Opioid Dependence, Opioid Detoxification, Opioid Withdrawal
Conditions
Keywords
opioid dependent, detoxification, buprenorphine, suboxone, opiate
Brief summary
This study involves inducting treatment seeking opioid dependent participants onto buprenorphine. Once the participant reaches a stable dose they will receive either placebo or gabapentin to determine if gabapentin helps ease withdrawal symptoms while the participant undergoes a 10-day buprenorphine detoxification.
Interventions
DRUGBuprenorphine
Induction onto buprenorphine to a stable dose of 12mg/day. Then induction onto either 0 or 1600mg of gabapentin. Once the maintenance dose of gabapentin is reached a 10-day buprenorphine detoxification will begin.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Availability to attend clinic 6 days a week for approximately 30-60 minutes. * Participants must fulfill DSM-IV criteria for opioid dependence. These criteria will be ascertained in the following manner: the physician will determine whether the individual is appropriate based on several clinical assessments that are routinely employed by methadone program physicians, including history and severity of opioid use, presence of track marks, prior treatment history, self-reported and/or observed signs and symptoms of opioid withdrawal. If any individual's degree of opioid dependence is questionable, that person will be excluded from further consideration as a participant. * Participants must submit a urine negative for drugs of abuse other than opioids prior to starting the study.
Exclusion criteria
* Unstable medical condition or stable medical condition that would interact with study medications or participation. * History of major psychiatric disorder (psychosis, schizophrenia, bipolar, depression) * Pregnancy or plans to become pregnant or inadequate birth control (adequate birth control includes abstinence, condoms, birth control pills, etc). * Present or recent use of over-the-counter psychoactive drug, prescription psychoactive drug or drug (including Maalox) that would have major interaction with drugs to be tested. * Liver function tests greater than 3 times normal, BUN and Creatinine outside normal range, or thyroid function tests outside normal range. * EKG abnormalities including but not limited to: bradycardia (\<60 bpm); prolonged QTc interval (\>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block. * Physical dependence on alcohol or drugs other than opioids or tobacco (as determined by physician assessment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Illicit Opioid Use as Determine by Urine Dipsticks | 3x weekly during wks 3 and 4 | urine data are from those obtained during the buprenorphine taper |
Countries
United States
Participant flow
Recruitment details
Thirty treatment-seeking opioid-dependent individuals were recruited from Central Arkansas by ads, word-of-mouth and referrals in October 2010 and January 2011-December of 2011. An experienced research staff member obtained informed consent interviewed subjects in a private office on the 4th floor of the Psychiatric Research Institute.
Pre-assignment details
On Tuesday of Week 1, participants were randomized into treatment groups based on withdrawal symptoms score, sex and primary opioid of abuse using an urn randomization procedure. This was done to ensure that groups are balanced with respect to potential prognostic factors.
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin Buprenorphine will be given along with 2 capsules of gabapentin in the morning and 2 take-home capsules of gabapentin for night. | 11 |
| Placebo Buprenorphine will be given, with 2 capsules of placebo in the morning and 2 take-home capsules of placebo in the evening | 13 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Buprenorphine+Gabapentin/Plac Induction | Lost to Follow-up | 2 | 1 |
| Buprenorphine+Gabapentin/Plac Induction | Physician Decision | 1 | 0 |
| Buprenorphine Taper | noncompliance - missed medication | 1 | 1 |
| Gabapentin Taper | noncompliance - missed medications | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Gabapentin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 24 Participants |
| Age Continuous | 30.31 years STANDARD_DEVIATION 10.62 | 29.00 years STANDARD_DEVIATION 11.05 | 29.71 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 13 participants | 11 participants | 24 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 16 | 4 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Illicit Opioid Use as Determine by Urine Dipsticks
urine data are from those obtained during the buprenorphine taper
Time frame: 3x weekly during wks 3 and 4
Population: Those who started the bup detox (N=24) excluding 1 subjects' data in the gabapentin group due to evidence of noncompliance with medication procedures and diversion (N=1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Illicit Opioid Use as Determine by Urine Dipsticks | 13.64 % of urines positive for opioids | Standard Error 5.69 |
| Placebo | Illicit Opioid Use as Determine by Urine Dipsticks | 32.56 % of urines positive for opioids | Standard Error 9.93 |
Comparison: test null hypothesis that gbp and pla did not differ in terms of opioid-positive urines during the buprenorphine detox.~For the analysis, data from 2 participants in the GBP groups were excluded due to evidence of medication diversion (N=1) and not being maintained on the 1600 mg/day dose of GBP (N=1).p-value: 0.035Mixed Models Analysis