data, treatment retention, 
and reasons for participant dropout.  

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e. Individual participant data will be available for DSMB review as needed. In the 
assessment of serious adverse events, the DSMB will review each case, including 
treatment group assignment. 
 
The DSMB will stop the trial if there is evidence of any of the following conditions: 
a. Clear evidence of harm 
b. No likelihood of demonstrating treatment benefit (futility) 
c. Overwhelming evidence of the benefit of treatment 
 
We have no reason to anticipate that alcohol is beneficial for sex hormone levels. 
Rather, we are testing whether the constant use of aromatase inhibitor therapy 
throughout study enrollment lowers the impact of alcohol consumption on within-
person changes in sex hormone levels. If the results of the lab results indicate that the 
low alcohol intake is harmful as defined by the DSMB, the DSMB will stop the trial.  
 
13.0 Withdrawal of Subjects* 
We may decide to terminate a subject’s participation in the trial without 
regard to the subject’s consent if  
a. there is a concern that the alcohol intake is causing an unacceptable 
level of risk 
b. the subject is not adhering to the study protocol 
c. the subject is not meeting at arranged times despite repeated attempts, 
or because  
d. the inclusion/exclusion criteria are no longer met (e.g. a new surgery is 
scheduled to take place during trial participation or a new medication 
is initiated and alcohol is contraindicated to its use).  
 
We will reassure participants that they are free to discontinue participation in the 
study at any time for any reason without fear of penalty or loss of medical care or 
loss of any benefits to which they may otherwise be entitled. In the event of early 
termination/withdrawal from the study, a member of the study staff will conduct an 
exit interview to identify the reasons for terminating participation, and we will 
recommend that the participant follow up with their health care providers if they 
report and medical or psychological reasons for discontinuing participation. We will 
document the date of study withdrawal, whether the withdrawal of the subject 
resulted from a decision by the subject or by the investigator, and the reasons for 
the withdrawal. If appropriate, we will request the return of any remaining 
beverages and provide payment for any visits completed on the day of termination. 
 
If a participant chooses to withdraw from the study, the data collected up to the time 
of withdrawal will continue to be used, but the participant will no longer be 
contacted and no further data will be collected. 
 
14.0 Risks to Subjects* 
Because alcohol will only be provided for three weeks to participants, we do not 
anticipate any measurable or clinically meaningful increase in the potential long-

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term risks related to alcohol consumption, including any measurable risk in chronic 
disease. The potential risks to study participants from use of alcohol for three weeks 
include risks related to temporary sedation (such as the use of machinery 
immediately after drinking), gastrointestinal upset, flushing (in cases of genetic 
intolerance to alcohol or use of specific medications), and a potential worsening of 
liver disease among people with pre-existing liver disease. In addition, alcohol is an 
addictive substance, although the risk of precipitating alcohol misuse among 
women already consuming alcohol safely is likely low. For both arms, the assigned 
beverage contains ~120 calories and can cause weight gain if not balanced by 
decreases in the caloric content of the diet.  
 
The only other risks related to this study are procedural and include discomfort or 
anxiety answering questions about medical history and pain and temporary slight 
discoloration of the skin after blood draws.  
 
Specifically, potential risks associated with study participation include anxiety 
related to completing the questionnaires, temporary discomfort and slight 
discoloration of the skin after blood draws, and feeling ill after drinking a serving of 
wine or grape juice. However, all participants will be postmenopausal women with 
estrogen receptor-positive (ER+) breast cancer who regularly consume alcohol, so 
these risks seem less likely than if we were recruiting from the general population. 
There is a potential risk of psychological harm due to inadvertent disclosure of 
medical information. However, we will record information behind a secure firewall 
using the REDCap system. 
 
Completing the online questionnaires, phone check-ins and interviews could lead to 
the unforeseeable risk of a breach of confidentiality if someone other than the 
research team obtained access to the data. However, the screening and enrollment 
lists, lab results, interview responses, and questionnaires will all be entered and 
stored in the secure REDCap system with features to export de-identified datasets 
for analysis. The consent forms will include participant names, but the signed forms 
will be stored in a locked cabinet. 
 
Aromatase inhibitors are only prescribed to women who are naturally or artificially 
(e.g. hysterectomy) postmenopausal. Therefore, no women will join the study 
pregnant or become pregnant during their participation in the study. 
 
There are no known risks to others who are not subjects. 
 
15.0 Potential Benefits to Subjects* 
As we will indicate in the informed consent form, there are no clinical benefits to 
participation. 
 
As we indicated in the informed consent form, there are no direct benefits to 
participation. 

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16.0 Vulnerable Populations* 
Not Applicable. We will not include pregnant women, prisoners, children, or 
impaired adults. 
 
17.0 Community-Based Participatory Research* 
Not Applicable. This trial does not involve community-based participatory 
research. 
 
18.0 Sharing of Results with Subjects* 
We will assure participants that the line of communication is open and provide 
participants with the research team’s contact information should they have follow-
up questions. When the study first becomes available in its entirety through public 
access, we will contact participants by phone or email, based on their preference, to 
inform them about how they can look for published study results, and we will share 
the study’s official name and Protocol ID number so they may search public 
databases. 
 
 
19.0 Setting 
 
Screening visits will take place at the Beth Israel Medical Center BreastCare 
Center: 
 
Joseph M. and Thelma Linsey BreastCare Center 
330 Brookline Avenue 
Shapiro Clinical Center, 4th Floor 
Boston, MA 02215 
 
Subsequent visits will take place at the Beth Israel Deaconess Medical Center 
Clinical Research Center, located in the Clinical Research Center on East 
Campus: 
 
Clinical Research Center 
330 Brookline Avenue 
Gryzmish Building, 8th Floor 
Boston, MA 02115 
 
After the blood samples are prepared at the clinical research center, safety 
measures will be sent for analysis to: 
 
Quest Diagnostics LLC 
200 Forest Street, 3rd Floor, Suite B 
Marlborough, MA 01752-3023 
 

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Sex hormone blood samples will be prepared at the clinical research center and 
stored at BIDMC. At the end of the study, these frozen samples will be sent for 
analysis to: 
 
Brigham Research Assay Core 
221 Longwood Avenue 
RFB Room 477 
Boston, MA 02115 
 
 
There is no community advisory board for this research. This is a single-site pilot 
trial, so no study visits for this research will take place outside of this 
organization. 
 
20.0 Resources Available 
All members of the study team have experience conducting clinical trials and have 
training in the safety, privacy, and integrity laws about the conduct of clinical 
research. 
Dr. Kenneth J Mukamal is the primary investigator of this trial and co-
mentor of the NIH/NIAAA K01 career development award funding this 
study (K01AA027831).  He is Associate Professor of Medicine at Beth 
Israel Deaconess Medical Center (BIDMC). His primary research interests 
are investigating the role of dietary and lifestyle factors—particularly 
alcohol intake—on the incidence and prognosis of cardiovascular and 
neurovascular disease. As a general internist and clinical investigator, he has 
vast experience conducting studies on the health effects of alcohol. He has 
conducted a randomized trial of alcohol among patients at high 
cardiovascular risk at BIDMC that informs the design and conduct of this 
trial. Dr. Mukamal served as a member of the BIDMC IRB for 
approximately fifteen years and he is attuned to the importance of safety and 
confidentiality concerns. 
Dr. Steven Come is Associate Professor of Medicine at Harvard Medical 
School and a treating physician at the Beth Israel Deaconess Medical 
Center’s Breast Cancer Program. He is a collaborator on the career 
development award. As a physician providing care to breast cancer patients 
and a clinical researcher of chemotherapy, Dr. Come will be the liaison 
between the BreastCare Center team and the study staff to identify eligible 
women with estrogen receptor-positive (ER+) breast cancer from the 
BreastCare Center who may be interested in participating and to monitor the 
safety of the trial participants. Dr. Come may delegate some of these 
recruitment and monitoring responsibilities to other oncologists at the 
BreastCare Center, such as Dr. Jaymin M. Patel. 
Dr. Julie E. Buring is Professor of Medicine at Brigham and Women’s 
Hospital (BWH) and Professor of Epidemiology at the Harvard T.H. Chan 
School of Public Health. She is the primary mentor on the career 

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development award that is funding this study (K01AA027831). Dr. Buring 
has been involved in the design, conduct, analysis, and interpretation of 
several randomized clinical trials and large-scale cohort studies. Dr. Buring 
serves as Chair of the Institutional Review Board at Harvard Medical 
School, and she is both familiar with and dedicated to the responsible 
conduct of research. 
Dr. Elizabeth Mostofsky is the NIAAA K01 career development awardee for the 
grant that is funding this trial. She has been involved in conducting small clinical 
trials and will devote a large proportion of her time to the design and conduct of this 
trial with close mentorship from Drs. Buring, Mukamal, and Come. This pilot study 
is funded by very limited project funds from Dr. Mostofsky’s K01 award and 
comprises a total of 20 women – a small enough total to be readily completed at a 
single center.  Dr. Mostofsky, a research collaborator at BIDMC, will conduct 
recruitment herself at the BI oncology clinics.  As a result, expansion beyond 
BIDMC is not currently feasible on the project’s NIH-funded budget. 
 
After obtaining IRB approval, we will work with the CRC to finalize the plans to 
purchase, store, and transfer the white wine and white grape juice to participants. 
All alcohol and grape juice transfers, blood draws, and physical exams will take 
place with oversight of the experienced staff at the BIDMC Clinical Research 
Center with frequent consultation with Drs. Buring, Mukamal, and Come.  
 
BIDMC follows over 5,000 women with breast cancer who account for over 8,000 
visits yearly, of whom over 3,500 are likely to be ER+, of whom a vast majority are 
likely to be taking an aromatase inhibitor and hence potentially eligible for our trial. 
By working closely with oncologists in the BIDMC BreastCare Center, we are 
highly likely to identify, recruit, and enroll 20 women to complete the study. If we 
face challenges with recruitment, we will apply for an IRB amendment to broaden 
our recruitment to other audiences. Since the trial is only 10 weeks and participants 
complete both treatment arms that involve low levels of consumption, it is feasible 
to complete this trial in the timeline proposed. 
 
The proposed trial is a primary aim of a career development award funded by the 
National Institute on Alcohol Abuse and Alcoholism (K01AA027831), which 
provides 80% of my effort. Therefore, completing this trial is of utmost importance, 
and it will be Dr. Mostofsky’s focus during the timeline of the trial.  
 
We aim to primarily recruit participants from the Joseph M. and Thelma Linsey 
BreastCare Center. The oncology team includes six attending physicians and three 
nurse practitioners who provide care to more than 4,000 patients per year. 
 
The BIDMC Clinical Research Center is located on the BIDMC East Campus. The 
staff will provide their experience and assistance with advertising the study and 
recruiting participants, and their licensed nursing staff will conduct the weight 

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measurements, storage and distribution of the wine and grape juice, the blood 
draws, the blood sample preparation for freezing, and shipment of the blood 
samples to Quest Laboratories. 
 
Dr. Kenneth J. Mukamal is a general internist and clinical investigator at BIDMC 
with extensive experience conducting observational and interventional studies on 
the effects of alcohol consumption. Dr. Steven Come is an oncologist in the 
BIDMC BreastCare Center where we will primarily recruit participants for this 
trial. Dr. Mukamal, Dr. Come, and any physician to whom they delegate safety 
monitoring responsibilities will review the results of the safety measures and 
classify them according to severity, relation to the study intervention, and whether it 
had been expected or not.  
 
Before engaging with potential study participants, we will meet with staff members, 
from oncologists to CRC nurses and research assistants, to ensure that they are 
familiar with the study protocol and safety measures. As described in section 12.0, 
we have a formal plan to ensure that the study staff knows whom to contact with 
questions or concerns about safety or other protocol issues and how to contact a 
study physician if needed. 
 
21.0 Prior Approvals 
On December 17, 2021, we received notification from the FDA that our 
study does not require an IND. The letter is included in our application 
packet. 
 
22.0 Recruitment Methods 
We will present the trial protocol and eligibility criteria at a meeting for the six 
medical oncologists and three nurse practitioners who provide outpatient care at the 
BIDMC BreastCare Center and ask for their assistance to recruit patients from their 
practice who may be eligible and interested in participating in our trial.  
 
We will review medical records for patients in the BreastCare Center with 
upcoming appointments to confirm eligibility. We will notify the BreastCare Center 
health providers about their upcoming visits with potentially eligible patients so that 
they may target their recruitment efforts toward their patients who are potentially 
eligible to participate. 
  
The BreastCare Center health practitioners will describe our study to these patients 
and ask the patient if they are interested in being contacted to learn more about 
participation in the trial. If the patient agrees to be contacted and a study team 
member and the patient are available at that time, we will meet the participant at the 
BreastCare Center to discuss the study at that time. If the patient agrees to be 
contacted but is not available at that time, we will mail them an IRB-approved letter 

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with information about the study and contact information for them to speak to 
someone on the study team. If they contact us, we will arrange a screening visit. 
Otherwise, we will contact them within a week of receiving the letter to ask them if 
they have any questions and are interested in meeting for a screening visit. We will 
also place flyers and brochures in the BreastCare Center so that women who are 
interested in the study can reach out to us.  
 
This application includes the 
• Brochure for the BreastCare Center study staff, including the 
inclusion/exclusion criteria, a figure of the study design, and the 
study team contact information so that they can tell us about 
potentially eligible participants 
• Flyer for the BreastCare Center waiting room 
• Telephone Script for Recruitment  
• Invitation letter, including a study information sheet with frequently 
asked questions 
We will provide parking vouchers to participants who plan to drive to BIDMC. In 
addition, we will compensate participants for their time and effort at the end of each 
study visit, with a total of $130 for completing all 10 weeks of the study ($20 for 
Visit 1 (Baseline), $30 for Visit 2, $30 for Visit 3, and $50 for Visit 4). These levels 
of compensation are designed to provide some minimal compensation for the time 
and inconvenience of these visits without providing any undue incentive to join the 
study, a particularly important consideration in studies of alcohol. 
 
We will pay participants using a pre-paid debit card called ClinCard® that is 
administered by the company Greenphire to manage all payments associated with 
participation in study visits and travel related to participation in the study.  We will 
add the money to the card after each completed visit. Participants may use this card 
at any store that accepts credit cards, or they can use a bank machine to remove 
cash. However, there may be fees drawn against the balance of the card for cash 
withdrawals and inactivity.  
 
23.0 Local Number of Subjects 
We will screen and enroll participants until we have 20 participants who 
have completed the ten weeks of the study. 
 
BIDMC follows over 5,000 women with breast cancer who account for over 8,000 
visits yearly, of whom over 3,500 are likely to be ER+ and hence potentially 
eligible for our trial.  
 
We plan to contact as many as 100 participants to ensure that at least 20 women 
complete the study. This pilot study is funded by very limited project funds from 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
Page 26 of 29 
 
Dr. Mostofsky’s K01 award and comprises 20 women – a small enough total to be 
readily completed at a single center.   
 
 
 
 
24.0 Provisions to Protect the Privacy Interests of Subjects 
We will protect subjects’ privacy interests by keeping all data behind secure 
firewalls and in locked files accessible by authorized personnel only. We will 
record all questionnaire and interview responses and all anthropometric 
measurements, lab results, and study staff notes using REDCap (Research 
Electronic Data Capture). REDCap is a secure web application designed to support 
data capture for research studies. It includes features for HIPAA compliance 
including real-time data entry validation (e.g., for data types and range checks), a 
full audit trail, user-based privileges, de-identified data export mechanism to 
statistical packages, and integration with Beth Israel directories. Access to study 
data in REDCap will be restricted to the members of the study team with 
authentication through institutional credentials. 
 
Subject identifiers will be stored in separate computer files with password 
protection, and results will be presented only in aggregate. In addition, 
current/future employees involved with the proposed study routinely must agree not 
to disclose any information to which he or she might have access, regardless of his 
or her perception about its confidentiality, as part of annual training. All BIDMC 
employees also complete training in the responsible conduct of research.  
 
We will explain to potential participants that we are working closely with 
Dr. Come and other health practitioners from the BIDMC BreastCare Center 
to ensure their safety. All visits will take place in a private room, and we 
will remind them that they can stop participating at any time with no 
concern of this withdrawal affecting their clinical care. At all visits and 
phone calls, we will remind the participants that they can reach out to us at 
any time with questions or concerns. 
 
We are submitting a request for a waiver of HIPAA authorization to disclose 
protected health information for anyone recommended by the BreastCare Center 
oncologists and nurse practitioners. We will access the patient’s recent medical 
records to confirm their eligibility for this trial. The research team will access 
participant information through the REDCap database. This secured database will 
be hosted by BIDMC behind the firewall of will be the centralized source of all 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
Page 27 of 29 
 
study data and administrative details for the screening process and the enrollment 
and conduct of the trial. Only authorized members of the study team will be able to 
access this information, and they will not share their login credentials with other 
personnel working on the study.  
 
25.0 Compensation for Research-Related Injury 
 
The treating hospital will offer the care needed to treat injuries directly 
resulting from taking part in this research. These treatments may be billed to 
the participant or to their insurance company. There are no plans to pay the 
participant or to provide other compensation for the injury, such as lost 
wages or lost time from work. 
 
If the participant is injured as a direct result of participation in this study, the 
participant will be offered the necessary care to treat their injury. The 
participant or their insurance company will be billed for medical care and/or 
hospitalization related to this injury. The participant will be responsible for 
co-payments, deductibles, and co-insurance. There are no plans to pay the 
participant or to provide other compensation for the injury, such as lost 
wages or lost time from work. 
 
26.0 Economic Burden to Subjects 
There are no costs to participants for completing the study. We will provide 
white wine, white grape juice, and a measuring cup. We will also provide 
parking passes for participants who plan to drive to the Beth Israel Medical 
Center Clinical Research Center. 
 
27.0 Consent Process 
Once a potential participant meets with study staff at the BIDMC 
BreastCare Center, we will obtain and document written informed consent 
to complete the screening process and if eligible, to be randomized for the 
crossover trial. We will follow all guidelines described in the Standard 
Operating Procedures for Human Subjects Research (CON-100). We will 
make sure that the informed consent process is conducted by a member of 
the study team who is trained in human subject protections, trained on the 
protocol, and listed on the Delegation of Authority Log. 
We will conduct the consent process in a private room at the BreastCare 
Center to ensure participant privacy and to make sure that they feel 
comfortable asking questions. We will remind participants that they can stop 
participating at any time and for any reason, and cessation will not have any 
impact on their medical care in any way. After explaining the study, asking 
the participants to carefully review the consent form, and discussing any 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
Page 28 of 29 
 
questions that they may have, the patient will sign the informed consent 
form. The study team member will document the informed consent date and 
time and they will confirm that they explained the research to the 
participant, ensured that the patient understood the expectations of 
participating, and that the patient freely consented to participate. This 
process will take approximately 30 minutes. 
At each visit, the CRC staff will ask the participant whether they would like 
to continue to participate in the study.  
We will restrict inclusion to participants who can speak and understand 
English because we do not have sufficient funding to prepare materials and 
conduct visits in other languages, and we need to be sure to identify any 
health and safety concerns that may arise during the study. 
We are submitting an application for a partial waiver of HIPAA 
authorization to review medical records of potentially eligible BreastCare 
Center patients in order to confirm eligibility. At the screening visit, we will 
obtain written consent to complete the screening process and potentially 
enroll in the trial. 
 
This trial does not involve subjects who are not yet adults (infants, children, 
teenagers). 
This trial does not involve cognitively impaired adults. 
This trial does not involve adults unable to consent. 
 
28.0 Process to Document Consent in Writing 
Following policy #CON-100, we will obtain and document the informed 
consent of each woman who participates in the trial. A member of the study 
team who is trained in human subjects protections and trained on the 
protocol will make sure that the potential participant voluntarily confirms 
her willingness to participate in research, after having been informed of all 
aspects of the research that are relevant to her decision to participate. The 
trained research staff will meet with the prospective participant in a private 
room and discuss the IRB-approved informed consent document, and make 
sure that the person clearly understands the range of risks, the potential 
benefits, and the voluntary nature of participating in the research. The study 
staff will remind the potential participant that she has the right to decline 
participation and to withdraw from the research without negatively affecting 
their subsequent medical care in any way at any time after the research has 
begun.  
She will be given time to consider participating in the research and to ask 
questions. If the prospective participant chooses to participate, she will sign 
and date the informed consent document, and the person obtaining informed 

Effect of Light Alcohol Intake on Sex Hormone Levels among Postmenopausal Women with ER+ Breast Cancer on Aromatase Inhibitor 
Therapy: The Alcohol and Breast Cancer (ABC) Trial 
 
Page 29 of 29 
 
consent will also sign and date the document. We will provide a copy of the 
signed and dated document to the participant and we will retain the signed 
and dated document in a locked file cabinet. 
We will obtain written documentation of informed consent using the consent 
form submitted with this IRB application. 
This application includes a draft of our consent form for written consent to 
participate in the study, and the last page includes a checklist for ensuring 
that the informed consent process is conducted in accordance with policy 
#CON-100. 
 
29.0 Drugs or Devices 
This trial does not involve the administration of drugs or the use of any 
devices. Our application includes the FDA’s letter on December 17th, 2021 
confirming that an Investigational New Drug Application (IND) is not 
required for our study. 

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 1 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
Protocol Title:  Effect of Light Alcohol Intake on Sex Hormone Levels among 
Postmenopausal Women on Aromatase Inhibitor Therapy
DF/HCC Principal Investigator(s) / Institution(s):  Kenneth J Mukamal / Beth Israel 
Deaconess Medical Center
Main Consent
I
NTRODUCTION AND KEY INFORMATION
All research is voluntary.  It is your choice whether you take part in this research 
or not. If you decide to participate, please sign and date at the end of this form. 
We will give you a copy and you can refer to this consent form at any time.
The following is a short summary of this research study to help you decide 
whether you would like to be a part of this study.  More detailed information is 
provided later in this form. 
 
For purposes of this research, you will be referred to as a “participant.”  
1. Why am I being invited to take part in a research study?
You are invited to take part in in this research study, because you are a 
postmenopausal woman with estrogen receptor-positive (ER+) breast cancer 
who takes an aromatase inhibitor.
2. Why is this research being done? 
The purpose of this study is to assess whether light alcohol intake increases sex 
hormone levels in the presence of standard breast cancer therapy.
3. Who is supporting this research?
A grant from the National Institutes of Health (K01AA027831) is supporting this 
research by providing funds for the staffing, supplies, and participant payments.
4. What does this research study involve and how long will it last?
This research study involves 10 weeks of participation, including 3 weeks 
consuming one serving of white wine daily, 3 weeks consuming one serving of 
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 2 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
white grape juice daily, and 2 weeks of drinking neither alcohol nor grape juice 
before each of these 3-week drinking periods. 
 
The names of the study exposures involved in this study are:
White wine
White grape juice
The research study procedures include one screening visit to obtain informed 
consent, four study visits with blood draws, and ten weekly phone calls and 
online questionnaires over the ten weeks of the study. Throughout the study, you 
should refrain from all alcohol and grape juice except your assigned drink and 
maintain your typical patterns of diet and activity throughout the study.
At the beginning of each 3-week drinking period, we will provide the white wine or 
white grape juice that you will need for the study. You will be asked to consume 
one serving per day of the study intervention (white wine) for three weeks and 
one serving per day of the study comparator (white grape juice) for three weeks, 
with each drinking period preceded by two weeks of no alcohol or grape juice 
consumption. You will not be followed after the ten-week study ends.
Alcohol consumption can affect coordination, motor skills, and cognition, i.e., the 
ability to think, judge, and reason. Driving after drinking alcohol increases the risk 
of vehicular accidents. After drinking alcohol, you should not drive, operate heavy 
machinery or engage in any activities that require you to be alert and/or respond 
quickly and you should not participate in activities that may be dangerous to 
yourself or to others. 
It is expected that about 20 women will take part in this research study. 
Information about you and your health is personal and private.  Generally, it 
cannot be obtained without your written permission. By signing this form, you are 
providing that permission, and your information may be obtained and used in 
accordance with this informed consent and as required or allowed by law. This 
means that researchers may obtain information regarding your past medical 
history, as well as specimens and samples from previous health care providers 
such as hospitals and labs.
5. What are the risks to participating in this study?
There are risks to taking part in any research study. We want to make sure you 
know about a few key risks right now. More detailed information is provided in the 
“What are the risks or discomforts of the research study?” section.
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Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 3 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
There is a risk that you could have side effects from the white wine.  
Some of the most common side effects that the study doctors know about are:
Feeling tired immediately after drinking white wine
Upset stomach after drinking white wine
Discomfort or anxiety answering questions
Pain and slight skin discoloration after blood draws
6. Will being in this study benefit me in any way?
We do not know if taking part in this study will benefit you. This study may help 
researchers learn information that could help people in the future and help 
postmenopausal women with estrogen receptor-positive (ER+) breast cancer 
make informed decisions about their alcohol intake.
7. What are my options?
Instead of being in this research study, you have other options which may include 
the following: 
Decide not to participate in this research study
Participate in another research study
If you choose not to participate, are not eligible to participate, or withdraw from 
this research study, this will not affect your present or future care and will not 
cause any penalty or loss of benefits to which you are otherwise entitled. 
We encourage you to take some time to think this over, to discuss it with other 
people and your primary doctor, and to ask questions at any time.
A. WHY IS THIS RESEARCH STUDY BEING DONE?
This research study is a pilot study, which is the first time investigators are 
examining the effect of light alcohol consumption on sex hormones among 
postmenopausal women with estrogen receptor-positive (ER+) breast cancer 
taking an aromatase inhibitor. In this experimental study, you will be asked to 
drink white wine and white grape juice, which are not consumed as the standard 
of care. The U.S. Food and Drug Administration (FDA) has not approved alcohol 
as a treatment for any disease.
In this research study,
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 4 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
We are studying the effect of 3 weeks of drinking one serving of white 
wine compared to 3 weeks of drinking one serving of white grape juice. 
We are conducting this study to understand whether drinking one serving 
of alcohol per day increases sex hormone levels such as estrogen while 
taking an aromatase inhibitor that aims to suppress levels of these 
hormones.
Alcohol intake raises sex hormone levels, however, it is unknown if that 
effect persists in postmenopausal women with estrogen receptor-positive 
(ER+) breast cancer taking an aromatase inhibitor. There have been no 
studies to examine alcohol’s effect on sex hormone levels among 
postmenopausal women with estrogen receptor-positive (ER+) breast 
cancer. These drugs are only prescribed to postmenopausal women who 
had estrogen receptor-positive (ER+) breast cancer, the subtype where 
alcohol has been found to increase breast cancer incidence. This 
information is needed for breast cancer survivors to make informed 
decisions about their alcohol intake and its potential effect on adjuvant AI 
therapy.
Previous studies have shown that alcohol increases sex hormone levels. 
Tamoxifen, a drug that blocks estrogen
's action on breast cells, dampened 
the association between self-reported alcohol over the past month or year 
and some hormones (DHEAS) but strengthened the association between 
alcohol and other hormones (SHBG). 
B. WHAT IS INVOLVED IN THE RESEARCH STUDY?
You will be “randomized” into one of the study drinking sequence groups: white 
wine followed by white grape juice or white grape juice followed by white wine. 
Randomization means that you are assigned one of these sequences by chance. 
It is like flipping a coin.  
You will have an equal chance of being placed in any of the following sequence 
groups: 
3 weeks of daily white wine followed by 3 weeks of daily white grape juice
3 weeks of daily white grape juice followed by 3 weeks of daily white wine
Before the research starts (screening visit):  
After signing this consent form, you will be asked to undergo some screening 
tests or procedures to find out if you can be in the research study.  Many of these 
tests and procedures are likely to be part of regular cancer care and may be 
done even if it turns out that you do not take part in the research study.  If you 
have had some of these tests or procedures recently, they may or may not have 
to be repeated.  
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Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 5 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
Medical history, which includes questions about your health, current 
medications, and lifestyle factors
Typical alcohol intake, including questions about how often you drink 
alcohol and how much you drink each time
Blood tests:  If you have not had liver function measured in the past 12 
months, the nurse will draw 10 mL (less than 1 tablespoon) of blood to 
measure your liver function levels.
If you do not meet the eligibility criteria, you will not be able to participate in this 
research study. If these assessments show that you are eligible to participate in 
the research study, you will be asked to refrain from drinking alcohol and grape 
juice for two weeks.  
Study Treatment Overview:
Drinking Periods:  Each study treatment cycle lasts 3 weeks during 
which time you will be taking the study drink (white wine or white grape 
juice) one time per day. There are two drinking periods during this 10-
week study.    
Washout Periods: Before both of the 3-week drinking periods, you will be 
asked to refrain from drinking all alcohol and grape juice.
Visit 1: During this visit, we will conduct a clinical exam and blood draw and we 
will give you the drink and measuring cup for you to use over the next three 
weeks.
This visit will involve the following:
Clinical Exams: You will have a physical exam (height, weight, waist 
circumference, blood pressure, and heart rate) and you will be asked 
questions about your general health and specific questions about any 
problems that you might be having and any medications you may be 
taking.
Blood tests:  We will obtain a blood sample after fasting for 12 hours. The 
nurse will draw 100 mL (approximately 7 tablespoons) of blood to monitor 
your health (liver function, blood count, basic metabolic panel) and to 
measure your sex hormone levels.
Visit 2: During this visit, we will conduct a clinical exam and blood draw and we 
will ask you to refrain from drinking alcohol and grape juice for the next two 
weeks.
This visit will involve the following:
Clinical Exams: You will have a physical exam (weight, waist 
circumference, blood pressure, and heart rate) and you will be asked 
questions about your general health and specific questions about any 
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 6 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
problems that you might be having and any medications you may be 
taking.
Blood tests:  The nurse will draw 90 mL (approximately 6 tablespoons) of 
blood to monitor your health (liver function and blood count) and to 
measure your sex hormone levels.
Visit 3: During this visit, we will conduct a clinical exam and blood draw and we 
will give you the drink for you to use over the next three weeks.
This visit will involve the following:
Clinical Exams: You will have a physical exam (weight, waist 
circumference, blood pressure, and heart rate) and you will be asked 
questions about your general health and specific questions about any 
problems that you might be having and any medications you may be 
taking.
Blood tests:  The nurse will draw 90 mL (approximately 6 tablespoons) of 
blood to monitor your health (liver function and blood count) and to 
measure your sex hormone levels.
Visit 4: During this visit, we will conduct a clinical exam and blood draw.
This visit will involve the following:
Clinical Exams: You will have a physical exam (weight, waist 
circumference, blood pressure, and heart rate) and you will be asked 
questions about your general health and specific questions about any 
problems that you might be having and any medications you may be 
taking.
Blood tests:  The nurse will draw 90 mL (approximately 6 tablespoons) of 
blood to monitor your health (liver function and blood count) and to 
measure your sex hormone levels.
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 7 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
Research Study Plan:
 
 
Screening
Washout 1
Washout 1
Visit 1
Drinking Period 
1
Drinking Period 
1
Drinking Period 
1
Visit 2
Washout 2
Washout 2
Visit 3
Drinking Period 
2
Drinking Period 
2
Drinking Period 
2
Visit 4
# Assessments
 
Study Day 0
 1-7 8-1415  15-
21
 22-
28
 29-
35
36  36-
42
 43-
49
50  51-
57
 58-
64
 65-
71
72
Window Allowance (Days)
±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4 ±4
Type of VisitClinicPhon
e
Phon
e
Clini
c
Phon
e
Phon
e
Phon
e
Clini
c
Phon
e
Phon
e
Clini
c
Phon
e
Phon
e
Phon
e
Clini
c
Payment
$20
$30
$30
$50
 
Admin, Body Measurements, and Vitals
                
 
Consent, , contact information 
X               1
Eligibility: e.g. Alcohol use Disorders Identification 
Test (AUDIT) and liver function test, if none in the 
past 12 months*
X
1
 
Randomization
   X            1
 
Verification of consent and documentation
   X    X   X    X 4
 
Height
   X            1
 
Weight, waist circumference
   X    X   X    X 4
 
Vital signs- blood pressure, heart rate
   X    X   X    X 4
 
Distribute drink
   X       X     2
 
Measure leftover drink
       X       X 2
 
Pay participant, reimburse parking
   X    X   X    X 4
Blood Draw
                
 
Hepatic panel 
 *   
X    
X   X    X 4
Complete blood count with differential
 
  
X    
X   X    X 4
 
Basic metabolic panel (fasting)
 
  
X    
        1
 
Lipid panel
 
  
    
X       X 2
 
Dehydroepiandrosterone sulfate (DHEAS)
 
  
X    
X   X    X 4
 
Sex hormone binding globulin (SHBG)
 
  
X    
X   X    X 4
 
Estradiol
 
  
X    
X   X    X 4
 
Testosterone
 
  
X    
X   X    X 4
Weekly Call
                
 
Health events
 X X  X X X  X X  X X X  10
 
Other health changes
 X X  X X X  X X  X X X  10
Weekly REDCap Questionnaires
                
 
Timeline follow-back (or daily REDCap text)
 
X X  X X X  X X  X X X  10
 
Pittsburgh Sleep Quality Index (PSQI)
      X       X  2
 
Depressive Symptoms (CES-D-6)
 X X  X X X  X X  X X X  10
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 8 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
 
Overall pain (visual analog scale)
 X X  X X X  X X  X X X  10
 
Open text-any questions, concerns, comments
 X X  X X X  X X  X X X  10
Planned Follow-up
We will not follow up with you after the 10-week study ends, but we will provide 
our contact information in case you have any questions after the study ends and 
we will ask for your permission to contact you to update you on the results of this 
study.
You can stop participating in the research study at any time, however, the FDA 
requires that any information collected up to the point of your withdrawal not be 
removed from the study.
C. WHAT ARE THE RISKS OR DISCOMFORTS OF THE RESEARCH STUDY?
There are risks to taking part in any research study. In this study, there may be 
side effects from the wine or grape juice, from giving blood samples, and from 
completing interviews. 
There is a great deal of variability among side effects and between individuals.  
In a research study, all of the risks or side effects may not be known before you 
start the study. You need to tell your doctor or a member of the study team 
immediately if you experience any side effects. 
Everyone in the research study will be watched carefully for side effects.  You will 
be monitored during the 10-week study to keep track of blood pressure, heart 
rate, liver function, blood count, and triglycerides. If you experience side effects, 
they may go away after you stop taking the wine or grape juice.  Some side 
effects can be mild, but other unexpected side effects can be long-lasting and 
may never go away.  Some may be life-threatening or fatal. 
Risks Associated with White Grape Juice and White Wine
Likely 
Feeling tired immediately after drinking white wine
Occasional 
After drinking white wine, you may experience the following side effects:
Upset stomach 
Turning red or "flushing" after drinking white wine (in cases of genetic 
intolerance to alcohol or use of specific medications)
Worsening of liver disease among people with pre-existing liver disease. 
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 9 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
For both the wine and grape juice drinking periods, the daily drinks contain 
approximately 120 calories and can cause weight gain if not balanced by 
decreases in the caloric content of the diet.
Rare 
Alcohol is an addictive substance, although the risk of causing alcohol misuse 
is low among women who already typically drinking small amounts each week
Non-Physical Risks
The questionnaires used in this study may be upsetting. If you find the 
questionnaires upsetting, you may speak with the research doctor or ask to be 
referred for additional emotional support. You may also skip any question that 
you do not wish to answer.
It is important that you tell the research doctor about all prescription and non-
prescription drugs, herbal preparations and nutritional supplements that you are 
taking or planning to take. 
During the research study, you will be notified of newly discovered side effects or 
significant findings, which may affect your health or willingness to participate.  
You may be asked to sign a new consent form that shows that you have been 
informed of new information relating to this research study.
D. WHAT WILL HAPPEN IF I
 AM REMOVED FROM THE STUDY OR DECIDE TO END MY 
PARTICIPATION IN THE RESEARCH?
You may be taken off the research study for any reason including:
It is considered to be in your best interest
The study treatment or procedures are found to be unsafe or ineffective
If you have any problems following study treatments and procedures
Your condition worsens
A decision is made to end the study
Or for other unforeseen reasons that make it necessary to stop your 
participation in the research study
You can also choose to stop participating in the research study at any time.  Tell 
the research doctor if you are thinking about stopping or decide to stop.  He or 
she will tell you how to stop.  Leaving the research study will not affect your 
medical care outside of the research study.  
6/23/2022 9:14 AM

Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 10 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
It is important to tell the research doctor if you are thinking about stopping so that 
you and your research doctor can discuss what follow-up care and testing could 
be most helpful for you.
It is important to note that although you may withdraw from study participation, 
the FDA requires that any information collected up to the point of your withdrawal 
not be removed from study records. Additionally, the research doctor may consult 
public records after you have withdrawn from the study.
If you agree to allow your blood and data to be kept for future research with 
identifying information that could link your sample to you, you may withdraw your 
permission at any time. We ask that you contact the study team and let them 
know you are withdrawing your permission for your identifiable blood and data to 
be used for future research.
E. WHAT ARE THE BENEFITS OF THIS RESEARCH STUDY?
Taking part in this research study may or may not benefit you.  We hope the 
information learned from this research study will provide more information about 
the effect of light alcohol intake on sex hormone levels in the presence of 
aromatase inhibitor therapy. 
F. WILL I
 BE PAID TO TAKE PART IN THIS RESEARCH STUDY?
The study sponsor will provide parking vouchers if plan to drive to the Clinical 
Research Center. In addition, you will be compensated for your time and effort at 
the end of each study visit, with a total of $130 for completing all 10 weeks of the 
study ($20 for Visit 1 (Baseline), $30 for Visit 2, $30 for Visit 3, and $50 for Visit 
4).
This research study will use a service called ClinCard® by the company 
Greenphire to manage all payments associated with your participation in study 
visits, your time and travel related to participation in the study. Additional 
information about the service will be provided to you in a separate document.   
G. WHAT ARE YOUR COSTS? 
Taking part in this research study will not lead to added costs to you or your 
insurance company. You will not be charged for the white wine, white grape 
juice, physical exams, and blood draws. 
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Research Consent Form
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BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 11 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
H. WHAT HAPPENS IF I
 AM INJURED BECAUSE I
 TOOK PART IN THIS RESEARCH STUDY?
If you think you have been injured as a result of taking part in this research 
study, tell the person in charge of this research study as soon as 
possible.  The research doctor’s name and phone number are listed in this 
consent form.
The treating hospital will offer you the care needed to treat injuries directly 
resulting from taking part in this research.  These treatments may be billed 
to you or your insurance company.  You will be responsible for 
deductibles, co-payments, and co-insurance.  There are no plans to pay 
you or give you other compensation for the injury. 
You do not give up any of your legal rights by signing this form. 
 
We will need to collect certain personal information about you for 
insurance or payment reporting purposes, such as your name, date of 
birth, gender, social security number, or Medicare identification number 
and information related to this research study. We may be required to 
report this information to the Centers for Medicare & Medicaid Services. 
We will not use this information for any other purpose.
If you go to the Emergency Room or to another hospital or doctor it 
is important that you tell them that you are in this research.  If 
possible, you should give them a copy of this consent form.
This trial does not involve treatment for a medical condition. You or your 
insurance company will be responsible for the cost of medical treatment. 
I. W
HOM DO I
 CONTACT IF I
 HAVE QUESTIONS ABOUT THE RESEARCH STUDY?
If you have questions about the study, please contact the research doctor or 
study staff as listed below:
Kenneth Mukamal, MD MPH:  
(617) 754-1409
Elizabeth Mostofsky, ScD:  
(617) 432-4023
For questions about your rights as a research participant, please contact a 
representative of the Office for Human Research Studies at Dana-Farber Cancer 
Institute (617) 632-3029. This can include questions about your participation in 
the study, concerns about the study, a research related injury, or if you feel/felt 
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OHRS Version: 1.31.2020
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DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
under pressure to enroll in this research study or to continue to participate in this 
research study. 
J. RETURN OF RESEARCH RESULTS
Tests done on samples in this research study are only for research and have no 
clear meaning for your health care.  For this reason, your study doctor will not 
share the results with you.
K.CLINICALTRIALS.
GOV 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, 
as required by U.S. Law.  This web site will not include information that can 
identify you.  At most, the web site will include a summary of the results.  You 
can search this web site at any time.
L.FUTURE USE OF DATA AND SPECIMENS
Your personal information and/or biospecimens collected during this study may 
be stored and used for future research.  Any personal identifiers will not be 
removed before they are shared so that the information or samples can be linked 
back to you by authorized personnel.
You will not be asked to provide additional informed consent for the use of your 
identifiable information or samples in future research.
M.CONFIDENTIALITY
We will take measures to protect the privacy and security of all your personal 
information, but we cannot guarantee the complete confidentiality of study data.  
Medical information created by this research study will not become part of your 
hospital medical record and will not be forwarded to your primary doctor. Trial 
information will be stored in your study file and it may also become part of a 
research database.  
The study team may publish the results of this research study and when we do, 
we may be asked to make the data we collect available to other researchers. We 
will not include information that identifies you in any publications or to the 
researchers who request the data to do additional research.
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Dana-Farber/ Harvard Cancer Center
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OHRS Version: 1.31.2020
Page 13 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
Your anonymized specimens may also be placed into one or more publicly-
accessible scientific databases.  Through such databases, researchers from 
around the world will have access to anonymized samples or data for future 
research.
There is a risk that anonymized research data that is shared with outside 
collaborators may be re-identified.  When anonymized data and specimens are 
shared with outside collaborators agreements limit what the outside collaborators 
can do with the information to help prevent re-identification.  
N.  FINANCIAL DISCLOSURES
It is possible that certain researchers on this study may have earned money 
from, or own some publicly-traded stock in, the company that makes or is 
developing the study intervention.  The amount of money that a researcher may 
earn and still take part in research is limited by the Harvard Medical School 
Faculty of Medicine Policy on Conflicts of Interest and Commitment. If you have 
further questions, please speak with a member of the study team or contact the 
Dana-Farber Cancer Institute Office of Research Integrity at 617-432-4557 or 
researchintegrity@dfci.harvard.edu.
O.CERTIFICATE OF CONFIDENTIALITY (C
OC)
To help protect your privacy, we have been issued a Confidentiality Certificate 
from the National Institutes of Health (NIH).  With this Certificate, the researchers 
on this study cannot be forced (for example, by court subpoena) to disclose 
information that may identify you in federal, state, or local civil, criminal, 
administrative, legislative or other proceedings.  
Disclosure will be necessary upon request of a United States federal or state 
government agency sponsoring the project that will be used for audit or program 
evaluation purposes or to meet the requirements of the federal Food and Drug 
Administration (FDA).
You should understand that a Certificate of Confidentiality does not prevent you 
or a member of your family or even the research doctor from voluntarily releasing 
information about yourself or your involvement in this research.  If an insurer, 
medical care provider, or employer learns about your participation and obtains 
your consent to receive research information, then we cannot use the Certificate 
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OHRS Version: 1.31.2020
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DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
of Confidentiality to withhold this information. This means that you and your 
family must actively protect your own privacy.
The Certificate of Confidentiality cannot be used to prevent disclosure to state or 
local authorities when there is a duty to report concerns of abuse, neglect, self-
harm, or a danger to others.  
To help protect your privacy, Beth Israel Deaconess Medical Center has obtained 
a Confidentiality Certificate from the Department of Health and Human Services 
(DHHS).  With this Certificate, Beth Israel Deaconess Medical Center cannot be 
forced (for example, by court subpoena) to disclose information that may identify 
you in federal, state, or local civil, criminal, administrative, legislative or other 
proceedings.
Disclosure will be necessary upon request of a United States federal or state 
government agency sponsoring the project that will be used for audit or program 
evaluation purposes or to meet the requirements of the federal Food and Drug 
Administration (FDA).
You should understand that a Certificate of Confidentiality does not prevent you 
or a member of your family or even the research doctor from voluntarily releasing 
information about yourself or your involvement in this research.  If an insurer, 
medical care provider, or employer learns about your participation and obtains 
your consent to receive research information, then Beth Israel Deaconess 
Medical Center cannot use the Certificate of Confidentiality to withhold this 
information. This means that you and your family must actively protect your own 
privacy.
The Certificate of Confidentiality cannot be used to prevent disclosure to state or 
local authorities when there is a duty to report concerns of abuse, neglect, self-
harm, or a danger to others.  
P.PRIVACY OF PROTECTED HEALTH INFORMATION (HIPAA
 AUTHORIZATION)
The Health Insurance Portability and Accountability Act (HIPAA) is a federal law 
that requires Dana-Farber/Harvard Cancer Center (DF/HCC) and its affiliated 
research doctors, health care providers, and physician network to protect the 
privacy of information that identifies you and relates to your past, present, and 
future physical and mental health conditions (“protected health information”).  If 
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Research Consent Form
Dana-Farber/ Harvard Cancer Center
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OHRS Version: 1.31.2020
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DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
you enroll in this research study, your “protected health information” will be used 
and shared with others as explained below.
1. What protected health information about me will be used or shared with 
others during this research?
Existing medical records, including mental health records.
New health information created from study-related tests, procedures, 
visits, and/or questionnaires
2. Why will protected information about me be used or shared with others?
The main reasons include the following:
To conduct and oversee the research described earlier in this form;
To ensure the research meets legal, institutional, and accreditation 
requirements; 
To conduct public health activities (including reporting of adverse events 
or situations where you or others may be at risk of harm); and
To provide the study sponsor with information arising from an adverse 
event or other event that relates to the safety or toxicity of the drug(s) 
used in the study and for the purpose of this or other research relating the 
study drug(s) and their use in cancer; 
To better understand the diseases being studied and to improve the 
design of future studies; and,
Other reasons may include for treatment, payment, or health care 
operations.  For example, some medical information produced by this 
research study may become part of your hospital medical record because 
the information may be necessary for your medical care. (You will also be 
given a notice for use and sharing of protected health information.)
3. Who will use or share protected health information about me?
DF/HCC and its affiliated research doctors and entities participating in the 
research will use and share your protected health information.  In addition, 
other DF/HCC offices that deal with research oversight, billing or quality 
assurance will be able to use and share your protected health information.
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Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 16 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
4. With whom outside of DF/HCC may my protected health information be 
shared?
While all reasonable efforts will be made to protect the confidentiality of your 
protected health information, it may also be shared with the following entities:
Outside individuals or entities that have a need to access this information 
to perform functions relating to the conduct of this research such as 
analysis by outside laboratories on behalf of DF/HCC and its affiliates (for 
example, data storage companies, insurers, or legal advisors).
The sponsor(s) of the study, its subcontractors, representatives, business 
partners, and its agent(s): National Institute on Alcohol Abuse and 
Alcoholism (NIAAA
Other research doctors and medical centers participating in this research, 
if applicable
Federal and state agencies (for example, the Department of Health and 
Human Services, the Food and Drug Administration, the National 
Institutes of Health, and/or the Office for Human Research Protections), or 
other domestic or foreign government bodies if required by law and/or 
necessary for oversight purposes. A qualified representative of the FDA 
and the National Cancer Institute may review your medical records.
Hospital accrediting agencies
A data safety monitoring board organized to oversee this research, if 
applicable
Some who may receive your protected health information may not have to 
satisfy the privacy rules and requirements.  They, in fact, may share your 
information with others without your permission. 
5. For how long will protected health information about me be used or 
shared with others?
There is no scheduled date at which your protected health information that 
is being used or shared for this research will be destroyed because 
research is an ongoing process.  
6. Statement of privacy rights:
You have the right to withdraw your permission for the research doctors 
and participating DF/HCC entities to use or share your protected health 
information.  We will not be able to withdraw all the information that 
already has been used or shared with others to carry out related activities 
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Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 17 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
such as oversight, or that is needed to ensure the quality of the study. To 
withdraw your permission, you must do so in writing by contacting the 
researcher listed above in the section: “Whom do I contact if I have 
questions about the research study?”
You have the right to request access to your protected health information 
that is used or shared during this research and that is related to your 
treatment or payment for your treatment, but you may access this 
information only after the study is completed.  To request this information, 
please contact the researcher listed above in the section: “Whom do I 
contact if I have questions about the research study?”
Q.DOCUMENTATION OF CONSENT
My signature below indicates:
I have had enough time to read the consent and think about 
participating in this study;
I have had all of my questions answered to my satisfaction;
I am willing to participate in this study;
I have been told that my participation is voluntary and I can withdraw at 
any time
Signature of Participant 
Date
or Legally Authorized Representative  
Relationship of Legally Authorized Representative to Participant  
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Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates 
OHRS Version: 1.31.2020
Page 18 of 19
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
To be completed by person obtaining consent:
Adult Participant
The consent discussion was initiated on  
 (date).
Signature of individual obtaining consent: 
Printed name of above: 
Date: 
A copy of this signed consent form will be given to the participant or legally authorized 
representative.
1) The participant is an adult and provided consent to participate.
1a)  Participant (or legally authorized representative) is a non-English speaker and
signed the translated Short Form in lieu of English consent document:
  As someone who understands both English and the language used by the participant, I     
interpreted and/or witnessed, in the participant’s language, the researcher’s presentation of 
the English consent form.  The participant was given the opportunity to ask questions. 
Signature of Interpreter/Witness: 
Printed Name of Interpreter/Witness: 
Date: 
1b)  Participant is physically unable to sign the consent form because: 
 The participant is illiterate.
 The participant has a physical disability.
 Other (please describe): _________________________________________
The consent form was presented to the participant who was given the opportunity 
to ask questions and who communicated agreement to participate in the research. 
Signature of Witness: 
Printed Name of Witness: 
Date: 
2) The participant is an adult who lacks capacity to provide consent and his/her legally
authorized representative:
2a) gave permission for the adult participant to participate 
2b) did not give permission for the adult participant to participate 
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Informed Consent Documentation 
To be signed by the person obtaining informed consent.
Date of Informed Consent:  
 Initial Consent
Re-consent
Participant Identifier:     
Protocol #:  
Was a witness present?  
 Yes* 
No 
*Witness Name:
The content of the informed consent document was fully explained.
The participant was given adequate time to review the consent form and
received an explanation of the content of the informed consent document.
The participant had an opportunity to ask questions and all of the participant’s
questions regarding the study were answered to their satisfaction.
The participant completed all sections of the informed consent document, and
signed and dated the informed consent document.
The participant received a signed and dated copy of the informed consent
document.
Additional comments:
By signing below, I attest that the informed consent process was conducted as indicated 
above..
Signature:
Date:
Printed Name:
DFCI Protocol Number: 21-698 
Approved Date (DFCI IRB Approval): 04/18/2022 
Date Posted for Use: 06/23/2022 
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