Clinical trial NCT04770493
Conditions: Alcohol Use Disorder
Keywords: Alcohol Teenager Medication Clinical Trial
Sponsor: Brown University
Start date: 2022-01-24; Completion date: 2024-10-24
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will help determine the tolerability and efficacy of the mood-stabilizing anticonvulsant lamotrigine in youth with alcohol use disorder. It will also help establish whether and how lamotrigine improves outcomes related to alcohol use. The results of this proof-of-concept study will inform whether a future larger clinical trial is warranted.

Detailed description:
Adolescent alcohol use is a leading public health concern worldwide. Clinical trials have tested a variety of psychosocial interventions with youth that yield only modest short-term benefits. One potential way to improve treatments is to augment psychosocial interventions with pharmacotherapy. The National Institutes of Health has mounted a concerted effort to identify medications that reduce drinking for nearly three decades. Although this effort improved treatment for adults, no medication is indicated for adolescent use and randomized controlled trials with teenagers are almost nonexistent. This gap raises key questions about whether and how medications could benefit youth. Optimizing treatment options for youth requires closing this important gap. Lamotrigine is safe with adolescents and does not adversely interact with alcohol. Lamotrigine targets brain mechanisms implicated in alcohol use disorder, and it has shown to help treat adults with alcohol problems. Yet, despite its widespread use with children and adolescents, no published double-blind, placebo-controlled studies have examined the effects of lamotrigine on drinking-related behavior in youth. The purpose of this study is to determine how well teenagers accept lamotrigine plus alcohol education to reduce adolescent alcohol use. This study will also tell us whether teenagers' alcohol use, craving, and enjoyment of drinking are reduced by lamotrigine.

Arms: arm 1: Lamotrigine (25 mg/day to 200 mg/day in two divided doses) for 9 weeks arm 2: Identical matching placebo capsules
Interventions: intervention 1: Lamotrigine intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will be randomized to lamotrigine (25 mg/day to 200 mg/day in two divided doses) for 9 weeks. A comparator group will receive placebo (sugar pills). intervention 2: Matching placebo (sugar pill)

Protocol documents:
Prot_SAP_000.pdf: 
                                              
Enhancing the Effects of Alcohol Treatment with Lamotrigine 
 
Principal Investigator: 
Robert Miranda Jr., PhD, ABPP 
ClinicalTrials.gov ID: 
NCT04770493 
Date:  
 
 
February 02, 2021 
 
 
  
 
 
 
 


Rationale 
Alcohol use disorder (AUD) affects nearly one-third of adults in the United States during 
their lifetime. Excessive alcohol use causes myriad acute and long-term medical, 
psychological, and social problems. It carries an economic burden of $249 billion 
annually. Although advances in pharmacotherapy have improved treatment options for 
adults with AUD, treatment options for youth are limited.  
Adolescent and young adult alcohol use is a leading public health concern. The harmful 
effects of underage drinking are irrefutable and include premature death and possibly 
irreversible damage to the developing brain. In addition, adolescence is a critical period 
in the pathogenesis of AUD; an estimated 3 to 15% of youth develop AUD before age 
18. Clinical trials have tested psychosocial interventions with youth, including family 
treatments, cognitive behavior therapy (CBT), and motivational enhancement therapy 
(MET), that yield only modest short-term benefits. Our group has contributed 
substantially to this work.  
One potential way to improve treatments is to augment psychosocial interventions with 
pharmacotherapy. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has 
mounted a concerted effort to identify medications that reduce drinking for nearly three 
decades. Although this effort improved treatment for adults, no medication is indicated 
for adolescent use, and randomized controlled trials with teenagers are almost 
nonexistent. This gap raises key questions about if and how medications could benefit 
youth. The urgency of this issue is underscored by the fact that optimizing treatment 
options for youth requires closing this critical gap. 
Anticonvulsants are increasingly found to be efficacious for treating AUD. Many have 
intolerable side effects, however, that greatly limit their utility. Lamotrigine is a new 
generation mood-stabilizing anticonvulsant approved by the FDA to treat epilepsy in 
patients two and older and bipolar disorder in adults with fewer side effects than older 
anticonvulsants. We propose to study lamotrigine for three primary reasons.  
• First, lamotrigine is safe and well tolerated by youth. 
• Second, lamotrigine targets brain mechanisms implicated in the pathogenesis of 
AUD, namely the glutamatergic system, which mediates the acute and chronic 
effects of alcohol. 
• Third, mounting human research that shows lamotrigine reduces alcohol and 
other substance use as well as craving. 
On the whole, modulation of the glutamatergic system is a key pharmacological target 
for AUD treatment. Anticonvulsants reduce alcohol and other drug use in adults and 
adolescents but are not well tolerated. There is strong preclinical and emerging clinical 


evidence that lamotrigine also reduces alcohol and other drug use, and human studies 
show it is well tolerated. 
Objectives 
The primary objectives of this study are twofold. The first primary objective is to evaluate 
the feasibility, acceptability, and tolerability of lamotrigine (25 mg/day to 200 mg/day in 
two divided doses) as compared to placebo for 9 weeks plus a psychosocial platform 
comprised of motivational enhancement therapy and cognitive behavioral therapy (MET-
CBT; “Path 180”) among adolescents and young adults (ages 16 to 24 years) with AUD 
as confirmed by the Diagnostic and Statistical Manual of Mental Disorders – Fifth 
Edition (DSM-5™). 
The second primary objective is to leverage a human laboratory paradigm to evaluate 
the effects of lamotrigine on an intermediate phenotype associated with alcohol use and 
outcomes in clinical trials. Specifically, we hypothesize that lamotrigine, as compared to 
placebo, will decrease alcohol cue-elicited craving in the human laboratory during in 
vivo alcohol cue reactivity. 
Methodology 
This proof-of-concept study is a double-blind, randomized, placebo-controlled, parallel 
group, single-site clinical trial. After obtaining consent/parent permission/assent, 
potential subjects and, if younger than 18 years, their parent(s) will complete a medical 
history and psychiatric diagnosis interview (about the adolescent) to screen for eligibility. 
Youth will also complete a physical examination, vital signs, drinking history and an 
alcohol breathalyzer test. 
Forty-four eligible subjects will be randomized in an approximate 1:1 ratio to either 
lamotrigine or placebo for 9 weeks. 
Dose titration, maintenance and taper will occur as scheduled below. Lamotrigine will be 
self-administered by subjects once daily after eating and with a full glass of water 
beginning on Study Week 1, Day 1 and continuing through Study Week 11, Day 7. The 
first dose will be taken in the study clinic whenever possible. Subjects will be provided 
with water and a snack to take with first dose. Dose will be titrated, as tolerated, to a 
target dose of 200 mg in two divided doses per day of lamotrigine. Following the target 
dose period, participants will complete a 2-week medication taper period (see dosing 
schedule below).Capsules should be swallowed whole and should not be cut, crushed, 
or chewed. Capsules should be taken with food and water. 
 
 


 
Schedule of Administration of Investigational Product 
Study Period 
Time Period 
Daily Dose 
Dosing Schedule 
Titration 
Weeks 1-2 
25 mg  
Once daily 
 
Weeks 3-4 
50 mg 
Two divided doses 
 
Week 5 
100 mg 
Two divided doses 
 
Week 6 
150 mg 
Two divided doses 
Maintenance   
Week 7-9 
200 mg  
Two divided doses 
Taper 
Week 10 
100 mg 
Two divided doses 
 
Week 11 
50 mg 
Two divided doses 
 
At the randomization/baseline visit and after 7 weeks of investigational product 
administration (i.e., Study Week 8), subjects will undergo a human laboratory paradigm 
(i.e., alcohol cue reactivity assessment). 
Main Inclusion/Exclusion Criteria: Subjects will be male and female adolescents, ages 
16 to 24 years old, who meet DSM-5 criteria for AUD. They must be seeking to reduce 
their alcohol use.  
Investigational Product, Dosage and Mode of Administration: Lamotrigine (titrated for 6 
weeks; target dose [200 mg/day/BID] for 3 weeks) will be over encapsulated and 
supplied by a contracted pharmacy, along with identical matching placebo capsules.  
Reference Therapy, Dosage and Mode of Administration: Identically over encapsulated 
placebo tablets will be dispensed according to the same schedule as the lamotrigine 
capsules. 
 
Statistical Analysis Plan 
Primary Objectives 
• 
Feasibility of retention will be determined by the percentage of enrolled subjects 
who complete the protocol (target ≥ 70%) and treatment-specific retention rates. 
• 
Acceptability will be determined based on overall study withdrawal rates (≤ 20% 
considered acceptable), as well as treatment-specific withdrawal rates. Treatment 
satisfaction will be considered acceptable if ≥ 80% of responses on the CSQ-8 are rated 


either “satisfactory” or “highly satisfactory.” We will also examine reasons for termination 
qualitatively. 
Secondary Objectives 
• 
 We hypothesize that lamotrigine, as compared to placebo, will decrease alcohol 
craving during an alcohol cue-exposure paradigm in the human laboratory. 

ICF_001.pdf: 
BROWN UNIVERSITY 
We invite you to be part of a research study directed by Dr. Robert Miranda and his associates at 
Brown University. You were selected as a possible participant in this study because you said you’re 
interested in reducing your alcohol use. 
The researchers will explain this study to you. Research studies are voluntary and include only 
people who choose to take part. Please take your time about deciding whether to participate in this
study. Before deciding: 

You can discuss this study with your parents.

You can also discuss it with your health care doctor.

If you have any questions, you can ask the researchers for more information.
KEY INFORMATION 
•
PURPOSE: This study is about whether the study medicine plus alcohol education helps teenagers
reduce their alcohol use. In this document, you will see the terms medication, treatment, and treatment
period. These are terms used in research studies; they do not mean that you will be receiving medical
treatment for any condition.
•
PROCEDURES: You will take a study medication for 9 weeks; answer personal questions, such as
questions about drug and alcohol use, both in person and in your daily life using a smartphone;
complete medical tests, including an alcohol breathalyzer, physical exam, heart rate, blood pressure, a
urine drug test and, if female, a pregnancy test; provide a blood sample; go through a task where you
look at water and an alcoholic drink and answer questions; and take part in 7 computerized alcohol
education sessions.
•
TIME INVOLVED: After screening and during the 9-week study, you will attend weekly 30-minute
visits; seven 30-minute computerized alcohol education sessions; two 2-hour and one 1-hour assessment
sessions; three 10-minute phone calls over two weeks when you first start taking the study medicine; two
10-minute phone interviews while you stop taking the study medicine over a 2-week period; one
10-minute phone interview 2-weeks after you finish taking the study medicine; and one
30-minute phone interview 3-months after you finish taking the study medicine.
•
COMPENSATION: If you complete the study, you will receive up to  $527 for your time.
•
RISKS: Possible risks include discomfort or bruising with drawing blood; loss of privacy; undue
influence; discomfort answering personal questions; and side effects of the medication, such as
dizziness, tremor, headache, rash, blurred or double vision, fever, lack of coordination, abdominal pain,
sleepiness, back pain, nausea, vomiting, diarrhea, tiredness, insomnia, dry mouth, confusion,
paresthesia (burning sensations) and amblyopia (lazy eye).
•
BENEFITS: The computerized alcohol education sessions may help you cutback or quit alcohol.
•
ALTERNATIVES TO PARTICIPATION: We do not offer other options. There are local treatment
programs, however, and you will get a list of those services.
•
REMOTE OPTION: If in-person visits are not possible, we may offer you the option to have some
of your visits completed remotely, via telephone or Zoom video conference. Parts of the in-person visits
that cannot be done over the telephone or Zoom video conference may be excluded or rescheduled. You
may be asked to sign in or download an app to use Brown University’s Zoom platform for
teleconferencing, depending on your device, and you will need WIFI connection.
CONSENT FOR RESEARCH PARTICIPATION 
Effects of Lamotrigine on Adolescent Alcohol Use 
Version 5.0 20DEC2021
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
1


To see if the study is a good fit, what is one thing that you will need to complete? 
WHY IS THIS STUDY BEING DONE? 
This study will test if a medicine called lamotrigine helps young people reduce their alcohol use. 
Lamotrigine is a mood- stabilizing anticonvulsant or antiepileptic medication approved by the U.S. Food 
and Drug Administration (FDA) to treat epilepsy in patients two and older. We hope it will help youth 
reduce their drinking. But we don’t know this for sure. There is no medicine to help teenagers reduce 
their alcohol use. This drug appears to reduce alcohol use in adults with co-occurring mood and alcohol 
problems. This study is the first to test its effects on alcohol use among teenagers who want to reduce 
their drinking. 
WHAT WILL HAPPEN IF YOU TAKE PART IN THIS STUDY? 
Before you begin the study: 
Before you begin this study, we need to find out if this study is right for you. This screening takes
about 2.5 hours. You will take an alcohol breath test and if your alcohol level is above 0.00% at any 
study visit you will need to return another day. 
We will ask you questions about your health and alcohol and drug use. You will give urine and blood 
samples and have a physical exam by a study doctor. We will test urine for illegal drugs and, if female, 
pregnancy. If your urine is positive for any illegal drug except marijuana, you won’t be able to be in the 
study. 
Females cannot be in this study if they are pregnant or breastfeeding. It is not known if the study 
medication may harm an unborn baby. The study medication can reduce the effectiveness of oral 
contraceptives (birth control pills) or other female hormonal medicines. Sexually active females cannot 
be in this study if they do not agree to use a barrier method of birth control (condom). 
During the study:
•
If you are a good fit for this study, you will come to our office for a pre-medication session. You will take
an alcohol breath test, urine drug test and, if female, a pregnancy test. You will answer more questions
about yourself. We will record your heart rate, blood pressure, and urge to drink alcohol while you relax
and while you look at water and an alcoholic drink. This is called a cue reactivity assessment. It may take
time for your urge to go down. If your urge remains high, you will meet with a study clinician to help
manage your craving. This session will take about 2.5 hours.
•
You will attend 9 weekly checkup visits at our office, each lasting about 30 minutes. During these visits,
you will complete an alcohol breath test and provide a urine sample to test for drug use and, if female,
pregnancy. We will record your blood pressure and heart rate. We will also ask you about side effects,
your mood, any new medications or therapy, and recent alcohol and drug use. Once you start the study
medicine, you will return any unused capsules and get more.
•
You will complete three telephone interviews. These are brief interviews that last about 10 minutes; two
happen in Week 1, and one happens in Week 2. We'll ask about any side effects, other medication use or
counseling, alcohol withdrawal symptoms, and the number of medication capsules you’ve taken. We’ll
also remind you about dose increases and your next scheduled visit.
•
You will also receive in 7 computerized alcohol education sessions (Weeks 1, 2, 3, 4, 5, 7, and 9) about your
alcohol use, including your thoughts about cutting back, how your drinking compares to others, and how
alcohol is harmful. We’ll help you track your drinking and set goals to cut down. Everyone will get the
alcohol education program regardless of how much they drink. Each session lasts about 30 minutes. If
possible, sessions will happen on the same days as your weekly checkups.
2 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022


Please explain two or three things that will happen if you decide to participate in this study. 

For nine weeks, you will take medication capsules that contain lamotrigine or placebo. If you take
lamotrigine, the dose will start at 25 mg per day for Weeks 1 and 2, then increase to 50 mg per day for
Weeks 3 and 4, 100 mg/day for Week 5, 150mg Week 6 and Weeks 7-9 will be at the highest dosage of
200mg/day. You’ll take the same type of capsule (lamotrigine or placebo) during the 9-week study.
About one-half of youth will get the study medicine; the other half will take placebo pills that look
like medicine but are not real. Placebo pills should have no physical effect on you. We will use a
method of chance to decide the group you’re in (e.g., medication assignment). This method is like
flipping a coin. You will not know which group you are in. Neither will the researchers. A
prescription for the study medicine or placebo will include your name, address, and date of birth.
■
You will use a study smartphone or download an app to answer questions as you go about your daily
life for nine weeks. For the first 6 weeks you will answer questions when you wake up and when you
take your study medication. The last three weeks you will answer questions when you wake up, drink
alcohol, take medication, and when it beeps (about 4 times per day).You’ll record where you are, what
you’re doing, how you’re feeling, urges to drink, and how many alcoholic drinks you drank (if any).
We’ll check in to see how you’re doing and answer any questions. We recommend that you respond to
the app at a time and place that allows for privacy. You can skip or delay responding when necessary.
This app does not require WIFI or internet connection to work.

During the Week 8 checkup visit, you will do a second cue reactivity assessment just like the first.
We’ll measure your urge to drink alcohol while you relax and while you look at water and an
alcoholic drink. You will also provide a blood sample to test the levels of study medicine in your
blood. This entire visit, combined with the alcohol education session, will take about 2.5 hours.

At the end of the 9-week study, you will complete a final in-clinic visit that takes about 60 minutes
and reduce and stop your medication dose over two-weeks. You will complete two phone interviews
while you stop the medicine over two-weeks (1 each week). You will also complete a brief phone
interview 2 weeks after you completely stop the study medicine.
After you finish alcohol education and the study medicine: 
You will complete a brief follow-up interview over the phone, 3-months after you finish the study 
medicine, about your recent alcohol and drug use. This interview will take about 30 minutes. 
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
3


SCHEDULE OF ASSESSMENTS 
Phone 
Pre-Medication 
Weekly Checkup Visits 
Final In- 
Clinic 
Visit 
Checkups 
(Weeks 
10, 11,& 13) 
3- month
Follow-up 
Interview 
*You will complete two phone interviews while you stop the medicine over two-weeks (1 each week). You will also complete a brief
phone interview 2 weeks after you completely stop the study medicine.
HOW LONG WOULD YOU BE IN THIS STUDY? 
The study takes about 9 weeks plus two brief phone interviews while you are stopping the study medicine 
over a 2-week period and two more brief phone interviews that occur 2-weeks and 3-months after you 
finish taking the study medicine. 
WILL YOU BE PAID FOR YOUR PARTICIPATION? 
If you complete the study, you will get up to $527.00. You will be paid in gift cards for the screening 
session. If you are eligible and enroll in the study you will be paid in gift cards and/or ClinCard (see 
below), based on your choice. We will pay you for all parts of the study you complete, even if you 
decide to stop the study early for any reason. The payment schedule will be as follows: 
$20 
$20 
$20 
$180 $20 for each checkup completed 
$147 $1 per day for first 6 weeks 
$5 per day for last 3 weeks 
$20 
$40 For returning remaining capsules and the 
smartphone (if applicable) 
$40 $20 for each interview completed 
$20 
Screening session 
Blood tests & physical exam 
Baseline session 
9 weekly checkup visits 
9-week smartphone period
Final in-clinic visit 
Bonus 
2 phone interviews while stopping study medicine 
2-week phone interview
3 month phone interview
$20 
Total 
$527 
Screening 
Session 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Alcohol 
breathalyzer 
• 
• 
•
• 
•
• 
•
• 
•
• 
• 
• 
Blood pressure & 
heart rate 
• 
• 
•
• 
•
• 
•
• 
•
• 
• 
Blood draw 
• 
• 
Phone interview 
(10 min.) 
• 
• 
• 
Cue reactivity 
assessment 
• 
• 
Interviews & 
questionnaires 
• 
• 
•
• 
•
• 
•
• 
•
• 
• 
• 
Physical Exam 
• 
Smartphone 
assessments 
•
• 
•
• 
• 
• 
•
• 
•
Urine drug test 
• 
• 
•
• 
•
• 
•
• 
•
• 
•
• 
Urine pregnancy 
test 
• 
• 
•
• 
•
• 
•
• 
•
• 
•
• 
Phone interviews 
(10 min.)* 
• 
Phone interview 
 (30 min.) 
• 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
4


If you choose, payment for participating in this study may be made using ClinCard, a pre-paid Mastercard 
that works like a debit card. 
We will give you the card. You will be given one card for the entire time of your participation and this card 
may be used to pay you in any future Brown University studies that use ClinCard. You will also get 
information about how to use this card and whom to call if you have any questions. Be sure to read this 
information, including the cardholder agreement from Greenphire. 
Money will be added to your card based on the study’s payment schedule. You may use this card online or at 
any store that accepts Mastercard. Please read the FAQ information sheet from your study coordinator for 
details about the ways you can use the card, some of which may involve fees that will reduce the amount of 
money on the card. 
If you earn $600 or more from Brown University in a single calendar year (either in a one study or across 
multiple studies), Brown will ask for your social security number to correctly identify you in the payment 
system and send you an IRS 1099 Form. You may also be asked to complete a Form W9. This may affect your 
taxes. Only payments for being in research studies will be used to decide if you should receive the IRS form. 
Money for study-related parking, food, and other expenses are not included in this IRS disclosure. 
This card is administered by an outside company called Greenphire. Greenphire will be given your name, 
address, and date of birth. They will use this information only as part of the payment system, and it will not be 
given or sold to any other company. Greenphire will not receive any information about your health status or 
the study in which you are participating. 
If your card is lost or stolen, please call the study coordinator for a free replacement card. If you request a 
replacement card from Greenphire directly, you may be charged a fee. 
Please note that you do not need to use ClinCard to be in this study. You can chose to receive study payments 
in gift cards instead. 
WHAT KINDS OF RISKS OR DISCOMFORTS COULD YOU EXPECT? 

Potential study medicine risks: Many studies have researched the effects of lamotrigine in children
(ages 2 years and older), teenagers, and adults. Studies show it is safe with teenagers and it does not
harmfully interact with alcohol in adults; interactions with alcohol are unknown in adolescents.
Adult heavy drinkers, non-heavy drinkers, and non-drinkers tolerate this medicine equally well.
Rare but Serious 
Dermatological 
Reactions 
Serious skin rashes, such as Stevens-Johnson and toxic epidermal necrolysis, 
have been caused by lamotrigine. They are more common in pediatric patients and
when lamotrigine is administered with valproic acid [Depakote]). Stevens-Johnson 
syndrome is a rare but serious condition that could require hospitalization if not 
recognized and treated. 
Most Common 
Side Effects 
■
Blurred or double vision
or other changes in vision
■
Diarrhea
■
Nausea
■
Vomiting
■
Indigestion
■
Skin rash
■
Clumsiness or unsteadiness
■
Poor coordination
■
Dizziness
■
Tiredness
■
Trouble sleeping
■
Headache
Less Common 
Side Effects 
■
Abdominal pain
■
Constipation
■
Sore throat or dry mouth
■
Loss of strength
■
Menstrual pain
■
Unusual weight loss
■
Anxiety
■
Confusion
■
Depression or irritability
■
Chest pain
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
5


■
Pain
■
Runny nose
■
Slurred speech
■
Trembling or shaking
■
Vertigo or a sensation of
feeling off balance
■
Confusion
■
Continuous, uncontrolled back- 
and-forth or rolling of the eyes
■
Seizures
■
Infection
FEMALES SHOULD NOT TAKE LAMOTRIGINE IF THEY ARE PREGNANT OR BECOME 
PREGNANT DURING THE STUDY. 
o
Lamotrigine can reduce the effectiveness of oral contraceptives (birth control pills) or other
female hormonal medicines. Before taking lamotrigine, tell your study physician if you are taking
oral contraceptives (birth control pills) or other female hormonal medicines. Do not start or stop
taking birth control pills or other female hormonal medicine until you have talked with your
study physician. Tell your study physician if you have any changes in your menstrual pattern,
such as breakthrough bleeding. Stopping these medicines while taking lamotrigine may cause side
effects (such as dizziness, lack of coordination, or double vision). Starting these medicines may
lessen how well lamotrigine works.
o
Sexually active females cannot be in this study if they do not agree to use a barrier method of
birth control (condom) every time they engage in sexual intercourse.
o
It is not known if lamotrigine may harm an unborn baby.
o
If you become pregnant during the study, notify your study physician immediately. In addition,
you can talk with your study physician about registering with the North American Antiepileptic
Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of
the registry is to collect information about the safety of antiepileptic drugs during pregnancy.
In addition, you should not take lamotrigine if: 
o
You have kidney or liver impairment
o
Previous history of a harmful drug reaction that affects the skin, white blood cells, and various
internal organs.
o
You are allergic to lamotrigine (active ingredient: lamotrigine; inactive ingredients: lactose;
Rare 
Side Effects 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
Blistering, peeling or 
loosening of skin 
Liver failure 
Dark-colored urine 
Fever 
Chills 
Flu-like symptoms 
General feeling of 
discomfort or illness 
Cough 
Memory loss 
Itching 
Muscle cramps 
Red or irritated eyes 
Small red or purple spots 
on skin 
Sores, ulcer, or white 
spots on lips or mouth 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
Swelling of face, mouth, hands, 
or feet 
Swollen lymph nodes 
Anemia 
Trouble breathing 
Unusual bleeding or bruising 
Unusual tiredness or weakness 
Yellow eyes or skin 
Loss of appetite 
Allergic reactions 
Blood dyscrasias (drop in blood 
counts) 
Suicidal thoughts or behaviors, 
Aseptic (non-infectious) 
meningitis 
■ 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
6


Please explain two or three risks of participating in this study. 
magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, FD&C 
Yellow No. 6 Lake (100-mg tablet only), ferric oxide, yellow (150-mg tablet only), and FD&C 
Blue No. 2 Lake (200-mg tablet only) 
Before taking lamotrigine notify us of all health conditions (or a family history of), especially:
Suicidal thoughts or actions 
Heart problems or defects 
Had a rash or allergic reaction 
to anti-seizure medication 
Irregular heartbeat 
High or low blood pressure 
Psychosis 
Kidney impairment 
Mania or bipolar illness 
Depression 
Mental health problems 
Liver impairment 
The study medicine may change how other medications work. So, it is very important to tell us about 
any new medications you use during the study so we can make sure it’s safe. This is especially true if 
you take medication that includes acetaminophen (Tylenol), valproate acid (Depakote), 
carbamazepine (Tegretol XR, Equetro, Epitol), phenytoin phenobarbital, primidone (Mysoline), and 
rifampin and protease inhibitors lopinavir/ritonavirand atazanavir/lopinavir (HIV antivirals). 
Be careful driving or using machinery until you know how the medication affects you. It may make 
you feel sleepy or dizzy, making it hard to drive or perform other activities safely. 

Placebo risks: Placebo pills will contain microcrystalline cellulose, a commonly used inactivefiller,
and 50 mg of riboflavin. Riboflavin is an easily absorbed water-soluble vitamin (B2). There are no
known toxic or adverse reactions to riboflavin in humans.

Blood draw risks: Problems drawing blood rarely occur. These include temporary discomfort from
the needle stick, local bleeding, a lump or bruising and, rarely, infection, lightheadedness and
fainting. Only a small amount of blood will be taken, about 2 teaspoonfuls.

Psychological risks: Some questions we ask may be upsetting or you may feel uncomfortable
answering them. If you do not wish to answer a question, you can skip it and go to the next.

Loss of confidentiality: As this study involves the use of your identifiable, personal information,
there is a chance that a loss of confidentiality or privacy will occur. We have procedures in place to
reduce the chances of this happening (see “How will information about you and your participation
be kept private?” section below).

Undue influence: Undue influence can happen when the payment you get is large. Such pressure is
unlikely in this study because payments are fair for the time and effort required and like other studies
in the area. There will be no other rewards or payments. Even if you stop, we will pay you for any
time you were in the study. If you decide not to participate in this study or decide to stop the study,
you will not lose access to needed health services available outside the study.
Unknown risks and discomforts: 
The study medicine may have side effects that no one knows about yet. The researchers will let you 
know if they learn of anything that might make you change your mind about participating in this 
study. 
WHO TO CONTACT IF YOU HAVE A STUDY-RELATED INJURY, ILLNESS, OR DISTRESS? 
If you have any questions, concerns or complaints about this study or to report a study-related injury, 
contact Robert Miranda, Jr., Ph.D. or a study physician at 1-800-759-6045. If you get sick or have any
problems from taking the study drug you must call your study doctor at this number right away. We will 
provide emergency care, if necessary, but Brown University and the researchers assume no responsibility 
to pay for such care or to provide financial compensation for emergency or non-emergency health services. 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
7


If you are unable to reach anyone at the number listed above and you require immediate (life threatening) 
medical attention, please go to your nearest emergency room. 
ARE THERE ANY BENEFITS IF YOU PARTICIPATE? 
You may or may not directly benefit from being in this research study. You will get the alcohol 
education program even if you decide to stop the study medication. You will also have the chance to 
contribute to research that may be helpful to you or to others in the future. 
WHAT OTHER CHOICES DO YOU HAVE IF YOU DON’T WANT TO PARTICIPATE? 
If you decide not to participate in this study, we do not offer any other study. There are treatment 
programs in Rhode Island, however, and we will give you a list of those services. 
HOW WILL INFORMATION ABOUT YOU AND YOUR PARTICIPATION BE KEPT PRIVATE? 
Use of personal information that can identify you: 
Any information we collect about you as part of this study that identifies you will remain private. Only a 
code number will be used to identify your private information; your name will not be matched with your 
private information. We will keep all information about you locked up and password protected. It will be 
disclosed only with your permission or as required by law. In accordance with federal FDA requirements, all 
study records must be retained for at least three [3] years after the completion of research. 
Clinical research relies on truthful data collected from you without the fear of disclosure of your sensitive 
information. Congress authorized the Secretary of Health and Human Services to issue Certificates of 
Confidentiality that allows research investigators to refuse to disclose identifiable information about you 
even under a subpoena. This study has been issued a Certificate of Confidentiality from the National Institute 
on Alcohol Abuse and Alcoholism (NIAAA). The researchers can use this Certificate to legally refuse to 
disclose information that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the 
Certificate to resist any demands for information that would identify you. 
The Certificate cannot be used, however, to resist a demand for information from personnel of the United 
States federal or state government agency sponsoring the project and that will be used for auditing or 
program evaluation of agency funded projects or for information that must be disclosed in order to meet the 
requirements of the federal FDA. 
You should understand that a Certificate of Confidentiality does not prevent you or a member of your family 
from voluntarily releasing information about yourself or your involvement in this research. If an insurer, 
medical care provider, or other person obtains your written consent to receive research information, then the 
researchers will not use the Certificate to withhold that information. 
As a participant in this study, you must also do your part in protecting your identity and your sensitive 
information linked to this study: The Certificate of Confidentiality remains protective if you do not disclose 
your participation to others. Once disclosure is in the public domain, it’s possible that the Certificate of 
Confidentiality can be challenged. 
If you give us your permission by signing this document, information, which does not identify you by name, 
may be used for scientific purposes, including teaching or publication. Because of the 
investigational nature of this study, the study sponsor, the Brown University Institutional Review Board, the 
FDA, the Department of Health and Human Services, the Offices of Inspector General and Civil 
Rights have the right to review study records. Your information will be kept confidential. Your name, 
address, and date of birth may be used to fill an individualized prescription for lamotrigine or placebo 
capsules. This information will be disclosed to a study pharmacy and blood laboratory, when applicable, 
which adheres to the Health Insurance Portability and Accountability Act (HIPAA) practices and stores this 
information in a private, password protected and encrypted format.
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
8


When are the researchers required to share some of your private information with authorities? 
Can you change your mind and stop your participation in this study? 
How information about you will be stored: 
We maintain all research data and records in a secure location at Brown University. Only authorized 
individuals will have access to it. 
When will we share some of your private information with others: 
Instances when information will not be kept confidential or private involve reports of child abuse, elder 
abuse, or threats to harm yourself or others. If you report suicidal or homicidal intent or ideation or child or 
elder abuse, the principal investigator, a clinical psychologist, or study physician will be notified 
immediately. A report will be filed with the appropriate authorities if abuse is reported. 
WHO CAN YOU CONTACT IF YOU HAVE QUESTIONS ABOUT THIS STUDY? 
The Research Team: 
You may contact Dr. Robert Miranda at 401-863-6658 or by email at Robert_Miranda_Jr@brown.edu 
with any questions or concerns about the research or your participation in this study. Additionally, you 
may contact research staff Brianna Parlette at 401-863-6687 or by email at Brianna_Parlette@brown.edu. 
Brown University Human Research Protection Program (HRPP): 
People and agencies that will have access to your information: 
The National Institutes of Health, the Brown University Institutional Review Board, the FDA, the 
Department of Health and Human Services, the Offices of Inspector General and Civil Rights have the 
right to review study records. 
Members of our research team are part of the Lifespan health system and Rhode Island Hospital and will
have access to the study records. An individual prescription for the study medicine or placebo will include 
your name, 
address, and date of birth. In addition, for your blood samples to be processed, the laboratory order will 
include your name, sex at birth and date of birth. We will share this information with the study pharmacy 
and blood laboratory, which adheres to HIPAA practices and stores this information in a private, 
password-protected, and encrypted format. 
Information collected during this study will be stored in a central repository at the National Institutes 
of Health (NIH). None of the information shared with the NIH can be used to identify you; it will be 
anonymous. Any information that could identify you will be removed. The purpose of storing data at 
the NIH is to make information available for use in research for this study and health-related research 
in the future, after the current study is completed. Sending information to the repository may give 
scientists valuable research material that can help them to develop new diagnostic tests, new 
treatments, and new ways to prevent diseases. 
ARE THERE ANY COSTS FOR TAKING PART IN THIS STUDY? 
There will be no cost to you for being in this study. 
WHAT IF YOU WANT TO STOP PARTICIPATING IN THIS STUDY? 
You do not have to be in this study if you do not want to be. Even if you decide to be in this study, you can 
change your mind and stop at any time. Refusing to participate in or stop the study will not affect your 
current or future relationship with Brown University, Dr. Robert Miranda, or other researchers. If you want 
to stop, it is important to tell us so that we can get any remaining medication and, if necessary, the 
smartphone device from you. 
CONSENT FORM (20DEC2021)
Brown University IRB Amendment Approval: 12/22/2021
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
9


Please check whether you agree to be re-contacted for future studies and initial. 
Yes 
 No 
 (Initial) 
If you have questions about your rights while taking part in this study, or you have concerns or 
suggestions about the study and you want to talk to someone other than the researchers, you may 
contact Brown’s HRPP at 401-863-3050 or email them at IRB@Brown.edu. 
WHERE CAN YOU FIND PUBLIC INFORMATION ABOUT THIS STUDY? 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by US 
Law. This Web site will not include information that can identify you. At most, the website will include 
a summary of the results. You can search this website at any time. 
AGREEMENT TO BE IN THE STUDY 
This consent form contains important information to help you decide if you want to be in this study. If you 
have any questions that are not answered in this consent form, ask one of the study staff. 
Please answer YES or NO to the following questions: 
A.
Is this document in a language you understand?
B.
Do you understand the information in this consent form?
C.
Have you been given enough time to ask questions and talk about the study?
D.
Have all your questions been answered to your satisfaction?
E.
Do you think you received enough information about the study?
F.
Do you volunteer to be in this study of your own free will and without being
pressured by the investigator or study staff?
G.
Do you know that you can leave the study at any time without giving a reason
and with affecting your health care?
H.
Do you know that your records from this study may be reviewed by the study
sponsor and by government authorities?
I.
Do you know that you cannot be in another study while you are in this study?
You must show that you understand what this study involves by correctly answering the five questions 
included in this form. To sign this consent form, you must also be able to answer “Yes” to questions A-I 
listed directly above. 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022
10


Your signature below shows that you have read and understood the information in this document. The 
researchers answered your questions to your satisfaction and you agree to volunteer as a research participant 
for this study. We will give you a copy of this form. 
Printed Name of Adult Study Participant 
Signature of Adult Study Participant 
Date/Time 
Printed Name of Person Explaining Consent Form 
Signature of Person Explaining Consent Form 
Date/Time 
11 
CONSENT FORM (20DEC2021)
Brown University IRB Original Approval: 05/21/2020 
Brown University IRB Amendment Approval: 01/21/2021 
Brown University IRB Amendment Approval: 06/15/2021 
Brown University IRB Amendment Approval: 08/27/2021 
Brown University IRB Amendment Approval: 12/22/2021 
Brown University IRB Amendment Approval: 01/25/2022