Osteoarthritis, Pain
Conditions
Keywords
placebo, pain, osteoarthritis
Brief summary
This is a two week,single-blind study evaluating pain response and changes in brain imaging upon treatment with placebo in people with knee OA.
Detailed description
In this study, all the participants will be receiving placebo. However this study will be single blinded in that participants will be told that they will be given a pill that may or may not help with their pain. The researcher, however, will know that all participants are receiving placebo At the initial visit, participants will undergo screening to determine that they meet all inclusion and exclusion criteria. They will sign consent and then complete pain assessment instruments as well as one high resolution anatomical scan (T1) and one functional scan (a resting scar) in a 3 Tesla magnet. A single scanning session comprised of a 10 minute functional scan (a resting scan) will be done two weeks from the first scan and pain assessment instruments will be completed at this visit as well. After finishing this second scan (done two weeks after the initial scan), the participants will have completed the study.
Interventions
DRUGDuloxetine
Duloxetine Delayed-Release Capsules: 30mg/day for 1 week ; 60mg/day for the remaining time
DRUGPlacebo Oral Tablet
Lactose capsule
Sponsors
Eli Lilly and Company
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age: 40-85 years * ACR criteria for OA including Kellgren-Lawrence radiographic OA grades II-IV * VAS pain score \>5/10 within 48 hrs of the phone screen and visit 1 (Screening) * Knee OA for a minimum of 12 months * Need for daily pain medication to manage symptoms of OA
Exclusion criteria
* Currently taking MAO inhibitors or any centrally acting drug for analgesia * Narrow angle glaucoma * Uncontrolled hypertension * Co-existing inflammatory arthritis, fibromyalgia or other chronic pain state * If a female, pregnant, trying to become pregnant, or lactating * Major depressive disorder * Substantial alcohol use or history of significant liver disease * Diabetes, type 1 or type 2 * Condition in which the Investigator believes would interfere with the subject's ability to comply with study instructions, or might confound the interpretation of the study results or put the subject at undue risk * Standard MRI safety exclusions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Regional Gray Matter Density | 2 weeks | Gray matter density (GMD) of the prefrontal cortex region identified as placebo biomarker. Placebo responders/non-responders were identified based on the VAS score. A minimum of 20% decrease in VAS score was needed to be qualified as responders. GMD is a value between 0 and 1 representing the intensity of every brain voxels. The GMD of the prefrontal cortex region represent the average GMD of every voxels in this region. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC Pain Index | 2 weeks | Osteoarthritis (OA) specific pain and quality of life index (the Western Ontario and McMaster Universities Osteoarthritis Index WOMAC). The WOMAC score is from 0 to 96 where 0 represent no pain and quality of life impairment due to OA and 96 represent the worst pain and quality of life impairment due to OA. The outcome is reported as the percent change from baseline to end of treatment (2 weeks). |
| Overall Brain Neocortical Gray Matter Volume | 2 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo capsule
placebo: lactose containing capsule | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 4 |
Baseline characteristics
| Characteristic | Placebo |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 56.88 years STANDARD_DEVIATION 5.68 |
| Gender Female | 9 Participants |
| Gender Male | 8 Participants |
| Pain (Visual Analogue Score, VAS) | 7.03 units on a scale STANDARD_DEVIATION 1.08 |
| Region of Enrollment United States | 17 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Brain Regional Gray Matter Density
Gray matter density (GMD) of the prefrontal cortex region identified as placebo biomarker. Placebo responders/non-responders were identified based on the VAS score. A minimum of 20% decrease in VAS score was needed to be qualified as responders. GMD is a value between 0 and 1 representing the intensity of every brain voxels. The GMD of the prefrontal cortex region represent the average GMD of every voxels in this region.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Responders | Brain Regional Gray Matter Density | 0.420 Gray Matter Density: 0 to 1 | Standard Deviation 0.083 |
| Placebo Non-responders | Brain Regional Gray Matter Density | 0.425 Gray Matter Density: 0 to 1 | Standard Deviation 0.06 |
Secondary
Overall Brain Neocortical Gray Matter Volume
Time frame: 2 weeks
Population: Data were not collected and the Outcome will never be analyzed
Secondary
WOMAC Pain Index
Osteoarthritis (OA) specific pain and quality of life index (the Western Ontario and McMaster Universities Osteoarthritis Index WOMAC). The WOMAC score is from 0 to 96 where 0 represent no pain and quality of life impairment due to OA and 96 represent the worst pain and quality of life impairment due to OA. The outcome is reported as the percent change from baseline to end of treatment (2 weeks).
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Responders | WOMAC Pain Index | 38.6 Percent Change in WOMAC score | Standard Deviation 24.6 |
| Placebo Non-responders | WOMAC Pain Index | 4.6 Percent Change in WOMAC score | Standard Deviation 21.3 |