Pain, ChronicPhase 2I-COAPNCT06837857
Prescription Opioids, Brain Structure, and Cognition in Older Adults With Chronic Pain
A Phase 2 study testing Opioid in people with Pain, Chronic, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Pain, Chronic
- What is being tested?
- Opioid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2025to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Tami Werts, 507-255-2950, Werts.Tamra@mayo.edu
Nafisseh S Warner, MD
About this study
Official title: 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.
Read the 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
- Being tested
- Opioid, Opioid Placebo
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OpioidDrug
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 PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Opioid Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
White matter fractional anisotropy (FA) of corpus callosum
Fractional anisotropy of the corpus callosum, adjusted against baseline value.
Measured: Baseline, 12 months
Secondary outcomes (7)
White matter fractional anisotropy (FA) of other axonal tracts
Fractional anisotropy of other white matter structures, adjusted against baseline value.
Measured: Baseline, 12 months
Gray matter cortical thickness
Gray matter cortical thickness from major cortical regions, adjusted baseline values
Measured: Baseline, 12 months
Subcortical gray matter volumes
Subcortical gray matter volumes on MRI, adjusted against baseline values
Measured: Baseline, 12 months
Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) Global-z
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
Measured: Baseline, 6 weeks, 12 months
Trailmaking Test A
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.
Measured: Baseline, 6 weeks, 12 months
Digit span memory test
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.
Measured: Baseline, 6 weeks, 12 months
Mayo Test Drive
Web based self-administered digital cognitive assessment focused on verbal memory, visual matching, and processing speed/executive function
Measured: Baseline, 6 weeks, 6 month web based, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2025
- Study start16 Apr 2025
- Primary completion1 Jul 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, ChronicStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nafisseh S. Warner, Mayo Clinic
- Investigators
- Nafisseh Warner, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06837857
- Sponsor's protocol ID
- 24-008096
- Acronym
- I-COAP
- Status last verified
- Jan 2026
- First submitted
- 6 Feb 2025
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging, Cognition, and Opioids in Older Adults With Chronic Pain (I-COAP) Trial
- ClinicalTrials.gov ID
- NCT06837857
- Acronym / sponsor ID
- I-COAP / 24-008096
- Conditions
- Pain, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 16 Apr 2025 (actual)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 20 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opioid Group | Experimental | Drug: OpioidThe 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 | Placebo comparator | Drug: Opioid PlaceboThe 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OpioidSubjects 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. | Drug | Opioid Group |
| Opioid PlaceboSubjects 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. | Drug | Placebo Group |
Primary outcome
White matter fractional anisotropy (FA) of corpus callosum
Time frame: Baseline, 12 months
Fractional anisotropy of the corpus callosum, adjusted against baseline value.
7 secondary outcomes
White matter fractional anisotropy (FA) of other axonal tracts
Time frame: Baseline, 12 months
Gray matter cortical thickness
Time frame: Baseline, 12 months
Subcortical gray matter volumes
Time frame: Baseline, 12 months
Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) Global-z
Time frame: Baseline, 6 weeks, 12 months
Trailmaking Test A
Time frame: Baseline, 6 weeks, 12 months
Digit span memory test
Time frame: Baseline, 6 weeks, 12 months
Mayo Test Drive
Time frame: Baseline, 6 weeks, 6 month web based, 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nafisseh Warner principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Opioid in people with Pain, Chronic, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
White matter fractional anisotropy (FA) of corpus callosum (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.