A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals

Johns Hopkins University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Opioid Abuse; Opioid Dependence

Treatments: Drug: buprenorphine; Drug: morphine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01136356

NIDA-08045-9

R01DA008045 (U.S. NIH Grant/Contract)

DPMC

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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12 participants in 2 patient groups

Morphine, then Buprenorphine

Experimental group

Description:

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.

Treatment:

Drug: morphine

Drug: buprenorphine

Buprenorphine, then Morphine

Experimental group

Description:

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.

Treatment:

Drug: morphine

Drug: buprenorphine