Pilot Study of Entacapone for Methamphetamine Abuse

Study Overview
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Brief Summary
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Addiction to methamphetamine is a serious health problem. There are no medications that a doctor can give someone to help them stop using methamphetamine. Entacapone (Comtan©) is a medication that could help people addicted to methamphetamine. This study will see how entacapone works in healthy people who are given methamphetamine. We think that the study drug will be well tolerated, and that it will prevent some of the effects of methamphetamine that make it so addictive. We also want to see how differences in people's genes may cause differences in the ways the study drug and methamphetamine work for them. The study has six total visits. The first visit is for screening. Tests and procedures will make sure it is safe for subjects to participate. The second visit is a familiarization day. Subjects will receive methamphetamine, but no entacapone. This is done to make sure they can tolerate the drug and recognize its effects before being given a second drug on the same day. Subjects will take surveys and computer tests to see how the medications change mood, thinking, and liking the drug. The final four visits are the actual study days. Subjects will be randomly assigned (like the flip of a coin) to the different ways to get either 1) study medication or placebo (placebo contains no active study medication) and then 2) methamphetamine or placebo. Subjects will be in all four groups during the study, which means that each day a subject will get a different group.

Official Title
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Pilot Study of the Dose Response of Entacapone on Methamphetamine Induced Interest, Mood Elevation, and Reward

Conditions
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Methamphetamine Dependence

Intervention / Treatment
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* Drug: Entacapone
* Drug: Methamphetamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No history of pre-existing physical (including cardiovascular) illness No history of drug abuse or dependence Ability to read and write English Have had at least one exposure to a stimulant (e.g. cocaine, methamphetamine, ecstasy, methylphenidate or any medication in the stimulant class) in their lifetime Exclusion Criteria: Pregnant Taking any psychotropic medication Meeting DSM-IV criteria for active substance abuse or dependence On any stimulant medication History or current hypertension (BP > 140/90 mm Hg) or systolic hypotension (SBP < 90 mm Hg) Subjects with resting pulse rate > 90/min Any active medical illness Family history of abnormal heart rhythms, or sudden cardiac death Subjects who anticipate they may require the emergent use of epinephrine (such as an Epi-Pen®) for the treatment of severe allergic reactions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo followed by Placebo<br>Subjects will receive placebo, then one hour later, placebo | Drug: Placebo<br>* capsules compounded to be of similar appearance to the active drugs<br>|
| Experimental: Placebo followed by Methamphetamine<br>Subjects will receive placebo, then one hour later, methamphetamine | Drug: Methamphetamine<br>* Methamphetamine 20 mg oral dose<br>* Other names: Desoxyn;Drug: Placebo<br>* capsules compounded to be of similar appearance to the active drugs<br>|
| Experimental: Entacapone followed by Placebo<br>Subjects will receive entacapone, then one hour later, placebo | Drug: Entacapone<br>* Entacapone 200 mg oral dose<br>* Other names: Comtam;Drug: Placebo<br>* capsules compounded to be of similar appearance to the active drugs<br>|
| Experimental: Entacapone followed by Methamphetamine<br>Subjects will receive entacapone, then one hour later, methamphetamine | Drug: Entacapone<br>* Entacapone 200 mg oral dose<br>* Other names: Comtam;Drug: Methamphetamine<br>* Methamphetamine 20 mg oral dose<br>* Other names: Desoxyn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Entacapone on Methamphetamine-induced Mood | 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. | 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. | 
| Effect of Entacapone on Subjective Effects of Methamphetamine | 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) . | 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. | 
| Effect of Entacapone on Methamphetamine-induced Stimulation | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Function | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Entacapone, COMT val158met, Methamphetamine