Clinical trial NCT03912298: Opioid Taper Study
Official title: Effect of Opioid Taper on Pain Responses in Patients With Chronic Pain
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Pain
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institutes of Health (NIH)
First posted: 2019-04-11
Enrollment: 7
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The sample will consist of 25 male and female adults with chronic neuropathic pain on opioid therapy and preparing to voluntarily undergo a prescribed opioid taper.

Brief summary: The purpose of this study is to determine the effect of opioid taper on pain sensitivity in patients with chronic pain. In a well-characterized sample of men and women with chronic neuropathic pain on high-dose opioid therapy, experimental pain responses (cold-pressor, quantitative sensory testing) will be serially described over the course of and following an individualized opioid taper. In addition, functional improvements and subject-level predictors of response will be described.

Detailed description: The overall Specific Aim of this proposal is to determine the effect of opioid taper on pain sensitivity in patients with chronic pain. Specifically, in a well-characterized sample of men and women with chronic neuropathic pain and receiving high-dose opioid therapy (\>100mg morphine equivalents/day \[MED\]), experimental pain responses will be serially described over the course of an individualized opioid taper to a safer dose of 90mg MED for up to 12 months. Changes will be inspected within-subject over time, and pain perception will be measured with two valid and reliable experimental pain induction techniques commonly used to measure OIH (cold-pressor, quantitative sensory testing); in addition, related functional improvements and subject-level predictors of response will be described.

Hypothesis 1. Subjects undergoing opioid taper will have improved pain responses over time compared to within-subject baseline as measured by cold-pressor and quantitative sensory pain testing.

Hypothesis 2. Improvements in experimental pain responses will be positively related to improved functional outcomes compared to within-subject baseline as measured by the PROMIS physical, mental and social health measures.

Hypothesis 3. Degree of improvement in experimental pain responses related to opioid taper will be predicted by demographic, pain, and opioid use history characteristics of the subject.

Data showing that pain perception improves as opioids are withdrawn would provide an evidence-based, mechanistic rationale for opioid taper in patients with chronic pain and have the potential to support a sea-change in opioid prescription practices. In that ongoing opioid therapy brings with it significant health risks for the patient and the community, it is critical that empirical evidence of its efficacy be demonstrated to balance the benefits with the risks of adverse events, potential misuse and abuse, and patient safety.

Eligibility criteria: Inclusion Criteria:

1. between ages of 21-70;
2. documented chronic neuropathic non-malignant pain condition of at least one year duration;
3. on \>100mg/day MED for at least 6 months;
4. have fully engaged in all prescribed non-opioid pain management treatments;
5. willing to undergo prescribed opioid taper;
6. otherwise in good physical and mental health, or in the care of a physician who is willing to take responsibility for such treatment;
7. able to understand the purpose and instructions of the study, and provide informed consent as approved by the University of Pennsylvania IRB.

Exclusion Criteria:

1. meet diagnostic criteria for an active substance use disorder other than nicotine;
2. be acutely psychotic, severely depressed, and/or in need of inpatient psychiatric treatment,
3. have a neurological or psychiatric illness that would affect pain responses, including anxiety disorders;
4. have a history of heart disease, stroke, or a pacemaker or uncontrolled high blood pressure. Good cardiovascular health is stipulated to ensure subjects can tolerate the sympathetic nervous system responses associated with the pain induction procedures.

Primary outcomes:
measure: Pain Perception Measured Using the Cold-pressor Test (CPT)
timeFrame: up to one year (length of taper individualized and varies)
measure: Conditioned Pain Modulation Measured Using the Quantitative Sensory Testing (QST)
timeFrame: up to one year (individualized, variable taper length)
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Pain Medicine Center Tuttleman Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Margaret A Compton, RN, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dowell D, Haegerich TM. Changing the Conversation About Opioid Tapering. Ann Intern Med. 2017 Aug 1;167(3):208-209. doi: 10.7326/M17-1402. Epub 2017 Jul 11. No abstract available.
citation: Peles E, Schreiber S, Hetzroni T, Adelson M, Defrin R. The differential effect of methadone dose and of chronic pain on pain perception of former heroin addicts receiving methadone maintenance treatment. J Pain. 2011 Jan;12(1):41-50. doi: 10.1016/j.jpain.2010.04.009. Epub 2010 Jun 19.
citation: Wang H, Fischer C, Chen G, Weinsheimer N, Gantz S, Schiltenwolf M. Does long-term opioid therapy reduce pain sensitivity of patients with chronic low back pain? Evidence from quantitative sensory testing. Pain Physician. 2012 Jul;15(3 Suppl):ES135-43.
citation: Compton P, Halabicky OM, Aryal S, Badiola I. Opioid Taper is Associated with Improved Experimental Pain Tolerance in Patients with Chronic Pain: An Observational Study. Pain Ther. 2022 Mar;11(1):303-313. doi: 10.1007/s40122-021-00348-8. Epub 2022 Jan 12.