Study of Medical Treatment for Methamphetamine Addiction (BUP PGx)

• Sponsor: University of California, Los Angeles
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Keith Heinzerling, University of California, Los Angeles

Study Description

Brief Summary:

Currently there are no medications approved for the treatment of methamphetamine addiction. Bupropion is an antidepressant that is approved by the Food and Drug Administration (FDA) for the treatment of depression and for cigarette smoking cessation but is not approved by the FDA for the treatment of methamphetamine addiction. Preliminary research studies suggest that bupropion may help people receiving treatment for methamphetamine addiction to reduce or to stop their methamphetamine use. But results of these studies also suggest that bupropion may help certain groups of patients more than others, such as men versus women and light versus heavy methamphetamine users, although the reasons for this difference are not known. One possibility is that a person's genetic make up may influence whether or not they respond to treatment with bupropion for methamphetamine addiction.

The purpose of the study is to determine if bupropion is can help people reduce or stop their methamphetamine use and to investigate whether genetic variations influence whether people respond to treatment with bupropion for methamphetamine addiction, which may help doctors and patients better decide if treatment with bupropion will be beneficial or not. To identify possible genetic variations that influence response to bupropion, we will perform genetic tests on blood or saliva specimens from participants receiving treatment with either bupropion or placebo (which is a pill that contains no medication) in conjunction with standard cognitive behavioral therapy drug counseling. We will compare methamphetamine use, as assessed with urine drug screens, among participants receiving bupropion versus those receiving placebo to determine if bupropion helps people to reduce or stop their methamphetamine use. We will then compare the results of the genetic tests among participants who respond and who do not respond to bupropion. In addition, since the amount of methamphetamine a person uses was associated with response to bupropion in preliminary studies, we will also compare the results of genetic testing among persons with heavy versus light methamphetamine use before entering treatment.

Results of this study have the potential to provide insights into the biology of methamphetamine addiction and help increase the understanding of how bupropion works. This information could be useful to develop effective medications for methamphetamine addiction and to improve the ability of clinicians to provide treatment to patients with methamphetamine addiction.

Condition or disease	Intervention/treatment	Phase
Methamphetamine; Amphetamine Dependence; Pharmacogenetics; Methamphetamine Dependence; Substance Abuse	Drug: Bupropion	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	84 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Pharmacogenomics and Medication Development for Methamphetamine Dependence
Study Start Date :	January 2009
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	July 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bupropion; Bupropion dose will start at 150 mg per day (one 150 mg sustained release tablet per day) for days 1-3 of the first week. The dose will then be increased to 300 mg per day (one 150 mg sustained release tablet twice daily) on day 4 and will remain 300 mg per day until the last week of the medication phase, when the dose will be decreased to 150 mg per day (one 150 mg sustained release tablet per day) for the last three days.	Drug: Bupropion; Bupropion dose will start at 150 mg per day (one 150 mg sustained release tablet per day) for days 1-3 of the first week. The dose will then be increased to 300 mg per day (one 150 mg sustained release tablet twice daily) on day 4 and will remain 300 mg per day until the last week of the medication phase, when the dose will be decreased to 150 mg per day (one 150 mg sustained release tablet per day) for the last three days. The medication treatment phase is for 12 weeks.; Other Names: Zyban; Wellbutrin
Placebo Comparator: Sugar Pill	Drug: Bupropion; Bupropion dose will start at 150 mg per day (one 150 mg sustained release tablet per day) for days 1-3 of the first week. The dose will then be increased to 300 mg per day (one 150 mg sustained release tablet twice daily) on day 4 and will remain 300 mg per day until the last week of the medication phase, when the dose will be decreased to 150 mg per day (one 150 mg sustained release tablet per day) for the last three days. The medication treatment phase is for 12 weeks.; Other Names: Zyban; Wellbutrin

Outcome Measures

Primary Outcome Measures :

1. Treatment Effectiveness Score [ Time Frame: 12 weeks ]
   The mean number of methamphetamine-free urine drug screens provided by participants in each group (range 0-36)
2. End of Treatment Methamphetamine Abstinence [ Time Frame: 12 weeks ]
   Methamphetamine abstinence confirmed via urine drug screens during the final two weeks of treatment (weeks 11 and 12)

Secondary Outcome Measures :

1. Treatment Retention [ Time Frame: 12 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. 18 years of age or older;
2. meet DSM-IV criteria for methamphetamine dependence;
3. seeking treatment for MA problems;
4. specific range of methamphetamine use in the 30 days prior to study entry;
5. willing and able to comply with study procedures, including genotyping;
6. willing and able to provide written informed consent;
7. if female, not pregnant or lactating and willing to use an acceptable method of barrier birth control (e.g. condoms) during the trial.

Exclusion Criteria:

1. have a medical condition that, in the study physician's judgment, may interfere with safe study participation (e.g., active TB, unstable cardiac, renal, or liver disease, unstable diabetes);
2. have a current neurological disorder (e.g., organic brain disease, dementia) or major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar disorder) as assessed by the SCID or a medical history which would make study agent compliance difficult or which would compromise informed consent, or recent (past 30 days) history of suicide attempts and/or current serious suicidal intention or plan as assessed by the SCID;
3. currently on prescription medication that is contraindicated for use with bupropion;
4. have current dependence on cocaine, opiates, alcohol, or benzodiazepines as defined by DSM-IV-TR;
5. have a history of alcohol dependence within the past three years;
6. have a history of a seizure disorder;
7. have a medical condition (such as serious head injury) that is associated with increased risk of seizures or on a medication that lowers the seizure threshold;
8. have a history of anorexia or bulimia;
9. have current hypertension uncontrolled by medication, or any other circumstances that, in the opinion of the investigators, would compromise participant safety;
10. have a history of sensitivity to bupropion.

Contacts and Locations

Locations

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United States, California
UCLA Clinical Research Site 910 Vine St
Los Angeles, California, United States, 90038

Sponsors and Collaborators

University of California, Los Angeles

National Institute on Drug Abuse (NIDA)

Investigators

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Principal Investigator:	Keith G Heinzerling, MD MPH	UCLA Dept of Family Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Heinzerling KG, Swanson AN, Hall TM, Yi Y, Wu Y, Shoptaw SJ. Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use. Addiction. 2014 Nov;109(11):1878-86. doi: 10.1111/add.12636. Epub 2014 Aug 5.

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Responsible Party:	Keith Heinzerling, Assistant Clinical Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00833443 History of Changes
Other Study ID Numbers:	KH_K23; P50DA018185 ( U.S. NIH Grant/Contract ); K23DA023558 ( U.S. NIH Grant/Contract ); DPMC ( Other Identifier: NIH / NIDA )
First Posted:	February 2, 2009
Results First Posted:	February 26, 2014
Last Update Posted:	February 26, 2014
Last Verified:	January 2014

Keywords provided by Keith Heinzerling, University of California, Los Angeles:

Methamphetamine; Addiction; Pharmacogenomics; Amphetamine	Bupropion; Meth; Crank; Crystal

Additional relevant MeSH terms:

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Substance-Related Disorders; Amphetamine-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bupropion; Methamphetamine; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action	Dopamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agents; Adrenergic Uptake Inhibitors