Pain, Chronic
Conditions
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).
Interventions
DRUGOpioid
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.
DRUGOpioid 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.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All parties are masked other than the individual that will be dispensing the drug and preparing the medication (Placebo vs. Opioid).
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| White matter fractional anisotropy (FA) of corpus callosum | Baseline, 12 months | Fractional anisotropy of the corpus callosum, adjusted against baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| White matter fractional anisotropy (FA) of other axonal tracts | Baseline, 12 months | Fractional anisotropy of other white matter structures, adjusted against baseline value. |
| Gray matter cortical thickness | Baseline, 12 months | Gray matter cortical thickness from major cortical regions, adjusted baseline values |
| 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. |
| 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. |
| 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 |
Countries
United States
Outcome results
None listed