- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02074904
Topiramate's Effects on Heavy Drinking (TOPMRI)
August 20, 2018 updated by: University of Pennsylvania
Brain Mechanisms of Topiramate's Effects on Heavy Drinking
The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to examine the effects of topiramate on brain and behavioral responses in heavy drinkers to appetitive alcohol reminders (cues that motivate continued alcohol use and relapse).
This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
This project is a double-blind, randomized, placebo-controlled study of topiramate's effects on brain and behavior responses in heavy drinkers.
Eligible volunteers who meet study criteria will be randomized to receive either topiramate or placebo with weekly visits and medication management sessions.
Participants will complete two magnetic resonance imaging sessions.
The first scan session will occur prior to starting study drug, and the second scan will occur following six weeks of study drug.
This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Center for Studies of Addiction
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Physically healthy, as determined by a comprehensive physical examination and approval of the study physician, males or females who drink alcohol, ages 18-60.
- Average weekly ethanol consumption of >24 standard drinks for men, or >18 standard drinks for women.
- Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 2 years postmenopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include: the birth control pill, intrauterine device, injection of Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier methods (such as condoms and diaphragm/spermicide), male partner sterilization, abstinence (and agreement to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence), and tubal ligation.
- Provide voluntary informed consent.
- Must be able to read. [Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.]
- Intelligence quotient of ≥ 80.
Exclusion Criteria:
- Current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation.
- History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
- Current major DSM-IV Axis I diagnoses other than alcohol use disorder (except nicotine use disorder).
- Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
- History of a serious psychiatric illness including psychosis, bipolar disorder, or suicidal or homicidal intent.
- Current treatment with carbonic anhydrase inhibitors.
- Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
- Current regular treatment with psychotropic medications (e.g., benzodiazepines, antidepressants), which affect neurotransmitter systems or a medication being used to treat alcohol use disorders (e.g., naltrexone, acamprosate).
- Vision problems that cannot be corrected with glasses.
- Body Mass Index (BMI) greater than or equal to 34, body girth greater than 52 inches and a head girth greater than 25 inches.
- History of stroke and/or stroke related spasticity.
- History of glaucoma or kidney stones.
- HIV positive.
- History of seizures.
- History of topiramate treatment for alcohol use disorder and report no treatment response.
- Current DSM-5 diagnosis of alcohol use disorder that is clinically too severe to permit them to participate in a research trial in which the goal is to stop or reduce drinking.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
placebo
|
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Experimental: Topiramate
up to 200mg/day orally (over 8 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)
|
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure
Time Frame: baseline to after 6 weeks of study drug
|
At baseline (prior to randomization), brain and behavioral responses will be significantly greater during alcohol cue exposure compared to non-alcohol cue exposure.
Following 6 weeks of study drug, individuals receiving topiramate will demonstrate greater reductions in brain activity and drinking behavior compared to individuals receiving placebo.
Individuals receiving placebo will exhibit responses similar to baseline responses.
|
baseline to after 6 weeks of study drug
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Drinking Days
Time Frame: baseline and 9 weeks
|
change in drinking days from baseline to 9 weeks
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baseline and 9 weeks
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Change in Gamma-glutamyl Transferase (GGT) or Carbohydrate-deficient Transferrin (CDT) Levels
Time Frame: baseline and Visit 9 (9 weeks)
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Change in gamma-glutamyl transferase (GGT) or carbohydrate-deficient transferrin (CDT) levels after 9 weeks of treatment.
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baseline and Visit 9 (9 weeks)
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Heavy Drinking Days
Time Frame: baseline to 9 weeks
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change in number of heavy drinking days from baseline to 9 weeks
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baseline to 9 weeks
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Mean Alcohol Consumption
Time Frame: baseline to 9 weeks
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change in mean alcohol consumption from baseline to 9 weeks
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baseline to 9 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Reagan R Wetherill, PhD, University of Pennsylvania
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2015
Primary Completion (Actual)
March 1, 2017
Study Completion (Actual)
March 1, 2017
Study Registration Dates
First Submitted
February 20, 2014
First Submitted That Met QC Criteria
February 26, 2014
First Posted (Estimate)
February 28, 2014
Study Record Updates
Last Update Posted (Actual)
September 21, 2018
Last Update Submitted That Met QC Criteria
August 20, 2018
Last Verified
December 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TOP MRI
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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