Knee Osteoarthritis
Conditions
Keywords
knee osteoarthritis, regenerative medicine, orthobiologics, cellular therapy
Brief summary
The purpose of this study is to determine the clinical response to autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) injections for knee osteoarthritis with respect to pain, function, and quality of life at up to 1 year following the intervention. Specifically, the clinical response will be compared to baseline and a control group treated with a Gel-One® hyaluronate injection to the target knee.
Interventions
BIOLOGICALBMAC injection
60mL of bone marrow will be collected from a bone near the hip. Approximately 5-6mL of the bone marrow aspirate concentrate is then used for injection, under ultrasound guidance, into the target knee by the study physician.
BIOLOGICALPRP injection
60mL of venous blood will be withdrawn from either arm. Approximately 4-5 ml of platelet-rich plasma will be introduced under ultrasound guidance to the subject's target knee by the study physician.
DEVICEGel-One® hyaluronate injection
Patients will receive a single injection of Gel-One® (3 ml syringe of Gel-One® - 1% solution \[10 mg/mL\], 30mg total hyaluronan) into the target knee. Injections will be performed by the study physician under real-time dynamic ultrasound guidance.
Sponsors
OhioHealth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients 40 to 70 years old 2. Diagnosed with knee osteoarthritis based on the American College of Rheumatology criteria including symptomatic reports and radiographic findings 3. Kellgren-Lawrence grade 1-3 based on a radiograph within 6 months of presentation to the clinic 4. Symptomatic evidence of tibiofemoral osteoarthritis for ≥6 months 5. Average numeric pain rating of 4 - 8 on a scale of zero to 10 (defined as moderate level) over the past week 6. Previous trial of 6 weeks minimum of conservative therapy including physical therapy, weight loss, anti-inflammatory medication, or injection therapy
Exclusion criteria
1. Grade 4 knee osteoarthritis according to the Kellgren-Lawrence scale 2. History of intraarticular viscosupplementation or steroid injection in the target knee in the past 6 months at the time of the baseline visit or intraarticular injection planned during the trial 3. History of arthroscopic surgery in the target knee in the past 12 months at the time of presentation to the clinic or planned surgery during the trial period (e.g., scheduled for/awaiting arthroscopy or a knee replacement procedure) 4. Bilateral knee osteoarthritis (unless the contralateral knee involvement is limited to radiographic osteoarthritis and not symptomatic) 5. Ipsilateral (same side) or contralateral (opposite side) symptomatic osteoarthritis of hip or ankle 6. Clinically apparent tense effusion or other acute inflammation of the target knee at the time of presentation to the clinic 7. Active infection of either lower extremity such as cellulitis or any skin disease or infection in the area where BMAC is aspirated, blood is drawn, or an injection is given 8. History of diagnosis of any of the following: 1) septic osteoarthritis of any joint, 2) inflammatory arthropathy such as rheumatoid arthritis, gout, pseudogout, lupus, crystalline arthropathy, chondrocalcinosis and other rheumatology diagnoses 9. Cruciate/collateral knee ligament instability, ligament laxity, or meniscal instability of the target knee 10. Significant alignment deformity such as varus/valgus of the target knee in the judgment of the investigator 11. Currently pregnant, nursing, or planning to become pregnant during the trial period 12. Previous or known allergic reaction or hypersensitivity to heparin; sodium citrate; hyaluronan products or specifically Gel-One®; cinnamon; bird products such as feathers, eggs, or poultry; avian proteins 13. Not suitable for BMAC tissue allograft injection per physician (e.g., blood dyscrasia) 14. Unable to be prescribed stable dose of NSAIDs and/or tramadol based on medical history as ad lib use of over-the-counter analgesics will be allowed in both groups after treatment 15. Current cigarette smoker 16. Unable to give informed consent 17. Non-English speaking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Knee Injury and Osteoarthritis Outcome Score | Change from baseline to 3, 6, and 12 months post-treatment | Subscales include pain, symptoms, function in activities of daily living, function in sport and recreation, and knee-related quality of life. Each subscale is 0-100 with 100 indicating the best possible score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Pain Rating Scale | Change from baseline to 3, 6, and 12 months post-treatment | Scale from 0-10 with 0 representing no pain and 10 representing worst imaginable pain |
| Patient Reported Outcome Measurement Information System Global Health Scores | Change from baseline to 3, 6, and 12 months post-treatment | The Patient Reported Outcomes Measurement Information System (PROMIS®) Global Health scale v1.1 contains 10 questions and produces two subscale scores: Global Physical Health (GPH) and Global Mental Health (GMH) (Hays, Bjorner, Revicki, Spritzer, & Cella, 2009). Each subscale produces a raw score that is converted to a T score such that an average patient in the United States would have a subscale T score of 50 with a standard deviation of 10 points (Global Health: A Brief Guide to the PROMIS® Global Health Instruments, 2017). A score higher than the mean indicates a more desirable score, and vice versa. A positive change score indicates an improvement, while a negative change score indicates a decline in score value. |
Countries
United States
Participant flow
Recruitment details
Number of participants to be treated was capped at 30 participants. However, the approved protocol allowed enrollment of up to 45 participants to achieve a treatment group of 30 participants.
Pre-assignment details
Based on the recruitment details stated, if a participant enrolled but subsequently withdrew or was withdrawn prior to treatment, another participant was enrolled in order to achieve a number of 30 participants who were treated within the study. Per protocol, consented patients could include up to 45 if needed to achieve 30 treated participants.
Participants by arm
| Arm | Count |
|---|---|
| BMAC Injection and PRP Injection Injection of bone marrow aspirate concentrate (BMAC) withdrawn from a bone near the hip into the knee joint (intra-articular) immediately followed by an injection of platelet-rich plasma (PRP) into the knee joint.
BMAC injection: 60mL of bone marrow will be collected from a bone near the hip. Approximately 5-6mL of the bone marrow aspirate concentrate is then used for injection, under ultrasound guidance, into the target knee by the study physician.
PRP injection: 60mL of venous blood will be withdrawn from either arm. Approximately 4-5 ml of platelet-rich plasma will be introduced under ultrasound guidance to the subject's target knee by the study physician. | 17 |
| Gel-One® Hyaluronate Injection Gel-One® is an hyaluronate gel used in the treatment of knee osteoarthritis by injection into the knee joint (intra-articular).
Gel-One® hyaluronate injection: Patients will receive a single injection of Gel-One® (3 ml syringe of Gel-One® - 1% solution \[10 mg/mL\], 30mg total hyaluronan) into the target knee. Injections will be performed by the study physician under real-time dynamic ultrasound guidance. | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Enrollment to Actual Treatment Complete | Physician Decision | 1 | 0 |
| Enrollment to Actual Treatment Complete | Withdrawal by Subject | 1 | 0 |
| Follow-up Visits | Additional treatment pursued | 2 | 1 |
Baseline characteristics
| Characteristic | Gel-One® Hyaluronate Injection | Total | BMAC Injection and PRP Injection |
|---|---|---|---|
| Age, Continuous | 58.60 years STANDARD_DEVIATION 8.05 | 58.31 years STANDARD_DEVIATION 8.51 | 58.06 years STANDARD_DEVIATION 9.14 |
| BMI | 29.21 kg/m^2 STANDARD_DEVIATION 7.05 | 29.20 kg/m^2 STANDARD_DEVIATION 6.03 | 29.19 kg/m^2 STANDARD_DEVIATION 5.19 |
| Kellgren-Lawrence grade (n, %) Grade 1 | 2 Participants | 7 Participants | 5 Participants |
| Kellgren-Lawrence grade (n, %) Grade 2 | 8 Participants | 14 Participants | 6 Participants |
| Kellgren-Lawrence grade (n, %) Grade 3 | 5 Participants | 11 Participants | 6 Participants |
| KOOS ADLs | 70.13 units on a scale STANDARD_DEVIATION 18.34 | 69.31 units on a scale STANDARD_DEVIATION 17.87 | 68.59 units on a scale STANDARD_DEVIATION 17.98 |
| KOOS Pain | 63.33 units on a scale STANDARD_DEVIATION 17.72 | 62.00 units on a scale STANDARD_DEVIATION 16.13 | 60.82 units on a scale STANDARD_DEVIATION 15.05 |
| KOOS Quality of Life | 38.47 units on a scale STANDARD_DEVIATION 15.94 | 37.25 units on a scale STANDARD_DEVIATION 17.11 | 36.18 units on a scale STANDARD_DEVIATION 18.5 |
| KOOS Sport & Recreation | 39.67 units on a scale STANDARD_DEVIATION 21.59 | 35.31 units on a scale STANDARD_DEVIATION 22.68 | 31.47 units on a scale STANDARD_DEVIATION 23.57 |
| KOOS Symptoms | 68.80 units on a scale STANDARD_DEVIATION 15.69 | 67.59 units on a scale STANDARD_DEVIATION 15.65 | 66.54 units on a scale STANDARD_DEVIATION 16.01 |
| NPRS | 4.20 units on a scale STANDARD_DEVIATION 1.7 | 4.41 units on a scale STANDARD_DEVIATION 1.76 | 4.59 units on a scale STANDARD_DEVIATION 1.84 |
| Onset/course of target knee Insidious | 9 Participants | 21 Participants | 12 Participants |
| Onset/course of target knee Traumatic | 6 Participants | 11 Participants | 5 Participants |
| Previous injection on target knee No | 8 Participants | 14 Participants | 6 Participants |
| Previous injection on target knee Yes | 7 Participants | 18 Participants | 11 Participants |
| Previous physical therapy on target knee No | 9 Participants | 13 Participants | 4 Participants |
| Previous physical therapy on target knee Yes | 6 Participants | 19 Participants | 13 Participants |
| Previous surgery on target knee knee No | 6 Participants | 13 Participants | 7 Participants |
| Previous surgery on target knee knee Yes | 9 Participants | 19 Participants | 10 Participants |
| PROMIS Global Health Mental Score | 51.90 units on a scale STANDARD_DEVIATION 9.36 | 51.89 units on a scale STANDARD_DEVIATION 7.25 | 51.88 units on a scale STANDARD_DEVIATION 5.02 |
| PROMIS Global Health Physical Score | 48.23 units on a scale STANDARD_DEVIATION 7.99 | 46.31 units on a scale STANDARD_DEVIATION 7.88 | 44.62 units on a scale STANDARD_DEVIATION 7.61 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 1 / 17 | 0 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
Knee Injury and Osteoarthritis Outcome Score
Subscales include pain, symptoms, function in activities of daily living, function in sport and recreation, and knee-related quality of life. Each subscale is 0-100 with 100 indicating the best possible score.
Time frame: Change from baseline to 3, 6, and 12 months post-treatment
Population: One participant in the BMAC injection and PRP injection group withdrew prior to the 6 month follow-up and another prior to the 12 month follow-up both due to the pursuit of an additional treatment option. One participant in the hyaluronate injection group withdrew prior to the 6 month follow-up due to pursuit of an additional treatment option.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (3 months) | 21.02 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (6 months) | 34.89 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (3 months) | 14.00 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (6 months) | 24.97 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (6 months) | 20.03 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (12 months) | 23.48 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (3 months) | 29.46 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (12 months) | 18.01 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (6 months) | 14.26 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADLs (12 months) | 19.10 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADL (3 months) | 15.35 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (12 months) | 39.07 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADLs (6 months) | 18.13 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (12 months) | 27.44 score on a scale |
| BMAC Injection and PRP Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (3 months) | 16.71 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (12 months) | 21.46 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (3 months) | 10.93 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (3 months) | 10.47 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADL (3 months) | 12.47 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (3 months) | 30.07 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (3 months) | 21.27 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (6 months) | 12.52 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (6 months) | 12.41 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADLs (6 months) | 14.94 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (6 months) | 31.62 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS QOL (6 months) | 24.18 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Pain (12 months) | 12.67 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Symptoms (12 months) | 8.20 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS ADLs (12 months) | 11.87 score on a scale |
| Gel-One® Hyaluronate Injection | Knee Injury and Osteoarthritis Outcome Score | KOOS Sport (12 months) | 26.05 score on a scale |
Secondary
Numeric Pain Rating Scale
Scale from 0-10 with 0 representing no pain and 10 representing worst imaginable pain
Time frame: Change from baseline to 3, 6, and 12 months post-treatment
Population: One participant in the BMAC injection and PRP injection group withdrew prior to the 6 month follow-up and another prior to the 12 month follow-up both due to the pursuit of an additional treatment option. One participant in the hyaluronate injection group withdrew prior to the 6 month follow-up due to pursuit of an additional treatment option.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BMAC Injection and PRP Injection | Numeric Pain Rating Scale | NPRS (3 months) | -1.92 score on a scale |
| BMAC Injection and PRP Injection | Numeric Pain Rating Scale | NPRS (6 months) | -2.45 score on a scale |
| BMAC Injection and PRP Injection | Numeric Pain Rating Scale | NPRS (12 months) | -3.13 score on a scale |
| Gel-One® Hyaluronate Injection | Numeric Pain Rating Scale | NPRS (3 months) | -1.87 score on a scale |
| Gel-One® Hyaluronate Injection | Numeric Pain Rating Scale | NPRS (6 months) | -1.77 score on a scale |
| Gel-One® Hyaluronate Injection | Numeric Pain Rating Scale | NPRS (12 months) | -1.56 score on a scale |
Secondary
Patient Reported Outcome Measurement Information System Global Health Scores
The Patient Reported Outcomes Measurement Information System (PROMIS®) Global Health scale v1.1 contains 10 questions and produces two subscale scores: Global Physical Health (GPH) and Global Mental Health (GMH) (Hays, Bjorner, Revicki, Spritzer, & Cella, 2009). Each subscale produces a raw score that is converted to a T score such that an average patient in the United States would have a subscale T score of 50 with a standard deviation of 10 points (Global Health: A Brief Guide to the PROMIS® Global Health Instruments, 2017). A score higher than the mean indicates a more desirable score, and vice versa. A positive change score indicates an improvement, while a negative change score indicates a decline in score value.
Time frame: Change from baseline to 3, 6, and 12 months post-treatment
Population: One participant in the BMAC injection and PRP injection group withdrew prior to the 6 month follow-up and another prior to the 12 month follow-up both due to the pursuit of an additional treatment option. One participant in the hyaluronate injection group withdrew prior to the 6 month follow-up due to pursuit of an additional treatment option.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (3 months) | 4.62 score on a scale |
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (3 months) | -2.18 score on a scale |
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (6 months) | 6.76 score on a scale |
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (6 months) | -0.01 score on a scale |
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (12 months) | 4.77 score on a scale |
| BMAC Injection and PRP Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (12 months) | 0.07 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (12 months) | 3.26 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (3 months) | 0.59 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (6 months) | 2.24 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (3 months) | -0.65 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Mental Health (12 months) | 3.01 score on a scale |
| Gel-One® Hyaluronate Injection | Patient Reported Outcome Measurement Information System Global Health Scores | PROMIS Physical Health (6 months) | 3.50 score on a scale |