Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients
|ClinicalTrials.gov Identifier: NCT00295308|
Recruitment Status : Completed
First Posted : February 23, 2006
Last Update Posted : March 20, 2018
- Though the drug buprenorphine effectively treats dependence on opioids like heroin, some abstinent patients relapse to use during treatment. This relapse may be triggered by stress or stressful situations, and buprenorphine probably has no specific protective effect in these situations. Buprenorphine probably also has no specific effect on relapse to cocaine use.
- Research has shown that clonidine, a drug originally prescribed to treat high blood pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse to heroin and cocaine seeking in rats. Researchers are interested in studying whether a combination of clonidine and buprenorphine may be more effective in preventing drug relapse than administering one of the medications alone.
- To determine whether clonidine, given to abstinent patients maintained on buprenorphine, is more effective than placebo in preventing relapse to heroin or cocaine use.
- Individuals between 18 and 50 years of age who are current cocaine or heroin users seeking treatment.
- The study will last up to 36 weeks, with four phases of treatment and a follow-up evaluation. Three times a week, participants will be asked to report illicit drug use and provide urine and breath samples. Throughout the study, participants will receive individual counseling in weekly 40 60 minute sessions. Other samples and tests will be scheduled as required by the study researchers.
- Patients will be stabilized on daily buprenorphine over the first 14 days of the study.
- Weeks 1 8: Participants will receive vouchers for regular substance-free urine samples. Those who successfully complete this phase will continue to the next part of the study.
- Weeks 7 9: Participants will receive either clonidine or placebo along with the buprenorphine. The dose of clonidine will be stabilized during this time.
- Weeks 9 22: Participants will continue to receive either clonidine or placebo along with the buprenorphine. During this part of the study, participants will keep electronic diaries to record drug use or craving and to record data on mood, stress levels, and activity.
- Weeks 23 28: Participants will stop taking the clonidine or placebo, but will continue the buprenorphine treatment. Participants will continue to keep electronic diaries.
- Weeks 29 36: Participants will have the choice of transferring to a community clinic transfer or gradually reducing doses of buprenorphine to end the study.
- Participants will return for a follow-up visit and urine sample 6 months after the end of the study.
|Condition or disease||Intervention/treatment||Phase|
|Opioid-Related Disorders||Drug: Clonidine Drug: Placebo||Phase 1|
Background. Though buprenorphine effectively treats opioid dependence, some abstinent patients relapse to maladaptive use of opioids during treatment. Relapse may be triggered by stress. Rodent studies have demonstrated that stress can induce relapse to heroin and cocaine use (Erb, et al., 1996; Shaham, et al., 1996; Shaham and Stewart, 1995). In a rodent model, stress-induced relapse to heroin and cocaine seeking is blocked by the alpha-2 adrenergic agonist clonidine. In this study, clonidine will be compared to placebo in preventing relapse to opioid abuse in opioid maintained patients who have achieved abstinence while on buprenorphine and contingency management.
Scientific goals. To determine whether clonidine, given to abstinent patients maintained on buprenorphine, prevents relapse to opioid use more effectively than placebo.
Participant population. 300 opioid-dependent outpatients (120 evaluable). Target enrollment will include 40 persent women and 60 percent minorities (mostly African-American).
Experimental design and methods. The study will be a randomized double-blind clinical trial. Two treatment groups will be studied (60/group), one receiving clonidine and the other receiving placebo. Assignment to treatment group will be randomized. All patients will receive buprenorphine daily (8 mg to 24 mg SL) and individual counseling weekly throughout 28 weeks of treatment. In order to establish abstinence prior to clonidine induction, after one week of stabilization on buprenorphine, they will receive contingent vouchers for opioid-negative urine specimens for 8 weeks (weeks 1-8). Patients who are abstinent from illicit opioids during weeks 5 and 6 will be randomized to receive clonidine (0.3 mg oral dose) or clonidine placebo from weeks 9 through 20. Participants who are not abstinent will be switched to methadone for four weeks (usual dose from 50 mg to 100 mg) followed by an eight week methadone taper. Assignment to clonidine or placebo will be double-blind. Weeks 21 and 22 will include a clonidine taper to avoid rebound hypertension. From weeks 23-28, participants will receive buprenorphine and counseling only, and then will be offered assistance to transfer to another program; those who do not transfer will undergo an 8-week buprenorphine taper. The primary outcome measures will be longest duration of opioid abstinence, time to relapse, and the proportion of opioid-negative urine specimens over time during the Intervention phase. In addition, fluctuations in drug use, drug craving, stress, and HIV-risk behaviors such as injection drug use will be assessed via ecological momentary assessment (EMA).
Benefits to participants and/or society. Participants will receive buprenorphine, drug counseling, and contingency-management therapy. The buprenorphine and voucher interventions are likely to reduce participants' use of opioids. Counseling will include reduction of HIV risk behaviors.
Risks to participants. Participants may experience side effects from clonidine, buprenorphine, or methadone and discomfort during withdrawal from each drug. In particular, discontinuation of clonidine may cause rebound hypertension. The EMA component of the study may generate some assessment burden.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients|
|Study Start Date :||November 8, 2005|
|Study Completion Date :||July 30, 2014|
|Experimental: Arm 1||
clonidine up to 0.3 mg/day oral
|Placebo Comparator: Arm 2||
oral capsules daily
- Opiate-negative urine screens [ Time Frame: 38 weeks ]
- HIV risk behaviors [ Time Frame: 38 weeks ]
- Craving [ Time Frame: 18 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00295308
|United States, Maryland|
|National Institute on Drug Abuse|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Kenzie Preston, Ph.D.||National Institute on Drug Abuse (NIDA)|