The Role of Brief Potent Glutamatergic Modulation in Addressing Problem Drinking

New York State Psychiatric Institute

Status and phase: Enrolling; Phase 2

Conditions: Alcohol Use Disorder

Treatments: Behavioral: MBRP; Drug: CI-581b; Behavioral: MET; Drug: CI-581a

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04084860

7889 (Other Identifier)

5R01AA027509-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 120 estimated patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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120 participants in 4 patient groups

CI-581a + MET/MBRP

Experimental group

Description:

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)

Treatment:

Drug: CI-581a

Behavioral: MET

Behavioral: MBRP

CI-581a + Medication Management

Experimental group

Description:

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)

Treatment:

Drug: CI-581a

CI-581b + MET/MBRP

Active Comparator group

Description:

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)

Treatment:

Behavioral: MET

Drug: CI-581b

Behavioral: MBRP

CI-581b + Medication Management

Active Comparator group

Description:

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)

Treatment:

Drug: CI-581b