Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients
|First Received Date ICMJE||February 22, 2006|
|Last Updated Date||September 18, 2014|
|Start Date ICMJE||November 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Opiate-negative urine screens [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE
||Opiate-negative urine screens|
|Change History||Complete list of historical versions of study NCT00295308 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients|
|Official Title ICMJE||Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients|
- 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.
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 ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Condition ICMJE||Opioid-Related Disorders|
|Study Arm (s)||
|Publications *||Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL. Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment. Am J Psychiatry. 2015 Aug 1;172(8):760-7. doi: 10.1176/appi.ajp.2014.14081014. Epub 2015 Mar 17.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||300|
|Completion Date||July 2014|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Taking contraindicated medications-
Family history of sudden cardiac death at age < 50
Lab Test and Lab Values:
WBC* < 1,500 > 13,000 #/CUMM
HCT < 33 > 49 Percent
Platelets < 100 > 500 K/CUMM
Sodium < 132 > 149 MEQ/L
Potassium < 3.5 > 5.2 MEQ/L
Calcium < 8.4 > 10.5 MG/DL
Magnesium < 1.3 > 3 MG/DL
BUN > 35 MG/DL
Cr< TAB> > 2.0 MG/DL
Alk Phos< TAB> > 200 U/L
AST< TAB> > 200 U/L
ALT< TAB> > 200 U/L
GGT< TAB> > 400 U/L
Albumin< TAB> < 3 GM/DL
Total bilirubin > 2.0 MG/DL
Direct bilirubin > 0.4 MG/DL
TSH< TAB> < 0.27 > 4.2 UIU/ML
*Leukocytosis will prompt further investigation before clearance.< TAB>
|Ages||18 Years to 50 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00295308|
|Other Study ID Numbers ICMJE||999906407, 06-DA-N407|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute on Drug Abuse (NIDA)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 2014|
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