Methamphetamine Dependence
Conditions
Keywords
methamphetamine, addiction, relapse, atomoxetine
Brief summary
The purpose of this study is to examine the ability of atomoxetine compared to placebo to increase time to relapse in methamphetamine dependent volunteers. Our hypothesis is that atomoxetine will increase time before (if) the participant relapses.
Detailed description
During the study participants will spend the initial 2-weeks of the study at an inpatient facility. This will help participants initiate withdrawal. During the following 8-weeks the participant will come in for 3-4 visits each week. Three of these visits will be with the research assistants and one visit will be with a therapist in order to work with the participant using a cognitive behavioral therapy approach. Therapy visits are typically scheduled on a day that the participant is coming for clinic anyways so the number of visits per week is typically 3. During the 10-week period the investigators will collect various measures, including vitals, cognitive assessments, mood assessments, urine drug screens, weekly use reports of methamphetamine, and any reports of symptoms or side effects. This will tell the investigators if atomoxetine is safe and if a participant lapsed or relapsed.
Interventions
DRUGAtomoxetine
During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7)
DRUGplacebo
participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Arkansas
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 65 Years
Healthy volunteers
No
Inclusion criteria
. * 18-65 years old * Seeking treatment for METH use * METH dependence, as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV. * At least weekly self-reported METH use during a preceding three month period * Women of childbearing age must have a negative pregnancy test, agree to adequate contraception to prevent pregnancy during the study, agree to monthly pregnancy testing, and not be nursing * Men must agree to use effective means of contraception during the study.
Exclusion criteria
. * Suicide attempts within the past 12 months or either suicidal ideations or psychotic symptoms in the past 6 months as determined by a study physician. * Current opioid, alcohol or sedative physical dependence or cocaine dependence * Major cardiovascular disorder that contraindicates study participation (e.g., history of myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia, hypertension \[i.e., \> 160 SBP or \> 100 DBP\] or an unstable medical condition (e.g., untreated bacterial infection) as determined by the study physician. * Schizophrenia or bipolar disorder of any type * Present or recent use (within 2 weeks) of over-the-counter or prescription drug that would be expected to have major interaction with atomoxetine (e.g., an monoamine oxidase inhibitor (MAOI), paroxetine, fluoxetine, quinidine, dopamine, albuterol, or other β2-agonists) * Medical contraindication to receiving atomoxetine (e.g., severe hepatic impairment, glaucoma, heart disease, hypertension, seizure disorders, documented hypersensitivity to atomoxetine); or other bronchospastic condition, (2nd or 3rd degree AV block, sick sinus rhythm, severe hepatic impairment, documented hypersensitivity to atomoxetine) * Liver function tests (i.e., liver enzymes) greater than two times normal levels * Systolic blood pressure of \< 90 or \> 160 mmHg, diastolic blood pressure of \< 60 or \> 100 mmHg, or sitting heart rate of \< 55 or \> 100 beats/min or blood pressure readings \> 140 systolic or \> 90 diastolic on three separate, consecutive occasions. * History of pheochromocytoma * Pregnant or nursing female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Till Relapse | 57 days | The number of days until a participant has a relapse, which will be measured by qualitative urine drug screens. To ensure a large enough sample, those who drop out prior to completing the residential stay will be included in this analysis (with minus days until relapse) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Group receiving atomoxetine
Atomoxetine: During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7) | 6 |
| Placebo Group will receive placebo instead of atomoxetine
placebo: participants in this group will receive 1 dose of placebo daily for the entire 10-weeks. | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | high blood pressure | 0 | 1 |
| Overall Study | noncompliance with rules of residential | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | Atomoxetine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 3 Participants | 5 Participants | 2 Participants |
| Gender Male | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment United States | 7 participants | 13 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 2 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
Time Till Relapse
The number of days until a participant has a relapse, which will be measured by qualitative urine drug screens. To ensure a large enough sample, those who drop out prior to completing the residential stay will be included in this analysis (with minus days until relapse)
Time frame: 57 days
Population: Only 4 of 13 finished the 2-week residential stay. Since subjects who drop out are deemed relapsed, all subjects receiving \>/=1 dose of study med were included in the analyses. Those who dropped out before completing the residential stay were considered relapsed by the second day and the date of discharge was subtracted from this relapse date.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atomoxetine | Time Till Relapse | 7 Days to Relapse |
| Placebo | Time Till Relapse | -8 Days to Relapse |
Comparison: Due to skewed data, Kruskal Wallis Test was used.p-value: <0.05Kruskal-Wallis