Prescription Opioid Abuse Among Pain Patients: Predictors of Relapse (PAIN)

• ClinicalTrials.gov Identifier: NCT01967641
• Recruitment Status: Completed
• First Posted: October 23, 2013
• Results First Posted: June 15, 2018
• Last Update Posted: April 24, 2019
• Sponsor: New York State Psychiatric Institute
• Information provided by (Responsible Party): Frances R Levin, New York State Psychiatric Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Opioid Dependence	Drug: buprenorphine/naloxone combination	Phase 2

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 During the first week after admission, participants will be withdrawn from their prior opioid analgesic regimen and will be stabilized on one of three doses of buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day).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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Following induction, patients were stabilized beginning on Day 2 on one of three blinded doses of buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day) for a week then underwent laboratory testing for a second week. Each blinded buprenorphine dose was administered in equal divided doses according to a QID dosing schedule, and each dose was maintained for a two-week period, with the second week including laboratory testing.
• Primary Purpose: Treatment
• Official Title: Prescription Opioid Abuse Among Pain Patients: Predictors of Relapse
• Study Start Date: November 2005
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: buprenorphine/naloxone combination; 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.

Drug: buprenorphine/naloxone combination; 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.; Other Name: Suboxone

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Retained in Study [ Time Frame: week 19 ]
   Retention was number of participants retained at study end (Week 19).

Secondary Outcome Measures :

1. Number of Participants Abstinent From Opioids [ Time Frame: at week 19 or length of study participation ]
   Relapse was number of participants with opioid-negative urine toxicology in last week of study participation.
2. Pain Measurement [ Time Frame: assessed twice weekly during course of 19 weeks or length of participation, only screening and last assessment reported. ]
   The primary pain measure was the Pain Assessment and Documentation Tool (PADT). Total score ranging from 0-11 reported. Higher score considered indicative of more pain. Lower score is indicative of less pain.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. DSM-IV criteria for opioid abuse and prescription opioid physical dependence
2. 18-65 years of age
3. Stable weight (<10% change in 3 months) and stable physical health
4. Chronic pain syndrome (e.g., osteoarthritic pain or chronic lower back pain with/without history of surgery) of moderate (4-7) average daily pain of 6+ months duration; opioid medication maintenance for 6+ months
5. Seeking treatment for chronic pain
6. Must be expected to achieve a good analgesic effect from buprenorphine

Exclusion Criteria:

1. DSM-IV untreated Axis I disorders (e.g. MDD, BAD, psychotic disorders, eating disorders) requiring treatment
2. Regular consumption of more than 500 mg caffeine daily
3. Primary pain diagnosis of neuropathic pain, malignant pain, or headache
4. History of allergy, adverse reaction, or sensitivity to opioids, including buprenorphine
5. Pregnancy, lactation, or history of having given birth or had abortion or miscarriage within the last six months, or unwillingness to use an effective method of birth control (e.g. condoms, birth control pills, abstinence)
6. Psychotropic medications which would potentially interfere with study procedures
7. Inability to read or understand the self-report assessment forms unaided
8. Use of medications known to interfere with buprenorphine metabolism, such as disulfiram, neuroleptics, azole antifungals (e.g. ketoconazole), macrolide antibiotics (e.g. erythromycin), and HIV protease inhibitors (e.g. ritonavir, indivair, and saquinavir)
9. Methadone-dependent
10. Current heroin dependence
11. Current buprenorphine maintenance
12. History of failed treatment with buprenorphine maintenance for pain
13. Acute hepatitis with elevated liver function tests (i.e. AST and ALT > 3 times the upper limit of normal) or impaired renal function (creatinine > 1.2 )
14. Any medical condition that might interfere with the study or significantly increase the medical risks of study participation
15. Participant is currently receiving any investigational drug or has used any investigational drug within 30 days of study entry
16. History of significant cardiovascular disease, such as coronary artery disease or hypertension requiring more than two anti-hypertensive agents
17. History of insulin-dependent diabetes
18. Body mass index of <18.5 or > 35.0

Contacts and Locations

Locations

United States, New York

SURC

New York, New York, United States, 10032

Sponsors and Collaborators

New York State Psychiatric Institute

Investigators

• Principal Investigator: Maria Sullivan, MD; Columbia University

More Information

Additional Information:

The Substance Treatment and Research Service of Columbia University (STARS) provides free and confidential treatment of substance abuse in the context of a research treatment clinical trial. 

• Responsible Party: Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01967641
• Other Study ID Numbers: #6269R; DA020448-05 ( Other Grant/Funding Number: NIH )
• First Posted: October 23, 2013
• Results First Posted: June 15, 2018
• Last Update Posted: April 24, 2019
• Last Verified: April 2019

Keywords provided by Frances R Levin, New York State Psychiatric Institute:

opioid dependence; opioid abuse; suboxone; prescription pain medications

Additional relevant MeSH terms:

Opioid-Related Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Narcotic Antagonists