Prescription Opioids, Brain Structure, and Cognition in Older Adults With Chronic Pain

NCT ID: NCT06837857

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-16
• Study Completion Date: 2029-12-31

Brief Summary

The purpose of this study is to determine whether exposure to prescription opioids is associated with brain structural changes on magnetic resonance imaging (MRI), with the primary outcome of white matter integrity as measured by fractional anisotropy of the corpus callosum.

Detailed Description

The investigators will recruit 200 adults aged 65 years and older with chronic pain of the knee or shoulder. Each will receive an individualized multimodal pain treatment pathway for 6-weeks - for half of participants this will include a prescription opioid; the other half will receive an identical placebo. After 6 weeks, participants will undergo opioid/placebo taper. The investigators will obtain neuroimaging (MRI), psychometric/cognitive testing, pain scores, and several exploratory patient-reported outcomes at several time-points: before the intervention (all tests), at 6 weeks (all tests except MRI), 6-month phone call (only phone based patient reported outcomes- no MRI), and at 1 year (all tests).

Conditions

Pain, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Opioid Group

The participant will be plugged into an individualized comprehensive tiered pain plan that can include: Tier one (Acetaminophen, NSAIDS, Topicals, TENS unit, Massage, Acupuncture, Physical therapy. Tier two (Cognitive behavioral therapy, joint injections, nerve ablations, peripheral nerve stimulators) and less commonly Tier three (duloxetine, gabapentin). This is modeled after clinical practice. The participants will additionally receive prescription opioids for 6 weeks.

Group Type: EXPERIMENTAL

Opioid

Intervention Type: DRUG

Subjects will receive oral oxycodone as needed for pain which will be titrated weekly based on pain response, adverse effects, and patient preference. Subjects with intolerance to oxycodone will receive the equivalent dosing of morphine as an alternative.

Placebo Group

The participant will be plugged into an individualized comprehensive tiered pain plan that can include: Tier one (Acetaminophen, NSAIDS, Topicals, TENS unit, Massage, Acupuncture, Physical therapy. Tier two (Cognitive behavioral therapy, joint injections, nerve ablations, peripheral nerve stimulators) and less commonly Tier three (duloxetine, gabapentin). This is modeled after clinical practice. The participants will additionally receive a prescription opioid placebo for 6 weeks.

Group Type: PLACEBO_COMPARATOR

Opioid Placebo

Intervention Type: DRUG

Subjects will receive a placebo capsule identical to oxycodone, which will similarly be titrated weekly. Subjects with intolerance to the first placebo will receive another placebo capsule identical to morphine.

Interventions

Opioid

Subjects will receive oral oxycodone as needed for pain which will be titrated weekly based on pain response, adverse effects, and patient preference. Subjects with intolerance to oxycodone will receive the equivalent dosing of morphine as an alternative.

Intervention Type: DRUG

Opioid Placebo

Subjects will receive a placebo capsule identical to oxycodone, which will similarly be titrated weekly. Subjects with intolerance to the first placebo will receive another placebo capsule identical to morphine.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 65 years of age or older
• Pain for longer than 3 months (chronic)
• Moderate to severe pain nearly every day (averaged PEG score >5)
• Persistent pain despite use of >1 analgesic (Tylenol, Ibuprofen, lidocaine patch, etc)

Exclusion Criteria

• Untreated severe/uncontrolled Mental health (schizophrenia, bipolar disorder, psychosis, history of suicidality, depression or anxiety, PTSD)
• Severe liver (cirrhosis) or kidney disease (ESRD on dialysis or GFR< 30)
• Cognitive impairment (Kokmen Short Test of Mental Status score < 29)
• Life expectancy < 12 months
• Contraindications to MRI
• Non-English speaking
• Opioid use within the past 6 months
• Contraindications or previous intolerance to prescription opioids
• Substance use disorder or high-risk for opioid-related adverse effects (Opioid Risk Tool ≥ 8)
• Residence outside of Minnesota or Wisconsin during opioid intervention period
• Another pain generator that is greater than their knee or shoulder or low back pain
• Anticipated surgery for joint replacement (Knee or shoulder) sooner than 3 months.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Nafisseh S. Warner

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nafisseh Warner

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Tami Werts

Role: primary

Werts.Tamra@mayo.edu

507-255-2950

Other Identifiers

24-008096

Identifier Type: -

Identifier Source: org_study_id