Medications Development for Drug Abuse Disorders

Study Overview
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Brief Summary
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This is a study of tramadol as an agent for short-term opioid withdrawal treatment. A randomized, double blind clinical trial comparing the efficacy and safety of tramadol to clonidine and buprenorphine in the short-term treatment of opioid withdrawal will be conducted. Opioid dependent participants will be treated on a residential unit. The primary outcome measure is opioid withdrawal symptoms.

Official Title
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Medications Development for Drug Abuse Disorders

Conditions
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Opioid Related Disorders, Opioid Dependence, Opioid Addiction

Intervention / Treatment
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* Drug: Buprenorphine/naloxone
* Drug: Clonidine
* Drug: Tramadol ER


Participation Criteria
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Eligibility Criteria
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Inclusion/Exclusion Criteria: Participants in this study will be males and females between the ages of 18 and 60 years. Applicants must be opioid dependent based upon the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID); in addition, they must have an opioid positive urine during the screening process (or have evidence of opioid withdrawal). They must be healthy, with no significant medical illnesses (e.g., insulin dependent diabetes), and without significant psychiatric illness (e.g., schizophrenia) besides their drug dependence. Females will have a pregnancy test prior to study enrollment, and if found to be pregnant will be excluded and referred to a substance abuse program for pregnant women (the Center for Addiction and Pregnancy) on the campus. Volunteers will also be excluded if they have pre-admission hypotension (due to the use of clonidine in the study). Applicants with a history of seizures (including substance-related seizures, such as alcohol withdrawal related) will be excluded. Alcohol and/or sedative dependence will be specific exclusionary criteria (given the small risk of seizures associated with tramadol use). Allergies to any of the study medications will be grounds for exclusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: buprenorphine<br>Sublingual buprenorphine/naloxone tablets (or placebo) | Drug: Buprenorphine/naloxone<br>* up to 8/2 mg Sublingual (SL) per day<br>* Other names: Suboxone;|
| Active Comparator: clonidine<br>Oral clonidine tablets (or placebo) | Drug: Clonidine<br>* up to 0.8 mg per day (oral)<br>* Other names: Catapres;|
| Experimental: tramadol ER<br>Oral tramadol tablets (or placebo) | Drug: Tramadol ER<br>* up to 600 mg per day<br>* Other names: Ultram;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period. | Outcomes represent mean peak withdrawal as rated on the Clinical Opiate Withdrawal Scale (COWS) total score. Withdrawal was collected 7 times daily and daily peak values were identified for each participant and averaged together as a function of group. Primary outcomes were mean peak results from the 7-day taper period and first 7 days post-taper. The COWS is an 11-item observer-rated measure of opioid withdrawal severity. Items are rated on individual Likert scales and the total score range is 0-47. Higher values indicate more severe withdrawal. | 14 days total |