Gabapentin for Bipolar & Cannabis Use Disorders

• ClinicalTrials.gov Identifier: NCT03334721
• Recruitment Status: Completed
• First Posted: November 7, 2017
• Results First Posted: November 13, 2020
• Last Update Posted: November 13, 2020
• Sponsor: Medical University of South Carolina
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): James J. Prisciandaro, Medical University of South Carolina

Study Description

Brief Summary:

The proposed 2-week, double-blind, crossover, proof of concept study aims to measure and manipulate core neurochemical (i.e., dysregulated brain GABA/glutamate homeostasis) and neurobehavioral (i.e., elevated impulsivity) dysfunctions characteristic of individuals with cannabis use disorder (CUD) and Bipolar Disorder (BD), using a medication that has been shown to increase cortical GABA (i.e., gabapentin) levels in past research, and to evaluate medication-related changes in response inhibition (go no-go) and cannabis cue reactivity functional Magnetic Resonance Imaging tasks, as well as cannabis use, mood symptoms (including anxiety and sleep), and impulsivity in individuals with CUD+BD.

Condition or disease	Intervention/treatment	Phase
Bipolar I Disorder; Bipolar II Disorder; Cannabis Use Disorder; Substance Use Disorders	Drug: Gabapentin; Drug: Placebo Oral Capsule	Phase 2

Detailed Description:

Bipolar disorder (BD) is the Axis I condition most strongly associated with cannabis use disorder (CUD); there is a six-fold increase in the prevalence of CUD in individuals with BD relative to the general population. Individuals with co-occurring CUD and BD (CUD+BD) have substantially worse clinical outcomes than those with either BD or CUD alone. Response to mood stabilizing medications appears to be poor, yet little is known about optimal treatment for CUD+BD, as there have been no randomized medication trials for CUD+BD to date. Convergent evidence supports dysregulated brain γ-Aminobutyric acid (GABA)/glutamate homeostasis as a candidate target for pharmacological intervention in CUD+BD. Preclinical and clinical studies have demonstrated that CUD and BD are each associated with prefrontal GABA and glutamate disturbances and that impulsivity, a core neurobehavioral feature of both CUD and BD and a key Research Domain Criteria (RDoC) construct, is causally related to GABAergic/glutamatergic functioning. Gabapentin has been consistently shown in preclinical research to modulate GABA and glutamate transmission. In human Proton Magnetic Resonance Spectroscopy (1H-MRS) studies, both acute and chronic gabapentin dosing have been shown to increase brain GABA levels, however, few studies have investigated gabapentin effects on glutamate levels. Researchers propose that gabapentin may impact clinical outcomes in CUD+BD individuals both directly and indirectly through their impact on impulsivity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Gabapentin for Bipolar & Cannabis Use Disorders
• Actual Study Start Date: October 1, 2017
• Actual Primary Completion Date: July 1, 2019
• Actual Study Completion Date: July 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gabapentin, Then Placebo Oral Capsule; Week 1: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Week 2: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7).	Drug: Gabapentin; 5 day trial of gabapentin with titration to 1,200mg; Drug: Placebo Oral Capsule; 5 day trial of matched placebo
Experimental: Placebo Oral Capsule, Then Gabapentin; Week 1: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Week 2: 1-week condition will consist of an in-person study visit for assessment and dispensing of Gabapentin medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (days 1-5), MRI (Day 5), and medication washout (Days 5-7).	Drug: Gabapentin; 5 day trial of gabapentin with titration to 1,200mg; Drug: Placebo Oral Capsule; 5 day trial of matched placebo

Outcome Measures

Primary Outcome Measures :

1. Prefrontal GABA Concentrations Through Proton Magnetic Resonance Spectroscopy [ Time Frame: Day 5 of each experimental condition ]
   Concentrations of GABA, normalized to water and corrected for CSF%, in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meets DSM-V criteria for Bipolar Disorder
• Meets DSM-V criteria for Cannabis Use Disorder
• Using at least one mood stabilizing medication

Exclusion Criteria:

• Serious medical or non-inclusionary psychiatric disease
• Concomitant use of benzodiazepine medications or any medications hazardous if taken with gabapentin
• History of clinically significant brain injury
• Presence of non-MRI safe material, or clinically significant claustrophobia.

Contacts and Locations

Locations

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: James J Prisciandaro, PhD; Medical University of South Carolina

  Study Documents (Full-Text)

Documents provided by James J. Prisciandaro, Medical University of South Carolina:

Study Protocol and Statistical Analysis Plan  [PDF] October 25, 2017

More Information

• Responsible Party: James J. Prisciandaro, Assistant Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT03334721
• Other Study ID Numbers: 69905; R21DA04391701A1 ( Other Grant/Funding Number: NIDA )
• First Posted: November 7, 2017
• Results First Posted: November 13, 2020
• Last Update Posted: November 13, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Disease; Marijuana Abuse; Substance-Related Disorders; Pathologic Processes; Chemically-Induced Disorders; Mental Disorders; Gabapentin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents