A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Johns Hopkins University
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Morphine, then Buprenorphine
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.
Intervention: buprenorphine (Drug)
Morphine, then Buprenorphine
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.
Intervention: morphine (Drug)
Buprenorphine, then Morphine
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.
Intervention: buprenorphine (Drug)
Buprenorphine, then Morphine
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.
Intervention: morphine (Drug)
Outcomes
Primary Outcomes
Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS)
Time Frame: Average mean peak opioid withdrawal thirty minutes before and after injection assessed up to 59 days
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.
Secondary Outcomes
- 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)