A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals

Study Overview
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Brief Summary
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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.

Official Title
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A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals

Conditions
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Opioid Abuse, Opioid Dependence

Intervention / Treatment
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* Drug: buprenorphine
* Drug: morphine


Participation Criteria
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Eligibility Criteria
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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.

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morphine, then Buprenorphine<br>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<br>* parenteral buprenorphine may be administered at multiple times each day<br>Drug: morphine<br>* parenteral morphine may be administered multiple times each day<br>|
| Experimental: Buprenorphine, then Morphine<br>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<br>* parenteral buprenorphine may be administered at multiple times each day<br>Drug: morphine<br>* parenteral morphine may be administered multiple times each day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Visual Analog Scale (VAS) measures subjective ratings on pain. The scale on this measurement ranges from 0 being None to 100 being Extremely. The results below reflect the subjective measurements of pain taken from day 0 to day 18 of withdrawal from both morphine and buprenorphine. | 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) | Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality, total scores range from 0 (better) to 21(worse). The data that has been reported reflects the peak scores on the PSQI during the withdrawal period from both morphine and buprenorphine. | Average mean peak sleep assessed once a week for up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid pharmacology, buprenorphine, morphine, withdrawal, human research