Prescription Opioid Abuse Among Pain Patients: Predictors of Relapse
Condition: Opioid Dependence
MeSH terms: Opioid-Related Disorders
Intervention: buprenorphine/naloxone combination
Intervention description: 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.
Intervention MeSH terms: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: opioid dependence; opioid abuse; suboxone; prescription pain medications

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.
    

Eligibility 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