Role of BP1.3656 on Alcohol Responses

Alcohol Use Disorder Clinical Trial

Official title:

Role of BP1.3656 on Alcohol Responses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04727086
• Other study ID #: 072/2017
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2021
• Est. completion date: August 31, 2022

Study information

• Verified date: April 2023
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 31, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

Drug:
• BP1.3656
BP1.3656 will be administered in tablet form once daily at a dose of 30 µg/day for the first 4 days of the intervention phase, followed by a dose increase to 60 µg/day for the remaining 10 days. If the highest dose is not tolerated, it will be lowered to 30 µg.
• Placebo
Administered once daily in tablet form.

Locations

Country	Name	City	State
Canada	Center for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking study medication (BP1.3656).	Breath alcohol concentration (BrAC) test reading will be assessed	Measured during one self-administration session in the 2nd week of the 14-day study medication phase.
Primary	Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking placebo.	Breath alcohol concentration (BrAC) test reading will be assessed	Measured during one self-administration session in the 2nd week of the 14-day placebo phase.
Primary	Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking study medication (BP1.3656).	Measured by number of button presses/work sets	Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day medication phase
Primary	Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking placebo.	Measured by number of button presses/work sets	Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day placebo-phase.
Secondary	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)	Two subscales (stimulant and sedative) with a 0-10 scoring where higher scores for stimulant subscale indicate increased stimulated effects from alcohol, while higher scores for sedative subscale indicate more sedated effects from alcohol.	Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day medication phase.
Secondary	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)	Two subscales (stimulant and sedative) with a 0-10 scoring where higher scores for stimulant subscale indicate increased stimulation, while higher scores for sedative subscale indicate more sedated effects from alcohol.	Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day placebo phase.
Secondary	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)	8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.	Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of medication phase.
Secondary	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)	8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.	Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of placebo phase.
Secondary	Safety and tolerability of BP1.3656	Side effects of BP1.3656 will be assessed with the Systematic Assessment for Treatment Emergent Effects questionnaire (not reporting score on a scale) and the Pittsburgh Sleep Quality Index (19 items with 0-3 scoring, where higher scores indicate worse sleep quality).	During the free-access and progressive ratio sessions in the 2nd week of the 14-day study medication phase
Secondary	Safety and tolerability of BP1.3656	Side effects of BP1.3656 will be assessed with the Systematic Assessment for Treatment Emergent Effects questionnaire (not reporting score on a scale) and the Pittsburgh Sleep Quality Index (19 items with 0-3 scoring, where higher scores indicate worse sleep quality).	During the free-access and progressive ratio sessions in the 2nd week of the 14-day study placebo phase
Secondary	Weekly alcohol consumption during treatment with BP1 .3656	Drinks per week, as measured by the Timeline Follow-Back method	Measured during the 2nd week of the 14-day study medication phase
Secondary	Weekly alcohol consumption during treatment with placebo	Drinks per week, as measured by the Timeline Follow-Back method	Measured during the 2nd week of the 14-day placebo phase