Amphetamine Dependence, Methamphetamine, Methamphetamine Dependence, Pharmacogenetics, Substance Abuse
Conditions
Keywords
Methamphetamine, Addiction, Pharmacogenomics, Amphetamine, Bupropion, Meth, Crank, Crystal
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.
Interventions
DRUGBupropion
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.
Sponsors
National Institute on Drug Abuse (NIDA)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Effectiveness Score | 12 weeks | The mean number of methamphetamine-free urine drug screens provided by participants in each group (range 0-36) |
| 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
| Measure | Time frame |
|---|---|
| Treatment Retention | 12 weeks |
Countries
United States
Participant flow
Recruitment details
Participants were recruited via advertisements and outreach in the Los Angeles area
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 41 |
| Sugar Pill 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. | 43 |
| Total | 84 |
Baseline characteristics
| Characteristic | Bupropion | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 10.1 | 38.1 years STANDARD_DEVIATION 10.3 | 38.4 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized African American | 7 participants | 10 participants | 17 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 18 participants | 17 participants | 35 participants |
| Race/Ethnicity, Customized White | 15 participants | 13 participants | 28 participants |
| Region of Enrollment United States | 41 participants | 43 participants | 84 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 34 Participants | 34 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 41 | 17 / 43 |
| serious Total, serious adverse events | 2 / 41 | 2 / 43 |
Outcome results
Primary
End of Treatment Methamphetamine Abstinence
Methamphetamine abstinence confirmed via urine drug screens during the final two weeks of treatment (weeks 11 and 12)
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bupropion | End of Treatment Methamphetamine Abstinence | 12 participants |
| Sugar Pill | End of Treatment Methamphetamine Abstinence | 6 participants |
Primary
Treatment Effectiveness Score
The mean number of methamphetamine-free urine drug screens provided by participants in each group (range 0-36)
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion | Treatment Effectiveness Score | 16.1 urine drug screens | Standard Deviation 12.7 |
| Sugar Pill | Treatment Effectiveness Score | 10.6 urine drug screens | Standard Deviation 11.2 |
Secondary
Treatment Retention
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion | Treatment Retention | 61.0 days | Standard Deviation 28.8 |
| Sugar Pill | Treatment Retention | 49.5 days | Standard Deviation 31.7 |
Post Hoc
End of Treatment Methamphetamine Abstinence
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bupropion | End of Treatment Methamphetamine Abstinence | 7 participants |
| Sugar Pill | End of Treatment Methamphetamine Abstinence | 5 participants |