Glutamatergic Modulation of Disordered Alcohol Use

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02539511
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 50
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence	Drug: CI-581a; Drug: CI-581b; Behavioral: Motivational Enhancement Therapy (MET)	Phase 2/Phase 3

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Brief Potent Glutamatergic Modulation on Disordered Alcohol Use
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CI-581a+MET Administration of CI-581a during wk 2 at 0.71 mg/kg in the context of a 5 wk course of MET	Drug: CI-581a; Behavioral: Motivational Enhancement Therapy (MET)
Active Comparator: CI-581b+MET Administration of CI-581b during wk 2 at 0.025 mg/kg in the context of a 5 wk course of MET	Drug: CI-581b; Behavioral: Motivational Enhancement Therapy (MET)

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYSPI	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Elias Dakwar, MD, NYSPI/Columbia

Study Documents (Full-Text)

• Study Protocol - Sep 5, 2017
• Statistical Analysis Plan - Sep 5, 2017

More Information

Publications

None provided.

• Responsible Party: Elias Dakwar, Assistant Professor of Clinical Psychiatry, Columbia University
• ClinicalTrials.gov Identifier: NCT02539511
• Other Study ID Numbers: 7014; R21AA023010
• First Posted: Sep 3, 2015
• Last Update Posted: Feb 11, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Alcoholism; Ketamine

Study Results

Participant Flow

Pre-assignment Detail	50 participants were enrolled in the study and from those, 40 were randomized.

Arm/Group Title	Control Group: Midazolam+MET	Active Group: Ketamine+MET
Arm/Group Description	50-minute intravenous infusion of the active control midazolam (0.025 mg/kg), administered during the second week of a five week regimen of motivational enhancement therapy.	50-minute intravenous infusion of ketamine (0.71 mg/kg) administered during the second week of a five week regimen of motivational enhancement therapy.
Period Title: Overall Study
STARTED	23	17
COMPLETED	17	17
NOT COMPLETED	6	0

Baseline Characteristics

Arm/Group Title	Control Group: Midazolam+MET	Active Group: Ketamine+MET	Total
Arm/Group Description	50-minute intravenous infusion of the active control midazolam (0.025 mg/kg), administered during the second week of a five week regimen of motivational enhancement therapy.	50-minute intravenous infusion of ketamine (0.71 mg/kg) administered during the second week of a five week regimen of motivational enhancement therapy.	Total of all reporting groups
Overall Participants	23	17	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (8.3)	50.4 (11.3)	53 (9.8)
Sex: Female, Male (Count of Participants)
Female	14 60.9%	7 41.2%	21 52.5%
Male	9 39.1%	10 58.8%	19 47.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 13%	4 23.5%	7 17.5%
Not Hispanic or Latino	20 87%	13 76.5%	33 82.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	17 100%	40 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Medically healthy, treatment-seeking adults without psychiatric comorbidity and who met DSM-IV criteria for alcohol dependence and minimum use criteria.

Arm/Group Title	Control Group: Midazolam+MET	Active Group: Ketamine+MET
Arm/Group Description	50-minute intravenous infusion of the active control midazolam (0.025 mg/kg), administered during the second week of a five week regimen of motivational enhancement therapy.	50-minute intravenous infusion of ketamine (0.71 mg/kg) administered during the second week of a five week regimen of motivational enhancement therapy.
Measure Participants	23	17
Number [percentage of participants]	68.6 298.3%	98.6 580%

Adverse Events

Time Frame	Adverse event data were collected throughout the study period and at 6 months follow up
Arm/Group Title	Control Group: Midazolam+MET		Active Group: Ketamine+MET
Arm/Group Description	50-minute intravenous infusion of the active control midazolam (0.025 mg/kg), administered during the second week of a five week regimen of motivational enhancement therapy.		50-minute intravenous infusion of ketamine (0.71 mg/kg) vs. 2) administered during the second week of a five week regimen of motivational enhancement therapy.
All Cause Mortality
	Control Group: Midazolam+MET		Active Group: Ketamine+MET
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/17 (0%)
Serious Adverse Events
	Control Group: Midazolam+MET		Active Group: Ketamine+MET
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Control Group: Midazolam+MET		Active Group: Ketamine+MET
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/23 (69.6%)		16/17 (94.1%)
Nervous system disorders
Sedation	12/23 (52.2%)		8/17 (47.1%)
Psychiatric disorders
Mild agitation	0/23 (0%)		2/17 (11.8%)
Vascular disorders
Headache	4/23 (17.4%)		6/17 (35.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.