A Drug Treatment for Cocaine Users Who Are Also on Methadone Maintenance Treatment
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Atomoxetine, low dose 1 capsule containing 40mg of atomoxetine by mouth everyday for 8 weeks followed by 1 week of daily placebo capsules. |
Drug: Atomoxetine, low dose
The effects of 40mg low dose atomoxetine will be compared to placebo and to the 80mg atomoxetine high dose.
Other Names:
|
| Active Comparator: Atomoxetine, high dose One capsule containing 80mg of atomoxetine by mouth everyday for 8 weeks, followed by 1 week of daily 40mg atomoxetine capsules |
Drug: Atomoxetine, high dose
The effects of 80mg of high dose atomoxetine will be compared to placebo and to 40mg atomoxetine low dose.
Other Names:
|
| Placebo Comparator: 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. |
Drug: Placebo
The effects of placebo will be compared to the parallel groups of Atomoxetine high (80mg) dose and Atomoxetine low (40mg) dose.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Treatment Retention [8 weeks of treatment]
The number of participants completing all 8 weeks of treatment phase.
Secondary Outcome Measures
- 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).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Veterans Affairs Hospital | West Haven | Connecticut | United States | 06516 |
Sponsors and Collaborators
- Yale University
Investigators
- Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D., Yale University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1206010407
Study Results
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 Detail | 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. |
| Arm/Group Title | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: Overall Study | |||
| STARTED | 5 | 5 | 4 |
| COMPLETED | 2 | 5 | 4 |
| NOT COMPLETED | 3 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 5 | 5 | 4 | 14 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
36.2
(8.0)
|
47.6
(5.63)
|
43.6
(0.95)
|
42.3
(7.4)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
80%
|
2
40%
|
1
25%
|
7
50%
|
| Male |
1
20%
|
3
60%
|
3
75%
|
7
50%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
5
100%
|
5
100%
|
4
100%
|
14
100%
|
Outcome Measures
| Title | Treatment Retention |
|---|---|
| Description | The number of participants completing all 8 weeks of treatment phase. |
| Time Frame | 8 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Descriptive statistics were calculated for all enrolled subjects. A full statistical analysis was not performed due to study termination. |
| Arm/Group Title | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 5 | 5 | 4 |
| Number [participants] |
2
40%
|
5
100%
|
4
100%
|
| Title | Change Score in the Center for Epidemiological Studies-Depression (CES-D) Scale |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Descriptive statistics were calculated for all enrolled subjects. A full statistical analysis was not performed due to study termination. |
| Arm/Group Title | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 2 | 5 | 4 |
| Mean (Standard Deviation) [units on a scale] |
-2.2
(5.2)
|
-2.2
(9.1)
|
-3.3
(11.2)
|
Adverse Events
| Time Frame | Adverse events were collected once per week on all enrolled subjects for the 8 weeks of the treatment phase. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The assessment of adverse events utilized the Brief Symptom Inventory (BSI), an instrument that consists of 77 items. | |||||
| Arm/Group Title | Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/5 (0%) | 0/4 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Atomoxetine, Low Dose | Atomoxetine, High Dose | Placebo (Sugar Pill) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/5 (40%) | 4/5 (80%) | 1/4 (25%) | |||
| Gastrointestinal disorders | ||||||
| heartburn | 0/5 (0%) | 0 | 1/5 (20%) | 8 | 0/4 (0%) | 0 |
| constipation | 1/5 (20%) | 3 | 2/5 (40%) | 4 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||
| insomnia | 1/5 (20%) | 3 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| dry mouth | 1/5 (20%) | 4 | 2/5 (40%) | 10 | 0/4 (0%) | 0 |
| headache | 0/5 (0%) | 0 | 1/5 (20%) | 8 | 1/4 (25%) | 1 |
| dizziness | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| chills | 0/5 (0%) | 0 | 1/5 (20%) | 3 | 0/4 (0%) | 0 |
| yawning | 0/5 (0%) | 0 | 1/5 (20%) | 8 | 0/4 (0%) | 0 |
| agitation | 1/5 (20%) | 3 | 3/5 (60%) | 6 | 0/4 (0%) | 0 |
| depression | 0/5 (0%) | 0 | 3/5 (60%) | 9 | 1/4 (25%) | 5 |
| tiredness | 0/5 (0%) | 0 | 3/5 (60%) | 6 | 1/4 (25%) | 4 |
| anxiety | 1/5 (20%) | 1 | 2/5 (40%) | 5 | 0/4 (0%) | 0 |
| decreased libido | 0/5 (0%) | 0 | 1/5 (20%) | 8 | 0/4 (0%) | 0 |
| increased perspiration | 0/5 (0%) | 0 | 2/5 (40%) | 3 | 0/4 (0%) | 0 |
| decreased appetite | 1/5 (20%) | 1 | 1/5 (20%) | 3 | 0/4 (0%) | 0 |
| nightmares | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/4 (25%) | 2 |
| numbness | 1/5 (20%) | 2 | 2/5 (40%) | 2 | 0/4 (0%) | 0 |
| decreased concentration | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/4 (25%) | 2 |
| drowsiness | 0/5 (0%) | 0 | 2/5 (40%) | 10 | 1/4 (25%) | 2 |
| hallucinations | 1/5 (20%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| tingling | 0/5 (0%) | 0 | 1/5 (20%) | 3 | 0/4 (0%) | 0 |
| ataxia | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| cramps | 1/5 (20%) | 8 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| shortness of breath | 0/5 (0%) | 0 | 2/5 (40%) | 7 | 0/4 (0%) | 0 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. Mehmet Sofuoglu, Principal Investigator |
|---|---|
| Organization | Yale University |
| Phone | 203 937-4809 |
| mehmet.sofuoglu@yale.edu |
- 1206010407