Clinical trial NCT01967641
Conditions: Opioid Dependence
Keywords: opioid dependence opioid abuse suboxone prescription pain medications
Sponsor: New York State Psychiatric Institute
Start date: 2005-11-01; Completion date: 2011-06-01
Enrollment: 51 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In this study, we will assess opioid self-administration in a laboratory setting in persons with pain who have a history of opioid abuse. Participants diagnosed with mild to moderate pain will be admitted to hospital for 7 weeks and transitioned from their baseline prescription opioid to a standing daily dose of Suboxone (buprenorphine/naloxone combination). During this maintenance period, participants will have the opportunity in a laboratory setting to self-administer oxycodone; subjective responses as well as analgesic, physiological and performance effects will be measured. In the second phase of this study, the same patients who participated in the inpatient phase will be followed on an outpatient basis while maintained on Suboxone for 12 weeks. . The hypotheses of this study are that (1) higher progressive ratio break-point values for oxycodone, higher subjective ratings of euphoria, and less pain relief will predict early relapse to opioid abuse; (2) the abuse liability measures will be more strongly correlated with relapse than the pain measures; (3) subjective ratings of euphoria will increase and of pain will decrease in an oxycodone dose-dependent manner (i.e. euphoria will increase and pain will decrease as dose increases); and (4) experimentally induced pain will decrease in an oxycodone dose-dependent manner.

Detailed description:
All participants will be admitted to the GCRU, the SRU, or the CRR and maintained on sublingual Bup/Ntx. During the first week after admission, participants will be withdrawn from their prior opioid analgesic regimen and will be stabilized on one of three doses of buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day). Participants will be treated for emergent withdrawal symptoms with supplemental supplemental medications (clonidine, clonazepam, compazine, ketorolac tromethamine, hydroxyzine, ranitidine, ondansetron, zolpidem) until withdrawal symptoms have dissipated, based on self-report and observer ratings. Each buprenorphine dose will be administered in equal divided doses according to a QID dosing schedule, and each dose will be maintained for a two-week period (one week of stabilization followed by one week of laboratory testing). Thus, stabilization will occur during Weeks 1, 3, and 5; testing will occur in Weeks 2, 4, and 6. Participants may receive an unaccompanied pass of up to 72 hours during Weeks 3 and 5 to attend to family obligations. Participants will be informed that urine toxicology screens will be conducted upon their return to the hospital, and that testing positive for drugs other than the study medication may result in discharge from the study. The order of administration of these three doses will vary among subjects in a randomized manner. At the completion of laboratory testing in Week 6, participants will be stabilized on 16 mg of buprenorphine. This final week of stabilization ensures that (1) any acute effects of high-dose oxycodone administration in the laboratory have dissipated and do not affect opioid dependence level; and (2) participants have sufficient opportunity to stabilize on the dose of buprenorphine on which they will be maintained during the outpatient phase.

Participants whose pain is not adequately relieved by Suboxone (buprenorphine/naloxone) will we removed from the study by the investigators. A criterion for dropout during the inpatient phase will be: clear decline in functional status, such as sustained worsening of mobility or marked decline in level of activity. In the event that average daily pain level worsens from baseline by 30% or more (e.g. 6/10 to 9/10), a clinical evaluation will be performed to consider whether the participant should be removed from the protocol, or should be allowed to continue to participate. The clinical determination will include an assessment of whether pain has improved throughout the inpatient stay as a range of doses are tested.

During the subsequent outpatient phase medication will be dispensed on a weekly basis and will consist of (1) a standing maintenance dose of 16 mg Suboxone (buprenorphine/naloxone), and (2) doses of Suboxone to be taken on a prn basis for breakthrough pain (prn doses will not exceed 25% of the total daily standing dose). Patients will report to the Substance Use Research Center (SURC) twice per week for 12 weeks for clinical visits.

Arms: arm 1: Buprenorphine/naloxone (Bup/Nx; Suboxone sublingual tablets, Reckitt Benckiser) will be administered sublingually at daily doses of 2/0.5, 8/2 mg, and 16/4 mg, which are within the recommended dose range for treating both pain and opioid abuse. The total daily dose will be divided and administered on a QID dosing regimen (0.5/0.125, 2/0.5, and 4/1 mg QID at 0830, 1230, 1730, 2130). Each participant will be tested with all three doses in random order for two weeks at each dose (one week of stabilization followed by one week of testing). Following completion of the 7-week inpatient phase, participants will be followed at the Substance Use Research Center (SURC) and maintained on 16/4 mg Bup/Nx.
Interventions: intervention 1: buprenorphine/naloxone combination
Intervention descriptions: intervention 1: Buprenorphine/naloxone (Bup/Nx; Suboxone sublingual tablets, Reckitt Benckiser) will be administered sublingually at daily doses of 2/0.5, 8/2 mg, and 16/4 mg, which are within the recommended dose range for treating both pain and opioid abuse. The total daily dose will be divided and administered on a QID dosing regimen (0.5/0.125, 2/0.5, and 4/1 mg QID at 0830, 1230, 1730, 2130). Each participant will be tested with all three doses in random order for two weeks at each dose (one week of stabilization followed by one week of testing). Following completion of the 7-week inpatient phase, participants will be maintained on 16/4 mg Bup/Nx.

Protocol documents: