Clinical trial NCT04727086: Role of BP1.3656 on Alcohol Responses
Official title: Role of BP1.3656 on Alcohol Responses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Use Disorder
Keywords: Ethanol
Alcohol
Self administration
BP1.3656B
Alcohol Use Disorder
Alcoholism
Alcohol Drinking
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2021-01-27
Enrollment: 37
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be a within-subjects, counterbalanced, crossover trial with a washout period. Participants will receive either placebo or the interventional drug BP1.3656 during the initial 14-day phase of the study and receive the other intervention during the second 14-day phase of the study. The washout period will last a minimum of 14 days.

Participants will come in to the laboratory on two separate days near the end of each intervention phase to complete alcohol self-administration sessions.
Primary purpose: OTHER

Brief summary: The current study will determine whether a novel pharmacotherapy, BP1. 3656, affects laboratory alcohol self-administration in participants with alcohol use disorder (AUD).

Detailed description: The current study employs BP1.3656, a novel investigational compound with a track record for safety and tolerability in phase I clinical trials. When administered to mice, BP1.3656 was associated with increased metabolism of histamine and elevated brain dopamine and acetylcholine, suggestive of utility in psychiatric disorders including Alcohol Use Disorder (AUD).

This study is a Phase II laboratory-based trial of BP1 .3656 for AUD. 40 non-treatment seeking participants with AUD will be recruited. Participants will be randomly assigned to intervention with BP1 .3656 or placebo in a within-subject, crossover design. During each intervention period, outcome measures relating to alcohol motivation and self-administration will be assessed in the laboratory. It is hypothesized that relative to placebo, alcohol self-administration will be decreased by BP1 .3656.

Eligibility criteria: Inclusion Criteria:

* Fulfilling Diagnostic and Statistical Manual (DSM)-5 criteria for AUD with endorsement of 4-8 symptoms
* Average weekly consumption ≥ 14 standard drinks for women and ≥ 21 standard drinks for men over the past 3 months
* Willingness to take study medication and participate in laboratory sessions requiring alcohol administration
* Able to give written informed consent
* Certified as healthy by a comprehensive clinical assessment. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels should not be more than 1.2 times normal

Exclusion Criteria:

* Seeking treatment for alcohol use (or current efforts to cut down or seek treatment)
* A Clinical Institute Withdrawal Assessment (CIWA) score of 8+ upon initial assessment
* Current medical conditions or medications that contraindicate receiving the study drug (based on the study physician's assessment)
* Meeting criteria for a current substance use disorder aside from alcohol or nicotine
* Recent recreational drug use (assessed via urine toxicology screen)
* History of gross psychiatric or neurological impairment (e.g., schizophrenia, bipolar disorder, neurological disorders)
* Reported difficulty with intravenous procedures
* Self-report of significant alcohol-induced flushing after 1-2 drinks (a proxy for aldehyde dehydrogenase deficiency)
* Currently nursing or pregnant (females)
* Serious unstable medical condition
* Current use of medication that could increase the risk of BP1.3656B administration
* Having any clinical condition, drug sensitivity, or prior therapy which, in the investigator's opinion, makes the participant unsuitable for the study
* Any history of seizures

Primary outcomes:
measure: Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking study medication (BP1.3656).
timeFrame: Measured during one self-administration session in the 2nd week of the 14-day study medication phase.
measure: Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking placebo.
timeFrame: Measured during one self-administration session in the 2nd week of the 14-day placebo phase.
measure: Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking study medication (BP1.3656).
timeFrame: Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day medication phase
measure: Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking placebo.
timeFrame: Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day placebo-phase.
Secondary outcomes:
measure: Subjective effects of alcohol during free-access and progressive ratio self-administration sessions while taking study medication (BP1.3656), as measured by the Biphasic Alcohol Effects Scale (0-10 scoring)
timeFrame: Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day medication phase.
measure: Subjective effects of alcohol (maximum reported stimulation and sedation from alcohol) during free-access and progressive ratio self-administration sessions while taking placebo, as measured by the Biphasic Alcohol Effects Scale (0-10 scoring)
timeFrame: Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day placebo phase.
measure: Self-reported craving after a priming dose of alcohol during free-access and progressive ratio self-administration sessions while taking BP1.3656, as measured by the Alcohol Urge Questionnaire (1-7 scoring)
timeFrame: Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of medication phase.
measure: Self-reported craving after a priming dose of alcohol during free-access and progressive ratio self-administration sessions while taking placebo, as measured by the Alcohol Urge Questionnaire (1-7 scoring)
timeFrame: Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of placebo phase.
measure: Safety and tolerability of BP1.3656
timeFrame: During the free-access and progressive ratio sessions in the 2nd week of the 14-day study medication phase
measure: Safety and tolerability of BP1.3656
timeFrame: During the free-access and progressive ratio sessions in the 2nd week of the 14-day study placebo phase
measure: Weekly alcohol consumption during treatment with BP1 .3656
timeFrame: Measured during the 2nd week of the 14-day study medication phase
measure: Weekly alcohol consumption during treatment with placebo
timeFrame: Measured during the 2nd week of the 14-day placebo phase
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Center for Addiction and Mental Health
state: Ontario
Study officials:
References: