Methamphetamine DependenceEarly Phase 1NCT02058966

Pilot Study of Entacapone for Methamphetamine Abuse

A Early Phase 1 study testing Entacapone and Methamphetamine in people with Methamphetamine Dependence, run by Oregon Health and Science University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Methamphetamine Dependence
What is being tested?: Entacapone and Methamphetamine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 1 siteUnited States
Study dates: Jun 2014to Jun 2016
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Oregon Health & Science University
Portland, Oregon, 97239

Other trials in United States

About this study

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

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.

Conditions: Methamphetamine Dependence
Being tested: Entacapone, Methamphetamine, Placebo
Keywords: Entacapone, COMT val158met, Methamphetamine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EntacaponeDrug
Also called Comtam
Entacapone 200 mg oral dose
MethamphetamineDrug
Also called Desoxyn
Methamphetamine 20 mg oral dose
PlaceboDrug
capsules compounded to be of similar appearance to the active drugs

Study groups in NCT02058966
Study group	Role	What they receive
Placebo followed by Placebo	Placebo comparator	Subjects will receive placebo, then one hour later, placebo Receives: Drug: Placebo
Placebo followed by Methamphetamine	Experimental	Subjects will receive placebo, then one hour later, methamphetamine Receives: Drug: Methamphetamine; Drug: Placebo
Entacapone followed by Placebo	Experimental	Subjects will receive entacapone, then one hour later, placebo Receives: Drug: Entacapone; Drug: Placebo
Entacapone followed by Methamphetamine	Experimental	Subjects will receive entacapone, then one hour later, methamphetamine Receives: Drug: Entacapone; Drug: Methamphetamine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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) .
Measured: 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.
Measured: 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 outcomes (1)

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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2014Jun 2016

First posted11 Feb 2014 (estimated)
Study startJun 2014
Primary completionJun 2016
Study completionJun 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Methamphetamine DependenceStudies of the same condition, open and under way.
More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02058966
Sponsor's protocol ID: 8874
Other IDs: 1004805, 3986
Status last verified: Sep 2019
First submitted: 5 Feb 2014
Last updated: 12 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Human Stress Response in a Simulated ED Setting
Stress Physiology, Stress Reaction
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rTMS for Craving in Methamphetamine Use Disorder
Methamphetamine Abuse, Substance Use Disorders
Active, not recruitingPhase 3
Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder
Methamphetamine-dependence, Methamphetamine Abuse
RecruitingPhase 2
Glutide for Ending Methamphetamine
Methamphetamine-dependence
RecruitingPhase 2
Feasibility of Long-term, High-dose Stimulant for Methamphetamine Use Disorder
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All Methamphetamine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of the Dose Response of Entacapone on Methamphetamine Induced Interest, Mood Elevation, and Reward
ClinicalTrials.gov ID: NCT02058966
Acronym / sponsor ID: 8874
Conditions: Methamphetamine Dependence
Keywords: Entacapone, COMT val158met, Methamphetamine
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Oregon Health and Science UniversityUniversity, hospital or other
Collaborators: Portland VA Medical Center
Study start: Jun 2014
Primary completion: Jun 2016 (actual)
Study completion: Jun 2016 (actual)
First posted: 11 Feb 2014 (estimated)
Results: Posted 12 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo followed by Placebo	Placebo comparator	Drug: PlaceboSubjects will receive placebo, then one hour later, placebo
Placebo followed by Methamphetamine	Experimental	Drug: Methamphetamine, Drug: PlaceboSubjects will receive placebo, then one hour later, methamphetamine
Entacapone followed by Placebo	Experimental	Drug: Entacapone, Drug: PlaceboSubjects will receive entacapone, then one hour later, placebo
Entacapone followed by Methamphetamine	Experimental	Drug: Entacapone, Drug: MethamphetamineSubjects will receive entacapone, then one hour later, methamphetamine

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (9 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EntacaponeAlso: ComtamEntacapone 200 mg oral dose	Drug	Entacapone followed by Methamphetamine, Entacapone followed by Placebo
MethamphetamineAlso: DesoxynMethamphetamine 20 mg oral dose	Drug	Entacapone followed by Methamphetamine, Placebo followed by Methamphetamine
Placebocapsules compounded to be of similar appearance to the active drugs	Drug	Entacapone followed by Placebo, Placebo followed by Methamphetamine, Placebo followed by Placebo

Primary outcome

Effect of Entacapone on Methamphetamine-induced Mood
Time frame: 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.
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.
Effect of Entacapone on Subjective Effects of Methamphetamine
Time frame: 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.
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) .
Effect of Entacapone on Methamphetamine-induced Stimulation
Time frame: 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.
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.

1 secondary outcome

Cognitive Function
Time frame: 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 and safety

Results posted to the registry on 12 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Subjects	19	18

Primary outcome: Effect of Entacapone on Methamphetamine-induced Mood

Time frame: 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.. Mean (Standard Deviation). Unit: units on a scale

Measure	Baseline n = 12	Placebo Followed by Placebo n = 12	Placebo Followed by Methamphetamine n = 12	Entacapone Followed by Placebo n = 12	Entacapone Followed by Methamphetamine n = 12
Value	12.500 (8.187)	13.750 (9.037)	7.500 (4.166)	9.833 (4.783)	8.750 (4.309)

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

Primary outcome: Effect of Entacapone on Subjective Effects of Methamphetamine

Measure	Baseline n = 12	Placebo Followed by Placebo n = 12	Placebo Followed by Methamphetamine n = 12	Entacapone Followed by Placebo n = 12	Entacapone Followed by Methamphetamine n = 12
Morphine Benzedrine	1.9375 (2.6610)	1.8333 (2.8868)	7.9167 (5.9308)	2.5833 (4.1000)	6.9167 (6.2879)
Lysergic Acid Diethylamide	3.0625 (1.1923)	3.25 (1.1382)	4.75 (2.0944)	3.25 (1.1382)	3.8333 (1.3371)
Pentobarbital Chlorpromazine Alcohol	4.8125 (2.5066)	5.0000 (2.9233)	1.5833 (1.8320)	4.0833 (2.8110)	2.0000 (2.1320)
Benzedrine	4.9583 (1.4869)	5.1667 (2.0817)	8.6667 (3.6013)	5.3333 (2.1462)	7.8333 (3.7376)
Amphetamine	2.0000 (1.8451)	2.1667 (2.4802)	5.9167 (3.4499)	2.5833 (2.6097)	5.5833 (4.0104)

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

Primary outcome: Effect of Entacapone on Methamphetamine-induced Stimulation

Measure	Baseline n = 12	Placebo Followed by Placebo n = 12	Placebo Followed by Methamphetamine n = 12	Entacapone Followed by Placebo n = 12	Entacapone Followed by Methamphetamine n = 12
Value	0.1667 (0.5586)	0.1667 (0.5774)	1.4167 (1.1645)	0.4167 (0.9003)	1.3333 (1.1547)

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

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Open-label Methamphetamine	0 of 19 (0%)	1 of 19 (5.3%)	0 of 19
Placebo-Placebo	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Placebo-Meth	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Entacapone-Placebo	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Entacapone-Meth	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Methamphetamine Dependence

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jonathan C Fellers, MD principal investigator

Oregon Health and Science University

William F Hoffman, MD, PhD principal investigator

VA Portland Healthcare System

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Entacapone and Methamphetamine in people with Methamphetamine Dependence, run by Oregon Health and Science University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Entacapone on Methamphetamine-induced Mood (time frame: 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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02058966.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2019.