Role of BP1.3656 on Alcohol Responses
Primary Purpose
Alcohol Use Disorder
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
BP1.3656
Placebo
Sponsored by
About this trial
This is an interventional other trial for Alcohol Use Disorder focused on measuring 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
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
Sites / Locations
- Center for Addiction and Mental Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Medication (BP1.3656)
Placebo pills
Arm Description
Participants will receive BP1.3656 in tablet form once daily at a dose of 30 µg/day for the first 4 days, followed by 60 µg/day for the remaining 10 days. If the highest dose is not tolerated, it will be lowered to 30 µg.
Participants will receive matching placebo pills for 14 days.
Outcomes
Primary Outcome Measures
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
Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking placebo.
Breath alcohol concentration (BrAC) test reading will be assessed
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
Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking placebo.
Measured by number of button presses/work sets
Secondary Outcome Measures
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.
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.
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.
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.
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).
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).
Weekly alcohol consumption during treatment with BP1 .3656
Drinks per week, as measured by the Timeline Follow-Back method
Weekly alcohol consumption during treatment with placebo
Drinks per week, as measured by the Timeline Follow-Back method
Full Information
NCT ID
NCT04727086
First Posted
January 19, 2021
Last Updated
April 4, 2023
Sponsor
Centre for Addiction and Mental Health
1. Study Identification
Unique Protocol Identification Number
NCT04727086
Brief Title
Role of BP1.3656 on Alcohol Responses
Official Title
Role of BP1.3656 on Alcohol Responses
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre for Addiction and Mental Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Medication (BP1.3656)
Arm Type
Experimental
Arm Description
Participants will receive BP1.3656 in tablet form once daily at a dose of 30 µg/day for the first 4 days, followed by 60 µg/day for the remaining 10 days. If the highest dose is not tolerated, it will be lowered to 30 µg.
Arm Title
Placebo pills
Arm Type
Placebo Comparator
Arm Description
Participants will receive matching placebo pills for 14 days.
Intervention Type
Drug
Intervention Name(s)
BP1.3656
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered once daily in tablet form.
Primary Outcome Measure Information:
Title
Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking study medication (BP1.3656).
Description
Breath alcohol concentration (BrAC) test reading will be assessed
Time Frame
Measured during one self-administration session in the 2nd week of the 14-day study medication phase.
Title
Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking placebo.
Description
Breath alcohol concentration (BrAC) test reading will be assessed
Time Frame
Measured during one self-administration session in the 2nd week of the 14-day placebo phase.
Title
Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking study medication (BP1.3656).
Description
Measured by number of button presses/work sets
Time Frame
Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day medication phase
Title
Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking placebo.
Description
Measured by number of button presses/work sets
Time Frame
Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day placebo-phase.
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day medication phase.
Title
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)
Description
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.
Time Frame
Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day placebo phase.
Title
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)
Description
8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.
Time Frame
Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of medication phase.
Title
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)
Description
8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.
Time Frame
Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of placebo phase.
Title
Safety and tolerability of BP1.3656
Description
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).
Time Frame
During the free-access and progressive ratio sessions in the 2nd week of the 14-day study medication phase
Title
Safety and tolerability of BP1.3656
Description
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).
Time Frame
During the free-access and progressive ratio sessions in the 2nd week of the 14-day study placebo phase
Title
Weekly alcohol consumption during treatment with BP1 .3656
Description
Drinks per week, as measured by the Timeline Follow-Back method
Time Frame
Measured during the 2nd week of the 14-day study medication phase
Title
Weekly alcohol consumption during treatment with placebo
Description
Drinks per week, as measured by the Timeline Follow-Back method
Time Frame
Measured during the 2nd week of the 14-day placebo phase
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Center for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5S 2S1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Role of BP1.3656 on Alcohol Responses
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