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

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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:
Information provided by (Responsible Party):
Frances R Levin, New York State Psychiatric Institute

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 During the first week after admission, participants will be withdrawn from their prior opioid analgesic regimen and will be stabilized on one of three doses of buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day).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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
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

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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




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.



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01967641


Locations
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United States, New York
SURC
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
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Principal Investigator: Maria Sullivan, MD Columbia University

Additional Information:
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Responsible Party: Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01967641     History of Changes
Other Study ID Numbers: #6269R
DA020448-05 ( Other Grant/Funding Number: NIH )
First Posted: October 23, 2013    Key Record Dates
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:
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Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Analgesics, Opioid
Buprenorphine
Buprenorphine, Naloxone Drug Combination
Naloxone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists