Medications Development for Drug Abuse Disorders

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.

Study Overview

• Status: Completed
• Conditions: Opioid Dependence; Opioid Related Disorders; Opioid Addiction
• Intervention / Treatment: Drug: Buprenorphine/naloxone; Drug: Clonidine; Drug: Tramadol ER

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University (BPRU) Bayview Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Eric C. Strain, M.D., Johns Hopkins University

Publications and helpful links

General Publications

• Dunn KE, Tompkins DA, Bigelow GE, Strain EC. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):885-893. doi: 10.1001/jamapsychiatry.2017.1838. Erratum In: JAMA Psychiatry. 2017 Sep 1;74(9):975. JAMA Psychiatry. 2018 Apr 1;75(4):409.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Actual): July 6, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Sympatholytics; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination; Tramadol; Clonidine
• Other Study ID Numbers: NIDA-018125; DPMC (Other Identifier: NIDA); R01DA018125 (U.S. NIH Grant/Contract); NA_00037871 (Other Identifier: JHUSOM IRB)