The Role of Brief Potent Glutamatergic Modulation in Addressing Problem Drinking

The Role of Brief Potent Glutamatergic Modulation in Addressing Problem Drinking: a Randomized, Controlled Trial

The proposed project tests the efficacy of glutamate modulators in non-depressed individuals with alcohol use disorder (AUD); the primary hypothesis is that the glutamate modulator being tested reduces heavy drinking days compared to the active control. It also aims to investigate, using a 2 by 2 factorial (2x2) design, the hypothesis that the effects of the glutamate modulator are enhanced when combined with behavioral treatment.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: CI-581a; Behavioral: MBRP; Behavioral: MET; Drug: CI-581b

Detailed Description

Alterations in glutamate neurotransmission are an important target of pharmacotherapy for alcohol use disorder. Our investigations with glutamate modulators in drug and alcohol dependent individuals suggest that they may exert unique therapeutic effects on dependence-related vulnerabilities and may also address problem drinking in alcohol dependent individuals. The proposed project will expand on our prior research by testing the efficacy of glutamate modulators in a larger population of non-depressed individuals with alcohol use disorder (AUD); it also aims to investigate, using a 2 by 2 factorial (2x2) design, the hypothesis that the effects of the glutamate modulator are enhanced when combined with behavioral treatment. It, therefore, has the potential to deepen our understanding of the therapeutic role of glutamate modulators in AUD treatment, as well as to provide further evidence for the efficacy of this novel pharmacotherapy strategy in addressing problem use

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kate O'Malley; Phone Number: 6103 6467746103; Email: kate.omalley@nyspi.columbia.edu
• Study Contact Backup: Name: Elias Dakwar, MD; Phone Number: 8728 6467748728

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • NYSPI
      • Contact: H.O.P.E. Clinic; Phone Number: 888-497-8427
      • Principal Investigator: Elias Dakwar, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Active alcohol use disorder, with at least 4 heavy drinking day over the past 7 days (greater than 4 drinks a day for males, greater than 3 drinks for females). In the case of the use of other drugs, alcohol is designated as the primary drug
2. Physically healthy
3. No adverse reactions to study medications
4. 21-70 years of age
5. Capacity to consent and comply with study procedures, including sufficient proficiency in English
6. Seeking to reduce or stop alcohol use

Exclusion Criteria:

1. Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, or any psychotic illness, including substance-induced psychosis
2. Physiological dependence on another substance, such as opioids or benzodiazepines, excluding caffeine, nicotine, and cannabis
3. Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders
4. Current suicide risk or a history of suicide attempt within the past year
5. Inability to safely initiate 24 hours of abstinence from alcohol, as evidenced by CIWA greater than 10 during screening; history of severe withdrawal phenomena over the past 6 months (e.g., inpatient stabilization, withdrawal-related seizure); or self-reported inability to maintain abstinence for 24 hours.
6. Pregnant or interested in becoming pregnant during the study period
7. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse
8. Unstable physical disorders which might make participation hazardous such as hypertension (>160/90), anemia, active hepatitis or other liver disease (transaminase levels < 2-3 X the upper limit of normal will be considered acceptable), epilepsy, or untreated diabetes. Participants reporting HIV+ status will be asked to provide information about their current treatment, including all medications. Participants who are on the antiretroviral ritonavir (Norvir) will be excluded due to the possibility that study medications in combination with this medication may increase the risk of drug-induced hepatitis.
9. Previous history of misuse or abuse of study medications, and a history of an adverse reaction/experience with prior exposure to study medications
10. Recent history of significant violance
11. On psychotropic or other medications whose effect could be disrupted by participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CI-581a + MET/MBRP; Administration of CI-581a during weeks 1 and 6 at 0.71 mg/kg in the context of a 12 wk outpatient treatment (behavioral treatment combination of MET/MBRP will be provided)	Drug: CI-581a; CI-581a during weeks 1 and 6 at 0.71 mg/kg; Behavioral: MBRP; MBRP will help with maintaining use reduction/abstinence.In this trial, 3 sessions will occur in the first 2 weeks following the second infusion (weeks 6 and 7), while one session a week will be administered in the latter 5 weeks (weeks 8 through 12).; Other Names: Mindfulness Based Relapse Prevention (MBRP); Behavioral: MET; MET may help with goal setting and enhancing engagement with MBRP. In this trial, a standard 5-week MET platform will be provided to individuals randomized to receive behavioral treatment, with an additional session after each infusion (7 sessions total).; Other Names: Motivational Enhancement Therapy (MET)
Experimental: CI-581a + Medication Management; Administration of CI-581a during weeks 1 and 6 at 0.71 mg/kg in the context of a 12 wk outpatient treatment ( no MET/MBRP sessions will be provided, only general check-ins and psychiatrist visits)	Drug: CI-581a; CI-581a during weeks 1 and 6 at 0.71 mg/kg
Active Comparator: CI-581b + MET/MBRP; Administration of CI-581b during weeks 1 and 6 at 0.0125 mg/kg in the context of a 12 wk outpatient treatment (behavioral treatment combination of MET/MBRP will be provided)	Behavioral: MBRP; MBRP will help with maintaining use reduction/abstinence.In this trial, 3 sessions will occur in the first 2 weeks following the second infusion (weeks 6 and 7), while one session a week will be administered in the latter 5 weeks (weeks 8 through 12).; Other Names: Mindfulness Based Relapse Prevention (MBRP); Behavioral: MET; MET may help with goal setting and enhancing engagement with MBRP. In this trial, a standard 5-week MET platform will be provided to individuals randomized to receive behavioral treatment, with an additional session after each infusion (7 sessions total).; Other Names: Motivational Enhancement Therapy (MET); Drug: CI-581b; CI-581b during weeks 1 and 6 at 0.0125 mg/kg
Active Comparator: CI-581b + Medication Management; Administration of CI-581b during weeks 1 and 6 at 0.0125 mg/kg in the context of a 12 wk outpatient treatment (no MET/MBRP sessions will be provided, only general check-ins and psychiatrist visits)	Drug: CI-581b; CI-581b during weeks 1 and 6 at 0.0125 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily occurrence of Heavy Drinking Days (HDD)	Defined as >4 drinks/day for men; >3 drinks for women. Comparing this outcome between groups that receive CI-581a versus CI-581b, as well as between CI-581a groups.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily occurrence of drinking days	Comparing this outcome in between group that received CI-581a versus CI-581b, as well as between CI-581a groups.	12 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Elias Dakwar, MD, NYSPI/Columbia

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 7889 (CTEP); 5R01AA027509-02 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No