Trial Outcomes & Findings for Pilot Study of Entacapone for Methamphetamine Abuse (NCT NCT02058966)

NCT ID: NCT02058966

Last Updated: 2019-09-12

Results Overview

Profile of Mood States is a 65 item questionnaire using a Likert rating scale to assess transient, distinct moods. The questionnaire contains 65 words/statements that describe feelings people have. The test requires you to indicate for each word or statement how you have been feeling in the past week including today. A Total Mood Disturbance score is calculated by adding scores for Tension, Depression, Anger, Fatigue and Confusion and then subtracting the Vigour score. The Total Mood Disturbance scale ranges from -32 to 200 with lower scores indicative of people with more stable mood profiles.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

29 participants

Primary outcome timeframe

Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

Results posted on

2019-09-12

Participant Flow

Study staff screened 80 subjects over the phone between June 2014 to June 2016 at a clinical hospital in Portland, OR.

51 subjects failed the pre-screen primarily due to history of substance use disorder, time commitment conflicts, or unwilling to take methamphetamine. 14 of 29 subjects completed first randomization. Of the 29, 6 declined to participate, 4 did not meet inclusion criteria, 1 was excluded due to an adverse event, and 6 dropped out.

Participant milestones

Participant milestones
Measure	All Subjects Subjects will get either entacapone or placebo, then one hour later, either methamphetamine or placebo. Placebo: capsules compounded to be of similar appearance to the active drugs Entacapone: Entacapone 200 mg oral dose Methamphetamine: Methamphetamine 20 mg oral dose The research pharmacy will assign randomization; they have no contact with the subjects or clinical staff involved in direct subject care so this medication combination could occur at any of the 4 randomization visits.
Open-Label Methamphetamine STARTED	19
Open-Label Methamphetamine Received Methamphetamine	18
Open-Label Methamphetamine COMPLETED	18
Open-Label Methamphetamine NOT COMPLETED	1
First Intervention STARTED	15
First Intervention Received Placebo-Placebo	3
First Intervention Received Placebo-Meth	4
First Intervention Received Entacapone-Placebo	2
First Intervention Received Entacapone-Meth	5
First Intervention COMPLETED	14
First Intervention NOT COMPLETED	1
Second Intervention STARTED	13
Second Intervention Received Placebo-Placebo	2
Second Intervention Received Placebo-Meth	2
Second Intervention Received Entacapone-Placebo	6
Second Intervention Received Entacapone-Meth	3
Second Intervention COMPLETED	13
Second Intervention NOT COMPLETED	0
Third Intervention STARTED	12
Third Intervention Received Placebo-Placebo	4
Third Intervention Received Placebo-Meth	4
Third Intervention Received Entacapone-Placebo	1
Third Intervention Received Entacapone-Meth	3
Third Intervention COMPLETED	12
Third Intervention NOT COMPLETED	0
Fourth Intervention STARTED	12
Fourth Intervention Received Placebo-Placebo	4
Fourth Intervention Received Placebo-Meth	3
Fourth Intervention Received Entacapone-Placebo	3
Fourth Intervention Received Entacapone-Meth	2
Fourth Intervention COMPLETED	12
Fourth Intervention NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	All Subjects Subjects will get either entacapone or placebo, then one hour later, either methamphetamine or placebo. Placebo: capsules compounded to be of similar appearance to the active drugs Entacapone: Entacapone 200 mg oral dose Methamphetamine: Methamphetamine 20 mg oral dose The research pharmacy will assign randomization; they have no contact with the subjects or clinical staff involved in direct subject care so this medication combination could occur at any of the 4 randomization visits.
Open-Label Methamphetamine Adverse Event	1
First Intervention Withdrawal by Subject	1

Baseline Characteristics

Pilot Study of Entacapone for Methamphetamine Abuse

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=12 Participants Participants who completed all four study arms including: 1. Placebo followed by Placebo 2. Placebo followed by Methamphetamine (20 mg) 3. Entacapone (200 mg) followed by Placebo 4. Entacapone (200 mg) followed by Methamphetamine (20 mg)
Age, Continuous	29.1 years STANDARD_DEVIATION 5.12 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

Population: The analysis population includes only the 12 subjects that completed each intervention of the study.

Outcome measures

Outcome measures
Measure	Baseline n=12 Participants Baseline measurements were taking for each subject before drug intervention during each of the 4 visits then averaged over the 4 visits. Baseline measurements reported here are averaged across all subjects.	Placebo Followed by Placebo n=12 Participants Subjects will receive placebo, then one hour later, placebo Placebo: capsules compounded to be of similar appearance to the active drugs	Placebo Followed by Methamphetamine n=12 Participants Subjects will receive placebo, then one hour later, methamphetamine Methamphetamine: Methamphetamine 20 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Placebo n=12 Participants Subjects will receive entacapone, then one hour later, placebo Entacapone: Entacapone 200 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Methamphetamine n=12 Participants Subjects will receive entacapone, then one hour later, methamphetamine Entacapone: Entacapone 200 mg oral dose Methamphetamine: Methamphetamine 20 mg oral dose
Effect of Entacapone on Methamphetamine-induced Mood	12.500 units on a scale Standard Deviation 8.187	13.750 units on a scale Standard Deviation 9.037	7.500 units on a scale Standard Deviation 4.166	9.833 units on a scale Standard Deviation 4.783	8.750 units on a scale Standard Deviation 4.309

PRIMARY outcome

Population: The analysis population includes only the 12 subjects that completed each arm, or intervention, of the study.

The subjective effects of the study drug were evaluated with the Addiction Research Center Inventory (ARCI-49), a 49 item questionnaire consisting of true/false items. True items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. There are 5 subscales: Morphine Benzedrine group scale to measure euphoria (range: 0-16 with higher numbers indicating more euphoria), A Lysergic Acid Diethylamide group scale to estimate dysphoria and agitation (range: 0-14 with higher scores indicating more dysphoria), a Pentobarbital Chlorpromazine Alcohol group scale to measure sedation (range: 0-15 with higher scores indicating more sedation), and a Benzedrine group scale and an Amphetamine Scale to assess stimulant effects (range: 0-13 and 0-11, respectively, with higher scores indicating higher stimulant effects) .

Outcome measures

Outcome measures
Measure	Baseline n=12 Participants Baseline measurements were taking for each subject before drug intervention during each of the 4 visits then averaged over the 4 visits. Baseline measurements reported here are averaged across all subjects.	Placebo Followed by Placebo n=12 Participants Subjects will receive placebo, then one hour later, placebo Placebo: capsules compounded to be of similar appearance to the active drugs	Placebo Followed by Methamphetamine n=12 Participants Subjects will receive placebo, then one hour later, methamphetamine Methamphetamine: Methamphetamine 20 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Placebo n=12 Participants Subjects will receive entacapone, then one hour later, placebo Entacapone: Entacapone 200 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Methamphetamine n=12 Participants Subjects will receive entacapone, then one hour later, methamphetamine Entacapone: Entacapone 200 mg oral dose Methamphetamine: Methamphetamine 20 mg oral dose
Effect of Entacapone on Subjective Effects of Methamphetamine Morphine Benzedrine	1.9375 units on a scale Standard Deviation 2.6610	1.8333 units on a scale Standard Deviation 2.8868	7.9167 units on a scale Standard Deviation 5.9308	2.5833 units on a scale Standard Deviation 4.1000	6.9167 units on a scale Standard Deviation 6.2879
Effect of Entacapone on Subjective Effects of Methamphetamine Lysergic Acid Diethylamide	3.0625 units on a scale Standard Deviation 1.1923	3.25 units on a scale Standard Deviation 1.1382	4.75 units on a scale Standard Deviation 2.0944	3.25 units on a scale Standard Deviation 1.1382	3.8333 units on a scale Standard Deviation 1.3371
Effect of Entacapone on Subjective Effects of Methamphetamine Pentobarbital Chlorpromazine Alcohol	4.8125 units on a scale Standard Deviation 2.5066	5.0000 units on a scale Standard Deviation 2.9233	1.5833 units on a scale Standard Deviation 1.8320	4.0833 units on a scale Standard Deviation 2.8110	2.0000 units on a scale Standard Deviation 2.1320
Effect of Entacapone on Subjective Effects of Methamphetamine Benzedrine	4.9583 units on a scale Standard Deviation 1.4869	5.1667 units on a scale Standard Deviation 2.0817	8.6667 units on a scale Standard Deviation 3.6013	5.3333 units on a scale Standard Deviation 2.1462	7.8333 units on a scale Standard Deviation 3.7376
Effect of Entacapone on Subjective Effects of Methamphetamine Amphetamine	2.0000 units on a scale Standard Deviation 1.8451	2.1667 units on a scale Standard Deviation 2.4802	5.9167 units on a scale Standard Deviation 3.4499	2.5833 units on a scale Standard Deviation 2.6097	5.5833 units on a scale Standard Deviation 4.0104

PRIMARY outcome

Population: The analysis population includes only the 12 subjects that completed each arm, or intervention, of the study.

The Global Rating of Stimulation is a 1-item question "I feel light-headed, restless, or speeded-up" in which the participant is asked to circle one answer on a scale from 0-4, 0 is 'normal', 1 is 'slightly', 2 is 'moderately', 3 is 'very much', and 4 is 'extremely'. Whichever number they circled is their reported score. A higher score is indicative of a greater stimulating effect.

Outcome measures

Outcome measures
Measure	Baseline n=12 Participants Baseline measurements were taking for each subject before drug intervention during each of the 4 visits then averaged over the 4 visits. Baseline measurements reported here are averaged across all subjects.	Placebo Followed by Placebo n=12 Participants Subjects will receive placebo, then one hour later, placebo Placebo: capsules compounded to be of similar appearance to the active drugs	Placebo Followed by Methamphetamine n=12 Participants Subjects will receive placebo, then one hour later, methamphetamine Methamphetamine: Methamphetamine 20 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Placebo n=12 Participants Subjects will receive entacapone, then one hour later, placebo Entacapone: Entacapone 200 mg oral dose Placebo: capsules compounded to be of similar appearance to the active drugs	Entacapone Followed by Methamphetamine n=12 Participants Subjects will receive entacapone, then one hour later, methamphetamine Entacapone: Entacapone 200 mg oral dose Methamphetamine: Methamphetamine 20 mg oral dose
Effect of Entacapone on Methamphetamine-induced Stimulation	0.1667 units on a scale Standard Deviation 0.5586	0.1667 units on a scale Standard Deviation 0.5774	1.4167 units on a scale Standard Deviation 1.1645	0.4167 units on a scale Standard Deviation 0.9003	1.3333 units on a scale Standard Deviation 1.1547

SECONDARY outcome

Population: The analysis population includes only the 12 subjects that completed each arm, or intervention, of the study.

Two computer tests were administered to measure how each medication intervention effects cognitive functioning. The tests administered included the Rapid Visual Information Processing Task (RVIPT), a 6 minute test of sustained attention in which participants are requested to detect target sequences of digits and the Digit Symbol Substitution Task (DSST), a 2 minute test of psychomotor speed and sustained attention consisting of digit-symbol pairs followed by a list of digits where the subject identifies the symbol that corresponds to each digit as fast as possible. The number of correct responses within the allowed time is measured. Higher scores on both tasks indicate better performance.