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

Phase 2

Recruiting

• Conditions: Pain, Chronic
• Interventions: Drug: Opioid; Drug: Opioid Placebo

• Registration Number: NCT06837857
• Lead Sponsor: Mayo Clinic

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).

Study Timeline

• Study First Submitted: 2025-02-06
• Study First Submitted QC: 2025-02-19
• Study First Posted: 2025-02-20
• Status Verified: 2025-04
• Study Start: 2025-04-16
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-27
• Primary Completion: 2030-12-31
• Study Completion: 2031-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Chronic pain of moderate to severe intensity (greater than or equal to 5 /10 average pain on PEG scale) nearly every day for at least 3 months due to osteoarthritis of the knee OR shoulder
• 65 years of age or older

Exclusion Criteria

• Severe mental health disorder (schizophrenia, bipolar disorder, psychosis, history of suicidality, uncontrolled severe depression or anxiety, severe 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 Too l> 8)
• Residence outside of Minnesota or Wisconsin during opioid intervention period
• Another pain generator that is greater than their knee or shoulder pain
• Anticipated surgery for joint replacement (Knee or shoulder) sooner than 23 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Opioid Group	Opioid	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.
Placebo Group	Opioid Placebo	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.

Primary Outcome Measures

Name	Time	Method
White matter fractional anisotropy (FA) of corpus callosum	Baseline, 12 months	Fractional anisotropy of the corpus callosum, adjusted against baseline value.

Secondary Outcome Measures

Name	Time	Method
Gray matter cortical thickness	Baseline, 12 months	Gray matter cortical thickness from major cortical regions, adjusted baseline values
Digit span memory test	Baseline, 6 weeks, 12 months	The Digit Span memory test requires subjects to repeat series of digits of increasing length. Results are reported as the length of the longest correctly repeated sequence.
White matter fractional anisotropy (FA) of other axonal tracts	Baseline, 12 months	Fractional anisotropy of other white matter structures, adjusted against baseline value.
Subcortical gray matter volumes	Baseline, 12 months	Subcortical gray matter volumes on MRI, adjusted against baseline values
Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) Global-z	Baseline, 6 weeks, 12 months	This battery of tests includes AVLT (auditory verbal learning test), Animal Fluency, TMTB (trail making test B). Results are reported as a standardized z-score, where a higher z-score indicates better cognitive performance, with the score calculated by summing the z-scores of individual cognitive test components that make up the Mayo-PACC
Trailmaking Test A	Baseline, 6 weeks, 12 months	Part A of the Trail Making Test consists of 25 numbered circles distributed over a sheet of paper. The participant is instructed to connect the circles in an ascending order, as quickly as possible, without lifting the pen or pencil from the paper. Results are reported as the number of seconds required to complete the task, higher scores indicate greater impairment.
Mayo Test Drive	Baseline, 6 weeks, 6 month web based, 1 year	Web based self-administered digital cognitive assessment focused on verbal memory, visual matching, and processing speed/executive function

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States