Treatment for Alcohol Dependence With Gabapentin

NCT02771925 | Terminated Phase 4 DMC

• 1 other identifier: TAG2016
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorders are present across medical specialties, with alcohol-related deaths particularly prevalent in the categories of injury, liver cirrhosis, cancer, cardiovascular disease, disorders of the peripheral nerves and of the central nervous system. Alcohol dependence, also referred to as alcohol use disorder, is a chronic, relapsing disorder marked by compulsive alcohol use, an inability to stop drinking despite harmful consequences, and the emergence of a withdrawal syndrome upon cessation of use. Early abstinence is associated with activation of brain stress systems in the extended amygdala. Clinically, protracted abstinence involves symptoms of craving, mood and sleep disturbance, all of which have been identified as risk factors for relapse. Nonetheless, implementation of alcohol-specific medications remains limited across most medical specialties. Medications for treating alcohol dependence primarily have been adjunctive interventions, and only three medications-disulfiram, naltrexone, and acamprosate-are approved for this indication by the United States Food and Drug Administration. Baclofen, an inhibitor of synaptic transmission through spinal reflex arcs via hyper polarization of primary afferent fiber terminals, was originally approved by the Food and Drug Administration in 1977 for use in spasticity associated with neurologic conditions, such as multiple sclerosis and spinal cord lesions. However, due to its pharmacologic properties it has also been investigated for the treatment of alcohol dependence. But in the clinical practice of study physicians, it was observed that most of the patients who were prescribed baclofen for alcohol dependence hit back to alcohol very soon despite being on the drug. Therefore there is a need to search for an alternative drug which could be beneficial for this population of patients. Gabapentin is Food and Drug Administration-approved for the management of epileptic seizures and neuropathic pain. It is believed to act by blocking a specific alpha-2d subunit of the voltage-gated calcium channel at selective presynaptic sites and, as a result, to indirectly modulate Gamma Butyric Acid neurotransmission. Pre-clinical findings indicate that gabapentin normalizes the stress-induced Gamma Butyric Acid activation in the amygdala that is associated with alcohol dependence, and provide an excellent pre-clinical rationale for evaluating gabapentin as a treatment for alcohol dependence. Earlier studies of gabapentin in alcohol dependent subjects, attempting to abstain following withdrawal support the safety and potential efficacy of gabapentin in alcohol dependent patients, but definitive conclusions were limited by either small sample size, methodological, or dosing issues.

Conditions

Alcohol Dependence

Keywords

Gabapentin; Alcohol Dependence

Outcome Measures

Primary Outcomes (1)

• Rate of no Heavy Episodic Drinking over 6 month.

  (Pattern of reduced drinking, described as no heavy episodic drinking. Heavy episodic drinking days are defined by the FDA - National Institute on Alcohol Abuse and Alcoholism (NIAAA) as days when the patient consumes more than four standard drinks (men) or more than three standard drinks (women). Responder analysis will be applied to the rate of Heavy Episodic Drinking.

  6 month

Secondary Outcomes (5)

• Alcohol Craving

  6 month

• Change in Quality of Life

  6 month

• Change in sleep pattern

  6 month

• Rate of Hospital Admission due to alcohol abuse/ decompensation of liver disease

  6 month

• Change in Gamma-Glutamyl Transferase (GGT) level over the 6 month period

  6 month

Study Arms (2)

gabapentin

EXPERIMENTAL

Total subjects 100 (Alcoholic liver disease:Alcoholics with no liver disease= 1:1) each will receive Gabapentin 2g/day divided in two doses for 24 weeks All patient will receive standard of care treatment

Drug: Gabapentin 2g/day divided in two doses for 24 weeks

Placebo

PLACEBO COMPARATOR

Total subjects 100 (Alcoholic liver disease: Alcoholics with no liver disease= 1:1)) each will receive Placebo 2g/day divided in two doses for 24 weeks All patient will receive standard of care treatment

Drug: Placebo 2g/day divided in two doses for 24 weeks

Interventions

Gabapentin 2g/day divided in two doses for 24 weeks DRUG

Total subjects 100 (Alcoholic liver disease:Alcoholics with no liver disease= 1:1) each will receive Gabapentin 2000mg/day divided in two doses for 24 weeks. All patients will receive standard of care treatment.

Also known as: Gabapentin

gabapentin

Placebo 2g/day divided in two doses for 24 weeks DRUG

Total subjects 100 (Alcoholic liver disease: Alcoholics with no liver disease= 1:1)) each will receive Placebo 2000mg/day divided in two doses for 24 weeks. All patients will receive standard of care treatment. Concurrent with study medication, study clinicians will provide participants with 20 minutes of weekly manual-guided counseling designed to increase motivation, abstinence, and medication compliance.

Also known as: Starch

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age more then 18 years
• Meet the Diagnostic and Statistical Manual-Fourth Edition (DSM-V) criteria for current alcohol dependence

You may not qualify if:

• Risk for significant withdrawal based on a Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-AR) score \>9
• More than one month of abstinence
• Dependence on substances other than alcohol
• A urine drug screen positive for benzodiazepines or opiates
• Clinically significant medical or psychiatric disorders treatment with medications that could affect study outcomes
• Treatment mandated by a legal authority

Sponsors & Collaborators

• Dayanand Medical College and Hospital: lead

Study Sites (1)

Dyanand Medical College and Hospital

Ludhiana, Punjab, 141001, India

Location

Related Publications (5)

• Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):70-7. doi: 10.1001/jamainternmed.2013.11950.

  PMID: 24190578 RESULT

• Williams SH. Medications for treating alcohol dependence. Am Fam Physician. 2005 Nov 1;72(9):1775-80.

  PMID: 16300039 RESULT

• Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009 Jun 27;373(9682):2223-33. doi: 10.1016/S0140-6736(09)60746-7.

  PMID: 19560604 RESULT

• Mark TL, Kassed CA, Vandivort-Warren R, Levit KR, Kranzler HR. Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty. Drug Alcohol Depend. 2009 Jan 1;99(1-3):345-9. doi: 10.1016/j.drugalcdep.2008.07.018. Epub 2008 Sep 25.

  PMID: 18819759 RESULT

• Koob GF. A role for brain stress systems in addiction. Neuron. 2008 Jul 10;59(1):11-34. doi: 10.1016/j.neuron.2008.06.012.

  PMID: 18614026 RESULT

MeSH Terms

Conditions

Alcoholism

Interventions

Gabapentin; Starch

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• Sandeep S Sidhu, DM

  Dayanand Medical College and Hospital, Ludhiana, Punjab, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Department of Gastroenterology

Study Record Dates

• First Submitted: April 18, 2016
• First Posted: May 13, 2016
• Study Start: June 1, 2016
• Primary Completion: April 23, 2018
• Study Completion: May 16, 2018
• Last Updated: February 13, 2020

Record last verified: 2020-02

Locations

IN (1)