Prescription Opioids, Brain Structure, and Cognition in Older Adults With Chronic Pain (I-COAP)

January 7, 2026 updated by: Nafisseh S. Warner, Mayo Clinic

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Nafisseh S Warner, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.
Placebo Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
White matter fractional anisotropy (FA) of corpus callosum
Time Frame: Baseline, 12 months
Fractional anisotropy of the corpus callosum, adjusted against baseline value.
Baseline, 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, 12 months
Gray matter cortical thickness
Time Frame: Baseline, 12 months
Gray matter cortical thickness from major cortical regions, adjusted baseline values
Baseline, 12 months
Subcortical gray matter volumes
Time Frame: Baseline, 12 months
Subcortical gray matter volumes on MRI, adjusted against baseline values
Baseline, 12 months
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
Baseline, 6 weeks, 12 months
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.
Baseline, 6 weeks, 12 months
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.
Baseline, 6 weeks, 12 months
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
Baseline, 6 weeks, 6 month web based, 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nafisseh Warner, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 16, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 6, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 24-008096

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified summary measures will be made openly available to facilitate future scientific research from this NIA-supported effort. Deidentified individual level data will be available through a controlled access plan, which will require a confidential agreement and institutional review board (IRB) approvals as described in Element 5. MRI data will be linked to the cognitive measures as well as demographic information and clinical measures. In addition to numeric MRI outputs, raw or preprocessed MRI data will be made available in accordance with Brain Imaging Data Structure (BIDS) standards. Non-imaging data including psychometric testing and patient questionnaires will be available in raw form.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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