The Role of Brief Potent Glutamatergic Modulation in Addressing Problem Drinking

NCT ID: NCT04084860

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-08
• Study Completion Date: 2024-08-31

Brief Summary

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.

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

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

CI-581a

Intervention Type: DRUG

CI-581a during weeks 1 and 6 at 0.71 mg/kg

MBRP

Intervention Type: BEHAVIORAL

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).

MET

Intervention Type: BEHAVIORAL

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).

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)

Group Type: EXPERIMENTAL

CI-581a

Intervention Type: DRUG

CI-581a during weeks 1 and 6 at 0.71 mg/kg

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)

Group Type: ACTIVE_COMPARATOR

CI-581b

Intervention Type: DRUG

CI-581b during weeks 1 and 6 at 0.0125 mg/kg

MBRP

Intervention Type: BEHAVIORAL

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).

MET

Intervention Type: BEHAVIORAL

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).

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)

Group Type: ACTIVE_COMPARATOR

CI-581b

Intervention Type: DRUG

CI-581b during weeks 1 and 6 at 0.0125 mg/kg

Interventions

CI-581a

CI-581a during weeks 1 and 6 at 0.71 mg/kg

Intervention Type: DRUG

CI-581b

CI-581b during weeks 1 and 6 at 0.0125 mg/kg

Intervention Type: DRUG

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).

Intervention Type: 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).

Intervention Type: BEHAVIORAL

Other Intervention Names

Mindfulness Based Relapse Prevention (MBRP); Motivational Enhancement Therapy (MET)

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Elias Dakwar

Assistant Professor of Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elias Dakwar, MD

Role: PRINCIPAL_INVESTIGATOR

NYSPI/Columbia

Locations

NYSPI

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kate O'Malley

Role: CONTACT

kate.omalley@nyspi.columbia.edu

6467746103 ext. 6103

Elias Dakwar, MD

Role: CONTACT

6467748728 ext. 8728

Facility Contacts

H.O.P.E. Clinic

Role: primary

888-497-8427

Other Identifiers

5R01AA027509-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

7889

Identifier Type: -

Identifier Source: org_study_id