Trial Outcomes & Findings for Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control (NCT NCT02949934)

Last Updated: 2023-06-09

Results Overview

Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Days 1-6 of study medication ingestion

Results posted on

2023-06-09

Participant Flow

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").

Participant milestones

Participant milestones
Measure	Placebo/rs4680 Val/Val Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	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	Placebo/rs4680 Val/Met Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	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	Placebo/rs4680 Met/Met Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	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
Natural Drinking Period STARTED	16	12	17	16	15	14
Natural Drinking Period COMPLETED	15	12	17	15	14	14
Natural Drinking Period NOT COMPLETED	1	0	0	1	1	0
Neuroimaging STARTED	15	12	17	15	14	14
Neuroimaging COMPLETED	12	12	15	15	12	12
Neuroimaging NOT COMPLETED	3	0	2	0	2	2
Bar Laboratory STARTED	13	12	17	15	13	14
Bar Laboratory COMPLETED	12	7	10	11	7	13
Bar Laboratory NOT COMPLETED	1	5	7	4	6	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/rs4680 Val/Val Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	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	Placebo/rs4680 Val/Met Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	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	Placebo/rs4680 Met/Met Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	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
Natural Drinking Period Adverse Event	1	0	0	1	0	0
Natural Drinking Period Lost to Follow-up	0	0	0	0	1	0
Neuroimaging Protocol Violation	2	0	0	0	1	0
Neuroimaging Motion artifacts in imaging data	1	0	1	0	1	0
Neuroimaging Not scanned	0	0	1	0	0	2
Bar Laboratory Procedure not done due to COVID-19 pandemic	0	5	5	3	5	1
Bar Laboratory Adverse Event	1	0	2	0	1	0
Bar Laboratory Protocol Violation	0	0	0	1	0	0

Baseline Characteristics

Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/rs4680 Val/Val n=16 Participants Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	Tolcapone/rs4680 Val/Val n=12 Participants 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 n=17 Participants Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	Tolcapone/rs4680 Val/Met n=16 Participants 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 n=15 Participants Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	Tolcapone/rs4680 Met/Met n=14 Participants 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	Total n=90 Participants Total of all reporting groups
Age, Continuous	26.9 years STANDARD_DEVIATION 5.5 • n=5 Participants	29.3 years STANDARD_DEVIATION 4.7 • n=7 Participants	25.7 years STANDARD_DEVIATION 4.7 • n=5 Participants	26.3 years STANDARD_DEVIATION 5.0 • n=4 Participants	26.3 years STANDARD_DEVIATION 5.2 • n=21 Participants	25.3 years STANDARD_DEVIATION 5.7 • n=10 Participants	26.5 years STANDARD_DEVIATION 5.1 • n=115 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	9 Participants n=10 Participants	37 Participants n=115 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants	10 Participants n=4 Participants	9 Participants n=21 Participants	5 Participants n=10 Participants	53 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	4 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	7 Participants n=115 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants	14 Participants n=4 Participants	15 Participants n=21 Participants	12 Participants n=10 Participants	79 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Region of Enrollment United States	16 participants n=5 Participants	12 participants n=7 Participants	17 participants n=5 Participants	16 participants n=4 Participants	15 participants n=21 Participants	14 participants n=10 Participants	90 participants n=115 Participants

PRIMARY outcome

Timeframe: Days 1-6 of study medication ingestion

Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.

Outcome measures

Outcome measures
Measure	Placebo/rs4680 Val/Val n=15 Participants Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	Tolcapone/rs4680 Val/Val n=12 Participants 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 n=17 Participants Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	Tolcapone/rs4680 Val/Met n=15 Participants 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 n=14 Participants Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	Tolcapone/rs4680 Met/Met n=14 Participants 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
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions	6.018 standard drinks per day Standard Error 0.586	3.534 standard drinks per day Standard Error 0.668	3.998 standard drinks per day Standard Error 0.538	5.012 standard drinks per day Standard Error 0.567	5.271 standard drinks per day Standard Error 0.596	5.949 standard drinks per day Standard Error 0.602

PRIMARY outcome

Timeframe: 2 hours during the alcohol challenge procedure

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo/rs4680 Val/Val n=14 Participants Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	Tolcapone/rs4680 Val/Val n=7 Participants 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 n=10 Participants Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	Tolcapone/rs4680 Val/Met n=11 Participants 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 n=8 Participants Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	Tolcapone/rs4680 Met/Met n=13 Participants 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
Total Number of Drinks Under Controlled Conditions (Bar Lab)	5.353 Drinks Standard Error 0.721	3.256 Drinks Standard Error 0.955	5.01 Drinks Standard Error 0.812	4.964 Drinks Standard Error 0.752	1.68 Drinks Standard Error 0.935	4.732 Drinks Standard Error 0.704

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days--change between baseline and scan on day 7

Population: Participants who completed both fMRI scans and had usable data

Magnitude of change between baseline and day 7 scan in the BOLD signal in the right inferior frontal gyrus to spatial working memory

Outcome measures

Outcome measures
Measure	Placebo/rs4680 Val/Val n=11 Participants Placebo three times per day for eight days Individuals with the rs4680 val/val genotype	Tolcapone/rs4680 Val/Val n=12 Participants 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 n=15 Participants Placebo three times per day for eight days Individuals with the rs4680 val/met genotype	Tolcapone/rs4680 Val/Met n=14 Participants 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 n=12 Participants Placebo three times per day for eight days Individuals with the rs4680 met/met genotype	Tolcapone/rs4680 Met/Met n=11 Participants 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
Cognitive-control-associated Brain Activation (fMRI)	-0.196 Arbitrary units (Day 7 minus Baseline) Standard Error .086	-0.063 Arbitrary units (Day 7 minus Baseline) Standard Error .082	-0.178 Arbitrary units (Day 7 minus Baseline) Standard Error .074	0.076 Arbitrary units (Day 7 minus Baseline) Standard Error .076	-0.017 Arbitrary units (Day 7 minus Baseline) Standard Error .082	-0.224 Arbitrary units (Day 7 minus Baseline) Standard Error .086

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days--change between baseline and scan on day 7

Population: Participants who completed both fMRI scans and had usable scan data

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)