Opioid Abuse, Opioid Dependence
Conditions
Keywords
opioid pharmacology, buprenorphine, morphine, withdrawal, human research
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.
Interventions
DRUGbuprenorphine
parenteral buprenorphine may be administered at multiple times each day
DRUGmorphine
parenteral morphine may be administered multiple times each day
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI) | Average mean peak sleep assessed once a week for up to 8 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
The study site was an in-patient research-based clinic affiliated with the Johns Hopkins University School of Medicine.
Participants by arm
| Arm | Count |
|---|---|
| Within Subjects Design Participants received both study drugs (buprenorphine and morphine) in a randomized sequence. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 18-day Withdrawal | Physician Decision | 1 | 0 |
| First 18-day Withdrawal | Withdrawal by Subject | 3 | 0 |
| Second 18-day Withdrawal | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Within Subjects Design |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gender Female | 0 Participants |
| Gender Male | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 12 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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.
Time frame: Average mean peak opioid withdrawal thirty minutes before and after injection assessed up to 59 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Morphine | Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS) | 12.6 units on a scale |
| Buprenorphine | Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS) | 1.3 units on a scale |
Secondary
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.
Time frame: Average mean daily peak pain ratings assessed from day 0 to day 18 during the 18 day withdrawal period
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 13 Withdrawal | 7.4 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 8 Withdrawal | 6.7 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 14 Withdrawal | 6.9 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 6 Withdrawal | 20.3 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 15 Withdrawal | 15.6 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 9 Withdrawal | 17.0 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 16 Withdrawal | 3.1 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 17 Withdrawal | 7.7 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 3 Withdrawal | 33.1 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 18 Withdrawal | 5.9 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 10 Withdrawal | 13.4 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 0 Withdrawal | 6.1 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 11 Withdrawal | 4.1 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 1 Withdrawal | 29.3 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 7 Withdrawal | 11.9 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 2 Withdrawal | 51.6 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 4 Withdrawal | 29.9 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 12 Withdrawal | 11.7 units on a scale |
| Morphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 5 Withdrawal | 20.1 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 12 Withdrawal | 9.1 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 3 Withdrawal | 9.4 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 10 Withdrawal | 6.3 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 16 Withdrawal | 11.6 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 5 Withdrawal | 11.4 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 6 Withdrawal | 8.6 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 7 Withdrawal | 8.6 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 8 Withdrawal | 13.6 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 9 Withdrawal | 8.6 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 11 Withdrawal | 8.3 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 2 Withdrawal | 13.3 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 13 Withdrawal | 12.7 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 14 Withdrawal | 7.9 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 15 Withdrawal | 12.9 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 17 Withdrawal | 6.7 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 18 Withdrawal | 9.4 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 0 Withdrawal | 2 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 1 Withdrawal | 6.3 units on a scale |
| Buprenorphine | Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS) | Day 4 Withdrawal | 8.6 units on a scale |
Secondary
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.
Time frame: Average mean peak sleep assessed once a week for up to 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morphine | Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI) | Week 2 Withdrawal | 10.3 units on a scale | Standard Error 1.7 |
| Morphine | Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI) | Week 3 Withdrawal | 11.3 units on a scale | Standard Error 2.3 |
| Buprenorphine | Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI) | Week 2 Withdrawal | 5.5 units on a scale | Standard Error 2 |
| Buprenorphine | Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI) | Week 3 Withdrawal | 6.9 units on a scale | Standard Error 1.5 |