Topiramate's Effects on Heavy Drinking

Brain Mechanisms of Topiramate's Effects on Heavy Drinking

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02074904

Acronym

TOPMRI

Enrollment

Registered

2014-02-28

Start date

2015-05-31

Completion date

2017-03-31

Last updated

2018-09-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Drinking

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.

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.

Interventions

DRUGTopiramate

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure	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.

Secondary

Measure	Time frame	Description
Drinking Days	baseline and 9 weeks	change in drinking days from baseline to 9 weeks
Change in Gamma-glutamyl Transferase (GGT) or Carbohydrate-deficient Transferrin (CDT) Levels	baseline and Visit 9 (9 weeks)	Change in gamma-glutamyl transferase (GGT) or carbohydrate-deficient transferrin (CDT) levels after 9 weeks of treatment.
Heavy Drinking Days	baseline to 9 weeks	change in number of heavy drinking days from baseline to 9 weeks
Mean Alcohol Consumption	baseline to 9 weeks	change in mean alcohol consumption from baseline to 9 weeks

Countries

United States

Participant flow

Participants by arm

Arm	Count
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) Topiramate	0
Placebo placebo Placebo	0
Total	0

Baseline characteristics

Characteristic	—
Region of Enrollment United States	— participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 0
other Total, other adverse events	0 / 1	0 / 0
serious Total, serious adverse events	0 / 1	0 / 0

Outcome results

Primary

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.

Time frame: baseline to after 6 weeks of study drug