Cocaine Dependence, Opiate Dependence
Conditions
Keywords
addiction, cocaine, methadone, opiates, atomoxetine
Brief summary
The main goal of this study is to evaluate the safety and tolerability of 40 or 80 mg atomoxetine as a treatment for cocaine dependence. The Phase I studies summarized above support the safety of atomoxetine in combination with stimulants. As the next step, the investigators will evaluate the safety and tolerability of atomoxetine in a small clinical trial with cocaine users. If atomoxetine is found to be promising in this study and sufficiently powered, double-blind, placebo-controlled studies will be proposed.
Detailed description
This will be an approximately 13 to 14 week double-blind, placebo-controlled clinical trial testing the safety and feasibility of atomoxetine (40 or 80 mg/day) treatment, compared to placebo, in methadone-stabilized stimulant users. The study will have 3 phases: 1) a one to two week- methadone-induction phase; 2) an 8-week treatment phase; and 3) 1 week atomoxetine taper and about a 4-week methadone taper and detoxification or transfer phase. Subjects will be randomized to three treatment arms: 40 mg (n=15) atomoxetine, or 80 mg (n=15) atomoxetine, or placebo (n=15). During the methadone induction phase, subjects will be stabilized on methadone. During induction onto methadone, participants will be administered increasing doses of methadone starting at 30 mg daily, and this dose will be increased for stabilization of opiate withdrawal symptoms from 40 mg up to 140 mg depending on individual need. Based on the clinic schedule between 1 to 2 weeks after methadone treatment is initiated , atomoxetine treatment will be started at 40 mg/day. For those assigned to 80 mg of atomoxetine, the dose will be titrated up to 80 mg/day on the second week of treatment phase. At the end of the treatment-phase, subjects will undergo detoxification from methadone over a 4-week period based on an individual's needs, and they will concurrently be tapered off atomoxetine. All participants will receive a weekly one-hour of individual psychotherapy (Cognitive Behavioral Therapy) with experienced clinicians specifically trained to deliver the therapy, and who will receive ongoing supervision. This study has been terminated as of march 2014 due to the lack of funding, only 14 were enrolled with 11 subject completers. (June 2016)
Interventions
DRUGAtomoxetine, low dose
The effects of 40mg low dose atomoxetine will be compared to placebo and to the 80mg atomoxetine high dose.
DRUGAtomoxetine, high dose
The effects of 80mg of high dose atomoxetine will be compared to placebo and to 40mg atomoxetine low dose.
DRUGPlacebo
The effects of placebo will be compared to the parallel groups of Atomoxetine high (80mg) dose and Atomoxetine low (40mg) dose.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* • Men and women between 18 and 65 years old. * Current opioid dependence as evidenced by 1) documentation of prior treatment for opioid dependence or signs of withdrawal, 2) self-reported history of opioid dependence for 12 consecutive months and, 3) a positive urine toxicology screen for opiates. * Diagnosis of opioid dependence and cocaine dependence by Diagnostic and Statisical Manual (DSM-IV) -criteria as well as laboratory confirmation of recent cocaine use in the form of positive urine toxicology during the month prior to study entry. * For those who recently participated in a research study, at least 2 weeks of washout period before enrollment. * A history of cocaine use,( a minimum of 1/2 gram during the preceding 30 days). * Must be seeking treatment for opioid and cocaine use. * For women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests.
Exclusion criteria
* • Serious medical illnesses including hypertension, tachycardia, bradycardia, or other arrhythmias and major cardiovascular, cerebrovascular, renal, endocrine, or hepatic disorders; * Serious psychiatric illness, history of psychosis, schizophrenia or bipolar type I disorder. * Current major depression. Subjects with current depressive symptoms not meeting criteria will be included in the study, with the exception of those endorsing suicidal and homicidal thoughts, will be excluded even if full criteria for major depression are not met. * Current diagnosis of alcohol or drug dependence other than opiates, cocaine, nicotine and cannabis. * Current use of over-the-counter or prescription psychoactive drugs (antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants) or drugs that would be expected to have major interactions with drugs to be tested, e.g., benzodiazepines, codeine, percocet, and other opiate drugs that will interact with methadone. * Has not been treated with monoamine oxidase inhibitors within the last fourteen days. * Liver function tests (ALT or AST) greater than 3 times normal. * Known allergy or intolerance to atomoxetine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Retention | 8 weeks of treatment | The number of participants completing all 8 weeks of treatment phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale | 8 weeks of treatment | Center for Epidemiological Studies-Depression. The CES-D is a 20-item self-report measure of depressive symptoms. Each of the 20 items can yield a score from 0 to 3 for a maximum total CES-D score of 60. Larger values represent more severe symptoms. It is a validated instrument with a score of 16 or more indicating clinically significant depression. The CES-D change score was computed as (total baseline CES-D score - total CES-D score at end of study). |
Countries
United States
Participant flow
Recruitment details
Adult male and female participants were recruited from the Greater New Haven area from September 2012 to January 2014 by word-of-mouth, flyers and from referrals from treatment centers in the local area. The study was conducted in an outpatient clinic of the West Haven VA Hospital.
Pre-assignment details
After eligibility was determined, participants were randomized to placebo, 40 mg atomoxetine or 80 mg atomoxetine. The study consisted of 3 phases 1) a two-week methadone induction phase 2) an 8-week treatment phase and 3) a 4-week taper and detoxification or transfer phase.
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine, Low Dose 1 capsule containing 40mg of atomoxetine by mouth everyday for 8 weeks followed by 1 week of daily placebo capsules.
Atomoxetine, low dose: The effects of 40mg low dose atomoxetine will be compared to placebo and to the 80mg atomoxetine high dose. | 5 |
| Atomoxetine, High Dose One capsule containing 80mg of atomoxetine by mouth everyday for 8 weeks, followed by 1 week of daily 40mg atomoxetine capsules
Atomoxetine, high dose: The effects of 80mg of high dose atomoxetine will be compared to placebo and to 40mg atomoxetine low dose. | 5 |
| Placebo (Sugar Pill) 1 placebo capsule by mouth everyday for 8 weeks of treatment invention followed by one week of placebo capsule during study medication taper.
Placebo: The effects of placebo will be compared to the parallel groups of Atomoxetine high (80mg) dose and Atomoxetine low (40mg) dose. | 4 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | Total |
|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 8 | 47.6 years STANDARD_DEVIATION 5.63 | 43.6 years STANDARD_DEVIATION 0.95 | 42.3 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 5 participants | 5 participants | 4 participants | 14 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 5 | 4 / 5 | 1 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 4 |
Outcome results
Primary
Treatment Retention
The number of participants completing all 8 weeks of treatment phase.
Time frame: 8 weeks of treatment
Population: Descriptive statistics were calculated for all enrolled subjects. A full statistical analysis was not performed due to study termination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atomoxetine, Low Dose | Treatment Retention | 2 participants |
| Atomoxetine, High Dose | Treatment Retention | 5 participants |
| Placebo (Sugar Pill) | Treatment Retention | 4 participants |
Secondary
Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale
Center for Epidemiological Studies-Depression. The CES-D is a 20-item self-report measure of depressive symptoms. Each of the 20 items can yield a score from 0 to 3 for a maximum total CES-D score of 60. Larger values represent more severe symptoms. It is a validated instrument with a score of 16 or more indicating clinically significant depression. The CES-D change score was computed as (total baseline CES-D score - total CES-D score at end of study).
Time frame: 8 weeks of treatment
Population: Descriptive statistics were calculated for all enrolled subjects. A full statistical analysis was not performed due to study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine, Low Dose | Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale | -2.2 units on a scale | Standard Deviation 5.2 |
| Atomoxetine, High Dose | Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale | -2.2 units on a scale | Standard Deviation 9.1 |
| Placebo (Sugar Pill) | Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale | -3.3 units on a scale | Standard Deviation 11.2 |