BUP PGx: Study of Medical Treatment for Methamphetamine Addiction

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00833443
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 84
• Location: 1
• Arms: 2
• Duration (Months): 53.9
• Patients Per Site Per Month: 1.6

Study Details

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

• Study Type: Interventional
• 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: Jan 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jul 1, 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 [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 [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 [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Keith Heinzerling, Assistant Clinical Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00833443
• Other Study ID Numbers: KH_K23; P50DA018185; K23DA023558; DPMC
• First Posted: Feb 2, 2009
• Last Update Posted: Feb 26, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Keith Heinzerling, Assistant Clinical Professor, University of California, Los Angeles: Methamphetamine; Addiction; Pharmacogenomics; Amphetamine; Bupropion; Meth; Crank; Crystal
• Additional relevant MeSH terms: Substance-Related Disorders; Amphetamine-Related Disorders; Bupropion

Study Results

Participant Flow

Recruitment Details	Participants were recruited via advertisements and outreach in the Los Angeles area

Arm/Group Title	Bupropion	Sugar Pill
Arm/Group Description	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. 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.	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.
Period Title: Overall Study
STARTED	41	43
COMPLETED	21	15
NOT COMPLETED	20	28

Baseline Characteristics

Arm/Group Title	Bupropion	Sugar Pill	Total
Arm/Group Description	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. 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.	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.	Total of all reporting groups
Overall Participants	41	43	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (10.1)	38.1 (10.3)	38.4 (10.1)
Sex: Female, Male (Count of Participants)
Female	7 17.1%	9 20.9%	16 19%
Male	34 82.9%	34 79.1%	68 81%
Race/Ethnicity, Customized (participants) [Number]
Hispanic	18 43.9%	17 39.5%	35 41.7%
White	15 36.6%	13 30.2%	28 33.3%
African American	7 17.1%	10 23.3%	17 20.2%
Asian/Pacific Islander	1 2.4%	3 7%	4 4.8%
Region of Enrollment (participants) [Number]
United States	41 100%	43 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Treatment Effectiveness Score
Description	The mean number of methamphetamine-free urine drug screens provided by participants in each group (range 0-36)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion	Sugar Pill
Arm/Group Description	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. 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.	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.
Measure Participants	41	43
Mean (Standard Deviation) [urine drug screens]	16.1 (12.7)	10.6 (11.2)

2. Primary Outcome

Title	End of Treatment Methamphetamine Abstinence
Description	Methamphetamine abstinence confirmed via urine drug screens during the final two weeks of treatment (weeks 11 and 12)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion	Sugar Pill
Arm/Group Description	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. 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.	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.
Measure Participants	41	43
Number [participants]	12 29.3%	6 14%

3. Secondary Outcome

Title	Treatment Retention
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion	Sugar Pill
Arm/Group Description	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. 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.	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.
Measure Participants	41	43
Mean (Standard Deviation) [days]	61.0 (28.8)	49.5 (31.7)

4. Post-Hoc Outcome

Title	End of Treatment Methamphetamine Abstinence
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication Adherent	NOT Medication Adherent
Arm/Group Description	Participants in the bupropion group with a week 6 bupropion/hydroxybupropion plasma levels suggesting medication adherence	Participants in the bupropion group with a week 6 bupropion/hydroxybupropion plasma levels suggesting medication NON-adherence
Measure Participants	13	28
Number [participants]	7 17.1%	5 11.6%

Adverse Events

Arm/Group Title	Bupropion		Sugar Pill
Arm/Group Description	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. 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.		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.
All Cause Mortality
	Bupropion		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupropion		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/41 (4.9%)		2/43 (4.7%)
Cardiac disorders
Chest pain	1/41 (2.4%)	1	0/43 (0%)	0
Infections and infestations
Liver abscess	0/41 (0%)	0	1/43 (2.3%)	1
Psychiatric disorders
Suicidal ideation	1/41 (2.4%)	1	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Bupropion		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/41 (70.7%)		17/43 (39.5%)
Cardiac disorders
Elevated blood pressure	2/41 (4.9%)		0/43 (0%)
Gastrointestinal disorders
Diarrhea	4/41 (9.8%)		0/43 (0%)
Dry mouth	3/41 (7.3%)		2/43 (4.7%)
Nausea/vomiting	3/41 (7.3%)		1/43 (2.3%)
Nervous system disorders
Headache	5/41 (12.2%)		1/43 (2.3%)
Dizziness	2/41 (4.9%)		1/43 (2.3%)
Muscle twitching	2/41 (4.9%)		0/43 (0%)
Psychiatric disorders
Insomnia	9/41 (22%)		6/43 (14%)
"Amped up"	6/41 (14.6%)		2/43 (4.7%)
Depressed mood	5/41 (12.2%)		3/43 (7%)
Panic attack	2/41 (4.9%)		1/43 (2.3%)
Paranoia	2/41 (4.9%)		0/43 (0%)
Vivid dreams/nightmares	2/41 (4.9%)		0/43 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.