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NCT Number: NCT06837857

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

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.

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Key information

Conditions

Pain, Chronic Chronic Pain Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location status: Recruiting

Location contact

Nafisseh S Warner, MD

PRINCIPAL_INVESTIGATOR

Tami Werts

CONTACT

[email protected]

507-255-2950

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Opioid

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.

Opioid Placebo

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.

Primary outcomes

  1. White matter fractional anisotropy (FA) of corpus callosum

    Time frame: Baseline, 12 months

    Fractional anisotropy of the corpus callosum, adjusted against baseline value.

Secondary outcomes

  1. White matter fractional anisotropy (FA) of other axonal tracts

    Time frame: Baseline, 12 months

    Fractional anisotropy of other white matter structures, adjusted against baseline value.

  2. Gray matter cortical thickness

    Time frame: Baseline, 12 months

    Gray matter cortical thickness from major cortical regions, adjusted baseline values

  3. Subcortical gray matter volumes

    Time frame: Baseline, 12 months

    Subcortical gray matter volumes on MRI, adjusted against baseline values

  4. Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) Global-z

    Time frame: 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

  5. Trailmaking Test A

    Time frame: 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.

  6. Digit span memory test

    Time frame: 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.

  7. Mayo Test Drive

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Official study title

Imaging, Cognition, and Opioids in Older Adults With Chronic Pain (I-COAP) Trial

Acronym: I-COAP

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Feb 20, 2025
Registry last updated
Jan 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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