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

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01967641
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arm: 1
• Duration (Months): 67
• Patients Per Site Per Month: 0.8

Study Details

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 During the first week after admission, participants will be withdrawn from their prior opioid analgesic regimen and will be stabilized on one of three doses of buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day).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
• 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: Nov 1, 2005
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 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 Names: Suboxone

Outcome Measures

Primary Outcome Measures

1. Number of Participants Retained in Study [week 19]

   Retention was number of participants retained at study end (Week 19).

Secondary Outcome Measures

1. Number of Participants Abstinent From Opioids [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	SURC	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Maria Sullivan, MD, Columbia University

Study Documents (Full-Text)

None provided.

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.

Publications

None provided.

• 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
• First Posted: Oct 23, 2013
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Frances R Levin, Director of Substance Use Disorder, New York State Psychiatric Institute: opioid dependence; opioid abuse; suboxone; prescription pain medications
• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone

Study Results

Participant Flow

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Fifty-one (51) participants met inclusion/exclusion criteria and were randomized to a starting dose of buprenorphine/naloxone in the study (three doses were tested for 2 weeks at each dose).
Period Title: Randomized
STARTED	51
COMPLETED	43
NOT COMPLETED	8
Period Title: Randomized
STARTED	43
COMPLETED	31
NOT COMPLETED	12
Period Title: Randomized
STARTED	31
COMPLETED	18
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Fifty-one (51) participants met inclusion/exclusion criteria and were randomized to a starting dose of buprenorphine/naloxone in the study (three doses were tested for 2 weeks at each dose).
Overall Participants	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.5 (9.5)
Sex: Female, Male (Count of Participants)
Female	23 45.1%
Male	28 54.9%
Race/Ethnicity, Customized (participants) [Number]
Caucaisan	23 45.1%
African American	15 29.4%
Hispanic	11 21.6%
unknown	2 3.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Retained in Study
Description	Retention was number of participants retained at study end (Week 19).
Time Frame	week 19

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Fifty-one (51) participants met inclusion/exclusion criteria and were randomized to a starting dose of buprenorphine/naloxone in the study (three doses were tested for 2 weeks at each dose).
Measure Participants	51
Number [participants]	18 35.3%

2. Secondary Outcome

Title	Number of Participants Abstinent From Opioids
Description	Relapse was number of participants with opioid-negative urine toxicology in last week of study participation.
Time Frame	at week 19 or length of study participation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Thirty-one (31) participants who initiated outpatient phase
Measure Participants	31
Number [participants]	17 33.3%

3. Secondary Outcome

Title	Pain Measurement
Description	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.
Time Frame	assessed twice weekly during course of 19 weeks or length of participation, only screening and last assessment reported.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Thirty-one (31) participants who initiated outpatient phase
Measure Participants	31
screening	6.1 (1.9)
end of study	4.3 (0.65)

Adverse Events

Arm/Group Title	Buprenorphine/Naloxone Combination
Arm/Group Description	Fifty-one (51) participants met inclusion/exclusion criteria and were randomized to a starting dose of buprenorphine/naloxone in the study (three doses were tested for 2 weeks at each dose).
All Cause Mortality
	Buprenorphine/Naloxone Combination
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Buprenorphine/Naloxone Combination
	Affected / at Risk (%)	# Events
Total	7/51 (13.7%)
Cardiac disorders
chest pain	1/51 (2%)
General disorders
Hospitalization for rehydration/nutrition	1/51 (2%)
Somnolence, BP drop; intubated in ER;	1/51 (2%)
leg pain/swelling	1/51 (2%)
Psychiatric disorders
ER presentation for altered mental status after ingesting sleeping pills	1/51 (2%)
Renal and urinary disorders
Urinary tract infection	1/51 (2%)
Skin and subcutaneous tissue disorders
cellulitis	1/51 (2%)
Other (Not Including Serious) Adverse Events
	Buprenorphine/Naloxone Combination
	Affected / at Risk (%)	# Events
Total	0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.