A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals

NCT01136356 | Completed Phase 1 Results

• 3 other identifiers: NIDA-08045-9R01DA008045DPMC
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Buprenorphine is an approved medication for the treatment of opioid dependence. It is typically administered once daily as a sublingual tablet combined with naloxone (i.e., Suboxone). Evidence suggests buprenorphine produces relatively low levels of physical dependence. In addition, some research suggests there is relatively little withdrawal following cessation of chronically administered buprenorphine. This study will examine the spontaneous withdrawal associated with abrupt cessation of buprenorphine compared to morphine in opioid dependent individuals. This study will assess the characteristics and time course of withdrawal using subject-rated and observer-rated measures of opioid withdrawal. Physiologic measures and psychomotor performance will be collected during chronic opioid administration and during placebo administration (i.e., during spontaneous withdrawal). Particular attention will be paid to the differences (if any) in sleep disturbances and withdrawal associated hyperalgesia.

Conditions

Opioid Abuse; Opioid Dependence

Keywords

opioid pharmacology; buprenorphine; morphine; withdrawal; human research

Outcome Measures

Primary Outcomes (1)

• Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS)

  Clinical Opiate Withdrawal Scale (COWS) is an observer-rated tool for quantifying opioid withdrawal. The scale ranges from 0 to 48: Scores 5 to 12 are mild, 13 to 24 are moderate, 25 to 36 are moderately severe, and over 36 are severe withdrawal. The scores on this repeated measure were analyzed by a two-factor ANOVA for mean peak daily COWS ratings.

  Average mean peak opioid withdrawal thirty minutes before and after injection assessed up to 59 days

Secondary Outcomes (2)

• Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)

  Average mean daily peak pain ratings assessed from day 0 to day 18 during the 18 day withdrawal period

• Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI)

  Average mean peak sleep assessed once a week for up to 8 weeks

Study Arms (2)

Morphine, then Buprenorphine

EXPERIMENTAL

Healthy, out of treatment opioid-dependent residential volunteers (N=7) were randomized to receive morphine (120 mg/day i.m.) administered in four divided doses each day for 9 days (30 mg of morphine four times per day). Participants then underwent an 18-day period of spontaneous opioid withdrawal, during which four double blind i.m. placebo injections were administered daily. After the period of spontaneous withdrawal, participants received buprenorphine (32 mg/day i.m.) administered in four divided doses each day for 9 days (8 mg of buprenorphine four times per day) followed by a second 18-day period of spontaneous withdrawal identical to the withdrawal period described above.

Drug: buprenorphine; Drug: morphine

Buprenorphine, then Morphine

EXPERIMENTAL

Healthy, out of treatment opioid-dependent residential volunteers (N=7) were randomized to receive buprenorphine (32 mg/day i.m.) administered in four divided doses each day for 9 days (8 mg of buprenorphine four times per day). Participants then underwent an 18-day period of spontaneous withdrawal, during which four double blind i.m. placebo injections were administered daily. After the period of spontaneous withdrawal, participants received morphine (120 mg/day i.m.) administered in four divided doses each day for 9 days (30 mg of morphine four times per day) followed by a second 18-day period of spontaneous withdrawal identical to the withdrawal period described above.

Drug: buprenorphine; Drug: morphine

Interventions

buprenorphine DRUG

parenteral buprenorphine may be administered at multiple times each day

Buprenorphine, then Morphine; Morphine, then Buprenorphine

morphine DRUG

parenteral morphine may be administered multiple times each day

Buprenorphine, then Morphine; Morphine, then Buprenorphine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be adults ranging in age from 21-55 years old.
• Be dependent on opioids.
• Be willing to accept or desiring of opioid detoxification.
• He healthy as determined by medical screen, history, and vitals.
• Be without significant psychiatric illness besides drug dependence.
• Be without chronic pain.
• Fluent in English (speaking, writing, and reading).
• Be willing and able to participate.

You may not qualify if:

• Previous documented allergy to buprenorphine or morphine.
• Are dependent on other drugs besides opioids and tobacco.
• Have current history of significant use of alcohol or sedative/hypnotics.
• Have evidence of significant medical (e.g., insulin dependent diabetes mellitus) or psychiatric (e.g., schizophrenia) illness.
• Are pregnant (female volunteers will receive a pregnancy test before participation in the study and routinely during the study).
• Have an abnormal or prolongation of the corrected QT interval (QTc) on a baseline electrocardiogram (ECG).
• Are seeking treatment for their substance dependence.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Tompkins DA, Smith MT, Mintzer MZ, Campbell CM, Strain EC. A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine. J Pharmacol Exp Ther. 2014 Feb;348(2):217-26. doi: 10.1124/jpet.113.209478. Epub 2013 Nov 13.

  PMID: 24227768 RESULT

Related Links

• A double Blind, within Subjects Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine; Morphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Morphine Derivatives

Results Point of Contact

• Title: Eric C. Strain, MD
• Organization: Johns Hopkins University, School of Medicine

estrain1@jhmi.edu

410-550-1191

Study Officials

• Eric Strain, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2010
• First Posted: June 3, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 3, 2017
• Results First Posted: March 3, 2017

Record last verified: 2017-01

Locations

US (1)