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

NCT06837857 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-008096
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Chronic

Outcome Measures

Primary Outcomes (1)

• White matter fractional anisotropy (FA) of corpus callosum

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

  Baseline, 12 months

Secondary Outcomes (7)

• White matter fractional anisotropy (FA) of other axonal tracts

  Baseline, 12 months

• Gray matter cortical thickness

  Baseline, 12 months

• Subcortical gray matter volumes

  Baseline, 12 months

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

  Baseline, 6 weeks, 12 months

• Trailmaking Test A

  Baseline, 6 weeks, 12 months

Study Arms (2)

Opioid Group

EXPERIMENTAL

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.

Drug: Opioid

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Opioid Placebo

Interventions

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 Group

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.

Placebo Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Interventions

Analgesics, Opioid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses

Study Officials

• Nafisseh Warner

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties are masked other than the individual that will be dispensing the drug and preparing the medication (Placebo vs. Opioid).
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 20, 2025
• Study Start: April 16, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Scientific data will be deposited into the repository at the time of publication or the end of the award period, which comes first. Data will be preserved for a minimum of 5 years following the end of the grant period.
• Access Criteria: De-identified datasets from this research study will be made available in accordance with the NIH Aging Research Biobank. Additional requests will be considered to the extent permissible under our IRB approvals, and local, state and federal laws and regulations, including the Privacy Rule. Additional requests for data should be directed to the study's Principal Investigators, who will evaluate the requests in a timely manner. Incoming proposals will be screened to ensure that the requests did not overlap or conflict with the funded efforts of this project. Approved requests will require a signed data use agreement and IRB approval to ensure that the usual procedures for participant protection are followed.

Locations

US (1)