Topiramate's Effects on Heavy Drinking

NCT02074904 | Terminated Phase 2 Results DMC

• 1 other identifier: TOP MRI
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Drinking

Outcome Measures

Primary Outcomes (1)

• fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure

  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 Outcomes (4)

• Drinking Days

  baseline and 9 weeks

• Change in Gamma-glutamyl Transferase (GGT) or Carbohydrate-deficient Transferrin (CDT) Levels

  baseline and Visit 9 (9 weeks)

• Heavy Drinking Days

  baseline to 9 weeks

• Mean Alcohol Consumption

  baseline to 9 weeks

Study Arms (2)

Topiramate

EXPERIMENTAL

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)

Drug: Topiramate

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Topiramate DRUG

Also known as: Topamax

Topiramate

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania Center for Studies of Addiction

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Alcohol Drinking

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Limitations and Caveats

We terminated the study to run it as a sub-study of NCT02371889. We didn't enter results of the one subject randomized to study medication due to privacy concerns.

Results Point of Contact

• Title: Timothy Pond, MPH
• Organization: UPENN

timpond@pennmedicine.upenn.edu

215-746-1959

Study Officials

• Reagan R Wetherill, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Henry R Kranzler, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2014
• First Posted: February 28, 2014
• Study Start: May 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: September 21, 2018
• Results First Posted: December 11, 2017

Record last verified: 2017-12

Locations

US (1)