Trial Outcomes & Findings for A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals (NCT NCT01136356)
NCT ID: NCT01136356
Last Updated: 2017-03-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Average mean peak opioid withdrawal thirty minutes before and after injection assessed up to 59 days
Results posted on
2017-03-03
Participant Flow
The study site was an in-patient research-based clinic affiliated with the Johns Hopkins University School of Medicine.
Participant milestones
| Measure |
Morphine First, Then Buprenorphine
Participants randomized to receive morphine (120 mg/day i.m.) administered in four divide doses for 9 days. Then underwent an 18-day period of spontaneous withdrawal, during which 4 double blind i.m. placebo injections were administered daily. Then administered using buprenorphine (32 mg/day i.m.) with the same time course
|
Buprenorphine First, Then Morphine
Participants randomized to receive buprenorphine (32 mg/day i.m.) administered in four divide doses for 9 days. Then underwent an 18-day period of spontaneous withdrawal, during which 4 double blind i.m. placebo injections were administered daily. Then administered using morphine (120 mg/day i.m.) with the same time course
|
|---|---|---|
|
First Intervention
STARTED
|
6
|
6
|
|
First Intervention
COMPLETED
|
6
|
6
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
First 18-day Withdrawal
STARTED
|
6
|
6
|
|
First 18-day Withdrawal
COMPLETED
|
2
|
6
|
|
First 18-day Withdrawal
NOT COMPLETED
|
4
|
0
|
|
Second Intervention
STARTED
|
2
|
6
|
|
Second Intervention
COMPLETED
|
2
|
6
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
|
Second 18-day Withdrawal
STARTED
|
2
|
6
|
|
Second 18-day Withdrawal
COMPLETED
|
2
|
5
|
|
Second 18-day Withdrawal
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Morphine First, Then Buprenorphine
Participants randomized to receive morphine (120 mg/day i.m.) administered in four divide doses for 9 days. Then underwent an 18-day period of spontaneous withdrawal, during which 4 double blind i.m. placebo injections were administered daily. Then administered using buprenorphine (32 mg/day i.m.) with the same time course
|
Buprenorphine First, Then Morphine
Participants randomized to receive buprenorphine (32 mg/day i.m.) administered in four divide doses for 9 days. Then underwent an 18-day period of spontaneous withdrawal, during which 4 double blind i.m. placebo injections were administered daily. Then administered using morphine (120 mg/day i.m.) with the same time course
|
|---|---|---|
|
First 18-day Withdrawal
Withdrawal by Subject
|
3
|
0
|
|
First 18-day Withdrawal
Physician Decision
|
1
|
0
|
|
Second 18-day Withdrawal
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Within Subject Comparison of Opioid Withdrawal in Opioid Dependent Individuals
Baseline characteristics by cohort
| Measure |
Within Subjects Design
n=12 Participants
Participants received both study drugs (buprenorphine and morphine) in a randomized sequence.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Gender
Female
|
0 Participants
n=5 Participants
|
|
Gender
Male
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Average mean peak opioid withdrawal thirty minutes before and after injection assessed up to 59 daysClinical 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.
Outcome measures
| Measure |
Morphine
n=7 Participants
|
Buprenorphine
n=7 Participants
|
|---|---|---|
|
Mean Peak Opioid Withdrawal Assessed by the Clinical Opiate Withdrawal Scale (COWS)
|
12.6 units on a scale
Interval 0.0 to 48.0
|
1.3 units on a scale
Interval 0.0 to 48.0
|
SECONDARY outcome
Timeframe: Average mean daily peak pain ratings assessed from day 0 to day 18 during the 18 day withdrawal periodVisual 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.
Outcome measures
| Measure |
Morphine
n=7 Participants
|
Buprenorphine
n=7 Participants
|
|---|---|---|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 0 Withdrawal
|
6.1 units on a scale
Interval 0.0 to 100.0
|
2 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 1 Withdrawal
|
29.3 units on a scale
Interval 0.0 to 100.0
|
6.3 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 2 Withdrawal
|
51.6 units on a scale
Interval 0.0 to 100.0
|
13.3 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 3 Withdrawal
|
33.1 units on a scale
Interval 0.0 to 100.0
|
9.4 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 4 Withdrawal
|
29.9 units on a scale
Interval 0.0 to 100.0
|
8.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 5 Withdrawal
|
20.1 units on a scale
Interval 0.0 to 100.0
|
11.4 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 6 Withdrawal
|
20.3 units on a scale
Interval 0.0 to 100.0
|
8.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 7 Withdrawal
|
11.9 units on a scale
Interval 0.0 to 100.0
|
8.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 8 Withdrawal
|
6.7 units on a scale
Interval 0.0 to 100.0
|
13.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 9 Withdrawal
|
17.0 units on a scale
Interval 0.0 to 100.0
|
8.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 10 Withdrawal
|
13.4 units on a scale
Interval 0.0 to 100.0
|
6.3 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 11 Withdrawal
|
4.1 units on a scale
Interval 0.0 to 100.0
|
8.3 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 12 Withdrawal
|
11.7 units on a scale
Interval 0.0 to 100.0
|
9.1 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 13 Withdrawal
|
7.4 units on a scale
Interval 0.0 to 100.0
|
12.7 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 14 Withdrawal
|
6.9 units on a scale
Interval 0.0 to 100.0
|
7.9 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 15 Withdrawal
|
15.6 units on a scale
Interval 0.0 to 100.0
|
12.9 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 16 Withdrawal
|
3.1 units on a scale
Interval 0.0 to 100.0
|
11.6 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 17 Withdrawal
|
7.7 units on a scale
Interval 0.0 to 100.0
|
6.7 units on a scale
Interval 0.0 to 100.0
|
|
Mean Daily Peak Pain Ratings Assessed by the Visual Analog Scale (VAS)
Day 18 Withdrawal
|
5.9 units on a scale
Interval 0.0 to 100.0
|
9.4 units on a scale
Interval 0.0 to 100.0
|
SECONDARY outcome
Timeframe: Average mean peak sleep assessed once a week for up to 8 weeksPittsburgh 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.
Outcome measures
| Measure |
Morphine
n=7 Participants
|
Buprenorphine
n=7 Participants
|
|---|---|---|
|
Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI)
Week 2 Withdrawal
|
10.3 units on a scale
Standard Error 1.7
|
5.5 units on a scale
Standard Error 2
|
|
Mean Peak Sleep Assessed by Pittsburgh Sleep Quality Index (PSQI)
Week 3 Withdrawal
|
11.3 units on a scale
Standard Error 2.3
|
6.9 units on a scale
Standard Error 1.5
|
Adverse Events
All Participants
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Participants
n=12 participants at risk
The adverse events were not specified per drug intervention, therefore, the adverse events per interventions is unknown. The data below references the adverse events recorded by licensed nursing personnel during the participants' 59-day protocol in a residential research unit. All participants (N=7) were randomized to receive either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses each day for 9 days (8 mg of buprenorphine four times per day, or 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 the second opioid administration and spontaneous withdrawal period using the same time course described above.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
33.3%
4/12 • Number of events 13
|
|
Gastrointestinal disorders
Indigestion
|
25.0%
3/12 • Number of events 14
|
|
Eye disorders
Lacrimation Increased
|
16.7%
2/12 • Number of events 11
|
|
General disorders
Chills
|
16.7%
2/12 • Number of events 10
|
|
Psychiatric disorders
Insomnia
|
33.3%
4/12 • Number of events 12
|
|
General disorders
Headache
|
33.3%
4/12 • Number of events 34
|
Additional Information
Eric C. Strain, MD
Johns Hopkins University, School of Medicine
Phone: 410-550-1191
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place