Glutamatergic Modulation of Disordered Alcohol Use

Phase 2

Completed

Conditions: Alcohol Dependence

Interventions: Drug: CI-581b
Drug: CI-581a
Behavioral: Motivational Enhancement Therapy (MET)

Registration Number: NCT02539511

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: Alcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinking. Alcohol use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this randomized, double-blind, controlled trial is to test various glutamate modulators in conjunction with motivational enhancement therapy (MET) for alcohol use disorders.

Detailed Description: Individuals diagnosed with alcohol dependence will be randomized to receive a single infusion of glutamate modulators during week 2 while engaged in a 5-week course of MET. They will meet with staff twice weekly, except for week 2 during which they will present to the clinic three times. Clinic visits include MET sessions, psychiatric monitoring, assessments, and study procedures (e.g., medication administration).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Active alcohol dependence. In the case of the use of other drugs, alcohol is designated as the primary drug. At least four heavy drinking day over the past 7 days (>4 drinks a day for males, >3 drinks for females) OR minimum weekly use of 35 drinks for males and 28 for females
Physically healthy
No adverse reactions to study medications
21-69 years of age
Capacity to consent and comply with study procedures, including sufficient proficiency in English
Seeking to reduce or stop alcohol use

Exclusion Criteria

Meets criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance induced psychosis, and current substance-induced mood disorder.
Physiological dependence on another substance requiring medical management, such as opiods or benzodiazepines, excluding caffeine, nicotine, and cannabis
Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders. Significant dissociative symptoms
Current suicide risk or a history of suicide attempt within the past year
Inability to safely initiate 24 hours of abstinence from alcohol; repeated inability to initiate abstinence during the trial without incurring significant withdrawal; history of severe withdrawal phenomena over the past 6 months (e.g., withdrawal-related seizure); or self-reported inability to maintain abstinence for 24 hours without substantial distress.
Pregnant or interested in becoming pregnant during the study period
Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse
Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), leukopenia, active hepatitis or other liver disease with elevated transaminase levels (< 2-3 X upper limit of normal will be considered acceptable if clotting factors are normal), renal failure, epilepsy, or untreated diabetes
Previous history of study medication misuse or abuse, and a history of an adverse reaction/experience with prior exposure to study medications
Recent history of significant violence (past 2 years)
First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
obesity
On psychotropic or other medications whose effect could be disrupted by participation in the study
BMI > 35

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CI-581b+MET	CI-581b	Administration of CI-581b during wk 2 at 0.025 mg/kg in the context of a 5 wk course of MET
CI-581a+MET	CI-581a	Administration of CI-581a during wk 2 at 0.71 mg/kg in the context of a 5 wk course of MET
CI-581a+MET	Motivational Enhancement Therapy (MET)	Administration of CI-581a during wk 2 at 0.71 mg/kg in the context of a 5 wk course of MET
CI-581b+MET	Motivational Enhancement Therapy (MET)	Administration of CI-581b during wk 2 at 0.025 mg/kg in the context of a 5 wk course of MET

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Demonstrating Alcohol Abstinence in the Control (Midazolam) Group Versus the Active (Ketamine) Group	21 days post-infusion	Percentage of participants demonstrating alcohol abstinence in the control (midazolam) group versus the active (ketamine) group

Secondary Outcome Measures