Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| P50AA010761 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine whether the catechol-O-methyltransferase (COMT) inhibitor tolcapone, relative to placebo, reduces alcohol drinking and alcohol cue-elicited brain activation and increases brain activation associated with cognitive control as a function of a participant's genotype at a polymorphism in the COMT gene.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo/rs4680 val/val | Placebo Comparator | Placebo three times per day for eight days Individuals with the rs4680 val/val genotype |
|
| Tolcapone/rs4680 val/val | Active Comparator | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype |
|
| Placebo/rs4680 val/met | Placebo Comparator | Placebo three times per day for eight days Individuals with the rs4680 val/met genotype |
|
| Tolcapone/rs4680 val/met | Active Comparator | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype |
|
| Placebo/rs4680 met/met | Placebo Comparator | Placebo three times per day for eight days Individuals with the rs4680 met/met genotype |
|
| Tolcapone/rs4680 met/met |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolcapone | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions | Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method. | Days 1-6 of study medication ingestion |
| Total Number of Drinks Under Controlled Conditions (Bar Lab) | Total number of drinks, out of 8 possible, that participants chose to consume in the bar laboratory after receipt of a priming drink, targeted by sex and body weight to produce a breath alcohol concentration of 0.03 g/dL. Each of the drinks that participants chose to consume was targeted to produce a breath alcohol concentration of 0.015 g/dL. Participants were given a "bar credit" of $16 with which to "purchase" drinks, at the cost of $2/drink, and were told that any money they did not spend would be given to them the following day. | 2 hours during the alcohol challenge procedure |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive-control-associated Brain Activation (fMRI) | Magnitude of change between baseline and day 7 scan in the BOLD signal in the right inferior frontal gyrus to spatial working memory | 7 days--change between baseline and scan on day 7 |
| Alcohol Cue-elicited Brain Activation (fMRI) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29403 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35523943 | Derived | Schacht JP, Yeongbin Im, Hoffman M, Voronin KE, Book SW, Anton RF. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Neuropsychopharmacology. 2022 Oct;47(11):1953-1960. doi: 10.1038/s41386-022-01335-z. Epub 2022 May 6. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Participants were genotyped for the COMT rs4680 single nucleotide polymorphism and subsequently randomized, on the basis of their rs4680 genotype, to take tolcapone or placebo for eight days. Outcomes were the number of standard alcoholic drinks consumed during Days 1-6 ("Natural Drinking Period"), alcohol cue-elicited brain activation on Day 7 ("Neuroimaging"), and the number of drinks, out of 8 possible, that participants chose to self-administer in the lab on Day 8 ("Bar Laboratory").
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/rs4680 Val/Val | Placebo three times per day for eight days Individuals with the rs4680 val/val genotype |
| FG001 | Tolcapone/rs4680 Val/Val | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype |
| FG002 | Placebo/rs4680 Val/Met | Placebo three times per day for eight days Individuals with the rs4680 val/met genotype |
| FG003 | Tolcapone/rs4680 Val/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype |
| FG004 | Placebo/rs4680 Met/Met | Placebo three times per day for eight days Individuals with the rs4680 met/met genotype |
| FG005 | Tolcapone/rs4680 Met/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Natural Drinking Period |
|
| ||||||||||||||||||
| Neuroimaging |
| |||||||||||||||||||
| Bar Laboratory |
|
Non-treatment-seeking individuals between the ages of 21 and 40 with DSM-5 diagnosed Alcohol Use Disorder.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/rs4680 Val/Val | Placebo three times per day for eight days Individuals with the rs4680 val/val genotype |
| BG001 | Tolcapone/rs4680 Val/Val | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions | Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method. | Posted | Mean | Standard Error | standard drinks per day | Days 1-6 of study medication ingestion |
|
8 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo/rs4680 Val/Val | Placebo three times per day for eight days Individuals with the rs4680 val/val genotype |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pregnancy | Pregnancy, puerperium and perinatal conditions | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph P. Schacht, Ph.D. | University of Colorado School of Medicine | (303) 724-3773 | joseph.schacht@cuanschutz.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 11, 2020 | Mar 17, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077867 | Tolcapone |
| ID | Term |
|---|---|
| D001577 | Benzophenones |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Active Comparator |
Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype |
|
| Placebo | Drug |
|
Magnitude of change between baseline and day 7 scan in the right inferior frontal gyrus blood oxygenation level dependent (BOLD) signal to alcohol cues, relative to neutral beverage cues (alcohol cue reactivity task described in Schacht et al., 2013, Neuropsychopharmacology) |
| 7 days--change between baseline and scan on day 7 |
| Lost to Follow-up |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | Placebo/rs4680 Val/Met | Placebo three times per day for eight days Individuals with the rs4680 val/met genotype |
| BG003 | Tolcapone/rs4680 Val/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype |
| BG004 | Placebo/rs4680 Met/Met | Placebo three times per day for eight days Individuals with the rs4680 met/met genotype |
| BG005 | Tolcapone/rs4680 Met/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Placebo/rs4680 Val/Met | Placebo three times per day for eight days Individuals with the rs4680 val/met genotype |
| OG003 | Tolcapone/rs4680 Val/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype |
| OG004 | Placebo/rs4680 Met/Met | Placebo three times per day for eight days Individuals with the rs4680 met/met genotype |
| OG005 | Tolcapone/rs4680 Met/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype |
|
|
|
| Primary | Total Number of Drinks Under Controlled Conditions (Bar Lab) | Total number of drinks, out of 8 possible, that participants chose to consume in the bar laboratory after receipt of a priming drink, targeted by sex and body weight to produce a breath alcohol concentration of 0.03 g/dL. Each of the drinks that participants chose to consume was targeted to produce a breath alcohol concentration of 0.015 g/dL. Participants were given a "bar credit" of $16 with which to "purchase" drinks, at the cost of $2/drink, and were told that any money they did not spend would be given to them the following day. | Due to the COVID-19 pandemic and the need for social distancing, a protocol amendment was required to remove the bar lab procedure. Thus, this outcome was assessed for only the first 63 participants. | Posted | Mean | Standard Error | Drinks | 2 hours during the alcohol challenge procedure |
|
|
|
|
| Other Pre-specified | Cognitive-control-associated Brain Activation (fMRI) | Magnitude of change between baseline and day 7 scan in the BOLD signal in the right inferior frontal gyrus to spatial working memory | Participants who completed both fMRI scans and had usable data | Posted | Mean | Standard Error | Arbitrary units (Day 7 minus Baseline) | 7 days--change between baseline and scan on day 7 |
|
|
|
|
| Other Pre-specified | Alcohol Cue-elicited Brain Activation (fMRI) | Magnitude of change between baseline and day 7 scan in the right inferior frontal gyrus blood oxygenation level dependent (BOLD) signal to alcohol cues, relative to neutral beverage cues (alcohol cue reactivity task described in Schacht et al., 2013, Neuropsychopharmacology) | Participants who completed both fMRI scans and had usable scan data | Posted | Mean | Standard Error | Arbitrary units (Day 7 minus Baseline) | 7 days--change between baseline and scan on day 7 |
|
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 1 |
| 16 |
| EG001 | Tolcapone/rs4680 Val/Val | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype | 0 | 12 | 0 | 12 | 0 | 12 |
| EG002 | Placebo/rs4680 Val/Met | Placebo three times per day for eight days Individuals with the rs4680 val/met genotype | 0 | 17 | 0 | 17 | 0 | 17 |
| EG003 | Tolcapone/rs4680 Val/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype | 0 | 16 | 0 | 16 | 1 | 16 |
| EG004 | Placebo/rs4680 Met/Met | Placebo three times per day for eight days Individuals with the rs4680 met/met genotype | 0 | 15 | 0 | 15 | 0 | 15 |
| EG005 | Tolcapone/rs4680 Met/Met | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype | 0 | 14 | 0 | 14 | 0 | 14 |
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D009596 | Nitrophenols |
| D010636 | Phenols |
| D007659 | Ketones |
| D009574 | Nitro Compounds |
| Mixed Models Analysis |
Linear mixed model testing interaction between medication group and time, controlling for scanner |
| 0.026 |
| Superiority |