Osteoarthritis, Osteo Arthritis Knee
Conditions
Brief summary
This prospective, double-blinded, placebo-controlled, randomized trial will enroll 120 SKOA subjects at the NYU Center for Musculoskeletal Care. Patients meeting entry criteria will be randomized 1:1 to treatment with colchicine or placebo daily for 3 months. Subjects will have detailed evaluation of standardized clinical pain outcomes, candidate peripheral blood biomarkers, baseline knee radiographs as well as MSK-US, and a subset will undergo evaluation of their synovial fluid.
Interventions
DRUGColchicine 0.8 mg or 0.6 mg orally once daily
Colchicine 0.8 mg orally once daily for 1.5 months, and then 0.6 mg once daily for the remainder of the time (1.5 months)
DRUGPlacebo oral capsule
Placebo 0.8 mg or 0.6 mg orally once daily for 3 months
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Are 40 years old or older * Continue to experience frequent knee symptoms as defined above * Have KL grade 2 or 3 on their last knee radiograph done for the parent study * Have an estimated glomerular filtration rate (eGFR) \> 30 ml/min (MDRD equation) and liver transaminases \< 2x the upper limit of normal * Have a BMI ≤ 32 at the time of enrollment * Agree to be randomized to take colchicine or placebo daily for 3 months
Exclusion criteria
* Have received hyaluronic acid or corticosteroid steroid injection within the past 3 months * Have a diagnosis of gout/pseudogout or other inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy etc). * Have a diagnosis of diabetes mellitus, chronic infectious disease, congestive heart failure, non-cutaneous cancer within the past 5 years * Plan on undergoing total knee replacement within the next 3 months * Be using any medication that is a strong CYP3A4 inhibitor whose metabolism may interact with colchicine (e.g., certain protease inhibitors, certain azole antifungal agents, clarithromycin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale (VAS) Pain Score | Baseline, 3 Months | VAS is a tool widely used to measure pain. A patient is asked to indicate his/her perceived pain intensity (most commonly) along a 10 mm horizontal line, and this rating is then measured from the left edge (=VAS score). The total score range is 0 (no pain) to 10 (worst pain imaginable); the higher the score, the worse the pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the KOOS Stiffness Score | Baseline, 3 Months | The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). Each item on the KOOS is scored on a scale from 0 (no problems) to 4 (extreme problems), and then the scores are calculated to generate a final score between 0 and 100. The KOOS stiffness score is a percentage from 0 to 100 that measures how much stiffness a patient experiences in their knee. A score of 0 indicates the most stiffness, while a score of 100 indicates no stiffness. |
| Change in the KOOS Physical Function Score | Baseline, 3 Months | The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Physical Function items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems. The scores for each dimension are then transformed to a scale from 0 to 100, where 0 represents extreme problems with knee function and 100 indicates no problems at all. |
| Change in the KOOS Quality of Life Score | Baseline, 3 Months | The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). A KOOS Quality of Life score ranges from 0 to 100, where 0 represents the worst possible knee-related quality of life and 100 indicates no problems at all. A higher score indicates better quality of life related to the knee. |
| Change in the KOOS Sports and Recreational Activities | Baseline, 3 Months | The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Sports and Recreational Activities 9 items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems relating to sports and recreational activities. The scores are then transformed to a scale from 0 to 100, with 100 indicating no knee problems with sports and recreational activities and 0 indicating extreme knee problems with sports and recreational activities . |
| Change in the KOOS Total Score | Baseline, 3 Months | The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The total range for each sub-category is 0-100, making the total range for the whole survey 0-500. The higher the score, the worse the symptoms and pain/ higher difficulty in function. |
| Number of Participants Who Used Acetaminophen or Other Medications for Pain | 6 weeks | — |
| Change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Score | Baseline, 3 Months | The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The KOOS Pain Score refers to a specific subscale within the KOOS questionnaire that measures the severity of knee pain experienced by a patient, consisting of nine questions where each response is scored on a scale from 0 (no pain) to 4 (extreme pain), with a higher score indicating greater pain intensity; the overall pain score is then calculated as a percentage of the maximum possible score, where 0 represents the worst possible pain and 100 represents no pain at all. |
| Change in Inflammatory Plasma Marker: Interleukin-1 Receptor Antagonist (IL-1Ra) | Baseline, 3 months | — |
| Change in Inflammatory Plasma Marker: Prostaglandin E2 (PGE2) | Baseline, 3 months | — |
| Change in Musculoskeletal Ultrasound (MSK-US)-Measured Effusion | Baseline, 3 months | Size of effusion is measured as millimeters |
| Change in Rates of Crystal Deposition (Urate, Calcium) on MSK-US | Baseline, 3 months | — |
| Change in Inflammatory Plasma Marker: Highly Sensitive C-reactive Protein (hsCRP) | Baseline, 3 months | — |
| Change in Inflammatory Plasma Marker: Uric Acid | Baseline, 3 months | — |
| Change in Number of Participants Who Used Acetaminophen or Other Medications for Pain | 6 weeks, 3 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo in capsule identical to study drug
Placebo oral capsule: Placebo 0.8 mg or 0.6 mg orally once daily for 3 months | 51 |
| Colchicine 0.6 or 0.8 mg orally once daily.
Because recent studies suggest that a dose of 0.6mg may be sufficient for chronic inflammatory suppression and may reduce the already low risk of toxicity of 0.8mg, for the remainder (second half) of the study the dosage will be switched from 0.8mg to a 0.6mg dose to allow comparison of the two doses.
Colchicine 0.8 mg or 0.6 mg orally once daily: Colchicine 0.8 mg orally once daily for 1.5 months, and then 0.6 mg once daily for the remainder of the time (1.5 months) | 49 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Terminations | 2 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | Colchicine |
|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 10.3 | 66.5 years STANDARD_DEVIATION 10.2 | 66.1 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 22 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 78 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 25 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) White | 33 Participants | 63 Participants | 30 Participants |
| Region of Enrollment United States | 51 participants | 100 participants | 49 participants |
| Sex: Female, Male Female | 33 Participants | 68 Participants | 35 Participants |
| Sex: Female, Male Male | 18 Participants | 32 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 49 |
| other Total, other adverse events | 34 / 51 | 36 / 49 |
| serious Total, serious adverse events | 0 / 51 | 0 / 49 |
Outcome results
Primary
Change in Visual Analog Scale (VAS) Pain Score
VAS is a tool widely used to measure pain. A patient is asked to indicate his/her perceived pain intensity (most commonly) along a 10 mm horizontal line, and this rating is then measured from the left edge (=VAS score). The total score range is 0 (no pain) to 10 (worst pain imaginable); the higher the score, the worse the pain.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Visual Analog Scale (VAS) Pain Score | -1.45 score on a scale | Standard Deviation 2.45 |
| Colchicine | Change in Visual Analog Scale (VAS) Pain Score | -1.16 score on a scale | Standard Deviation 2.22 |
Secondary
Change in Inflammatory Plasma Marker: Highly Sensitive C-reactive Protein (hsCRP)
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Inflammatory Plasma Marker: Highly Sensitive C-reactive Protein (hsCRP) | 0.1 mg/L | Standard Deviation 4.1 |
| Colchicine | Change in Inflammatory Plasma Marker: Highly Sensitive C-reactive Protein (hsCRP) | -4.7 mg/L | Standard Deviation 15.6 |
Secondary
Change in Inflammatory Plasma Marker: Interleukin-1 Receptor Antagonist (IL-1Ra)
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Inflammatory Plasma Marker: Interleukin-1 Receptor Antagonist (IL-1Ra) | -66 pg/mL | Standard Deviation 231.9 |
| Colchicine | Change in Inflammatory Plasma Marker: Interleukin-1 Receptor Antagonist (IL-1Ra) | -7.3 pg/mL | Standard Deviation 194 |
Secondary
Change in Inflammatory Plasma Marker: Prostaglandin E2 (PGE2)
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Inflammatory Plasma Marker: Prostaglandin E2 (PGE2) | 100 pg/mL | Standard Deviation 586.4 |
| Colchicine | Change in Inflammatory Plasma Marker: Prostaglandin E2 (PGE2) | 72.4 pg/mL | Standard Deviation 737.3 |
Secondary
Change in Inflammatory Plasma Marker: Uric Acid
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Inflammatory Plasma Marker: Uric Acid | 0.2 mg/dL | Standard Deviation 0.7 |
| Colchicine | Change in Inflammatory Plasma Marker: Uric Acid | -0.8 mg/dL | Standard Deviation 1 |
Secondary
Change in Musculoskeletal Ultrasound (MSK-US)-Measured Effusion
Size of effusion is measured as millimeters
Time frame: Baseline, 3 months
Population: In lieu of synovitis whose measurements proved difficult, the team relied on MSK-US-measured effusions. Only 28 and 19 participants effusion data were collected for the placebo and colchicine group, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Musculoskeletal Ultrasound (MSK-US)-Measured Effusion | -1.2 millimeter | Standard Deviation 2.4 |
| Colchicine | Change in Musculoskeletal Ultrasound (MSK-US)-Measured Effusion | -1.5 millimeter | Standard Deviation 3 |
Secondary
Change in Number of Participants Who Used Acetaminophen or Other Medications for Pain
Time frame: 6 weeks, 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Change in Number of Participants Who Used Acetaminophen or Other Medications for Pain | -1 participants |
| Colchicine | Change in Number of Participants Who Used Acetaminophen or Other Medications for Pain | 1 participants |
Secondary
Change in Rates of Crystal Deposition (Urate, Calcium) on MSK-US
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Rates of Crystal Deposition (Urate, Calcium) on MSK-US | 0 mg/dL | Standard Deviation 0 |
| Colchicine | Change in Rates of Crystal Deposition (Urate, Calcium) on MSK-US | 0 mg/dL | Standard Deviation 0 |
Secondary
Change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Score
The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The KOOS Pain Score refers to a specific subscale within the KOOS questionnaire that measures the severity of knee pain experienced by a patient, consisting of nine questions where each response is scored on a scale from 0 (no pain) to 4 (extreme pain), with a higher score indicating greater pain intensity; the overall pain score is then calculated as a percentage of the maximum possible score, where 0 represents the worst possible pain and 100 represents no pain at all.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Score | 9.5 score on a scale | Standard Deviation 20 |
| Colchicine | Change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Score | 5.2 score on a scale | Standard Deviation 19 |
Secondary
Change in the KOOS Physical Function Score
The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Physical Function items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems. The scores for each dimension are then transformed to a scale from 0 to 100, where 0 represents extreme problems with knee function and 100 indicates no problems at all.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the KOOS Physical Function Score | 9.8 score on a scale | Standard Deviation 17.6 |
| Colchicine | Change in the KOOS Physical Function Score | 7.4 score on a scale | Standard Deviation 17.5 |
Secondary
Change in the KOOS Quality of Life Score
The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). A KOOS Quality of Life score ranges from 0 to 100, where 0 represents the worst possible knee-related quality of life and 100 indicates no problems at all. A higher score indicates better quality of life related to the knee.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the KOOS Quality of Life Score | 6.9 score on a scale | Standard Deviation 22 |
| Colchicine | Change in the KOOS Quality of Life Score | 3.5 score on a scale | Standard Deviation 15.8 |
Secondary
Change in the KOOS Sports and Recreational Activities
The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Sports and Recreational Activities 9 items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems relating to sports and recreational activities. The scores are then transformed to a scale from 0 to 100, with 100 indicating no knee problems with sports and recreational activities and 0 indicating extreme knee problems with sports and recreational activities .
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the KOOS Sports and Recreational Activities | 0.0 score on a scale | Standard Deviation 25.8 |
| Colchicine | Change in the KOOS Sports and Recreational Activities | 2.8 score on a scale | Standard Deviation 19.4 |
Secondary
Change in the KOOS Stiffness Score
The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). Each item on the KOOS is scored on a scale from 0 (no problems) to 4 (extreme problems), and then the scores are calculated to generate a final score between 0 and 100. The KOOS stiffness score is a percentage from 0 to 100 that measures how much stiffness a patient experiences in their knee. A score of 0 indicates the most stiffness, while a score of 100 indicates no stiffness.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the KOOS Stiffness Score | 6.6 score on a scale | Standard Deviation 15.7 |
| Colchicine | Change in the KOOS Stiffness Score | 5.5 score on a scale | Standard Deviation 19.1 |
Secondary
Change in the KOOS Total Score
The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The total range for each sub-category is 0-100, making the total range for the whole survey 0-500. The higher the score, the worse the symptoms and pain/ higher difficulty in function.
Time frame: Baseline, 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the KOOS Total Score | 6.5 score on a scale | Standard Deviation 20.7 |
| Colchicine | Change in the KOOS Total Score | 4.9 score on a scale | Standard Deviation 18.1 |
Secondary
Number of Participants Who Used Acetaminophen or Other Medications for Pain
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Used Acetaminophen or Other Medications for Pain | 16 Participants |
| Colchicine | Number of Participants Who Used Acetaminophen or Other Medications for Pain | 12 Participants |
Secondary
Number of Participants Who Used Acetaminophen or Other Medications for Pain
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Used Acetaminophen or Other Medications for Pain | 15 Participants |
| Colchicine | Number of Participants Who Used Acetaminophen or Other Medications for Pain | 13 Participants |