Bone Marrow Aspirate Concentrate Versus Triamcinolone Injection For Hip Osteoarthritis

Study Overview
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Brief Summary
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This is a single site, randomized single blinded, two arm study researching the effects of bone marrow aspirate concentrate (BMAC) versus Triamcinolone in patients with hip osteoarthritis. The aims and hypothesis are as follows: Specific Aim 1: Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 12 months (6 weeks, 3 months, 6 months, and 12 months). Hypothesis: The investigators hypothesize that triamcinolone and BMAC groups will have pain reduction after each respective intervention. The changes with triamcinolone will be noticeable on the short term. The BMAC changes will take longer to have an effect but will longer duration. The investigators hypothesize that at 6 months and 1 year participants receiving BMAC will have better scores reported on the WOMAC compared to the triamcinolone injection and better than prior to injection. Specific Aim 2: Evaluate the change of bone marrow aspirate injection in comparison to triamcinolone in participant's performance on the 6 minute walk test from baseline to 12 months (6 weeks, 3 months, 6 months, and 12 months). Hypothesis: The investigators hypothesize that there will be higher walking distances on the 6 minute walk test in the participants receiving a BMAC injection in comparison to triamcinolone starting at the 3 months follow-up time. Specific Aim 3: Quantify and correlate cell characterization with patient reported outcomes score. Hypothesis: The investigators hypothesize that there will be better patient reported outcomes in patients who have a higher concentration of mesenchymal stem cells injected. The investigators will enroll 50 patients into each arm. Bone marrow will be aspirated then subsequently concentrated using the Emcyte PureBMC kit. The investigators will test the BMAC viability, rapid sterility, endotoxin, platelet concentration, volume, and total nucleated cell counts prior to injecting. The BMAC will be utilized as a hip injection into the affected hip of the patient. Patients receiving the Triamcinolone will undergo a sham bone needling to simulate the aspiration to keep patients blinded. Both groups will receive their injections under ultrasound guidance.

Detailed Description
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The goal of the study is to enroll 50 subjects in the bone marrow arm (BMAC group) and 50 in the triamcinolone arm (triamcinolone group). Once part fulfill the inclusion criteria, participants will be randomized to either intervention. Participants will be enrolled in a staggering manner for the BMAC arm. The first 4 participants will be enrolled with at least 1 week interval in between these patients. During these weeks, the investigators will obtain results from the BMAC culture and evaluate safety response to the procedure. Participants enrolled in the triamcinolone arm will not be enrolled in a staggering manner, as the safety and efficacy are established as this is part of standard of care for hip osteoarthritis. Participants will have the study protocol explained to them and will consent to the study, agreeing to have the bone marrow aspiration (BMA) and hip injection performed. Prior to any interventions, the participants will complete the baseline patient reported outcomes scores, and blood draw outlined in SOA section 1.3 Inclusion and exclusion criteria will be assessed during screening. Kellgren-Lawrence grade will be determined by blinded radiologists and co-investigators (Drs. Amer Hanano and Carl Winalski). An average score will be taken. In order to blind the patient of the intervention, the triamcinolone group will undergo a sham bone needling of the bone cortex to simulate bone marrow harvesting (BMH). The posterior iliac spine will be anesthetized and needled simulating a BMH. Following the needling, the group will then receive a triamcinolone injection. The process of aspirating the bone marrow used has been described by Dr. Friedlis and Dr. Centeno and will be completed under ultrasound guidance and in sterile fashion19. Multiple small draws of maximum 10 cc will be completed from different locations in the posterior superior iliac spine. The procedure as described is safe and been completed in more than 2000 individuals. Three to six passes are completed on each posterior superior iliac spine and a total volume of 60 cc of bone marrow is aspirated. The BMAC group will have bone marrow aspirated using the Emcyte ASPIRE™ needle and subsequently concentrated using the Emcyte PureBMC™ system. 1 cc will be sent for further testing at Biosciences Research Associates and 1 cc will be utilized for endotoxin testing, total nucleated cell counts (TNC), gram stain, and viability. BMAC concentration including TNC will be analyzed on a hematology analyzer, Micros ES 60, immediately after the device concentrates the bone marrow. The parameters are set below: Parameter Acceptance criteria Total Nucleated cell count (TNC) ≥40 x 106 cells/mL Platelet Concentration ≥ 600 x 106 cells/mL Final volume (from the device) ≥ 7 mL The investigators will measure endotoxin concentrations utilizing the Charles River Nexgen PTS point of care instrument. The limit of endotoxin for general medical devices is 0.5 EU/device output. The investigators will abide by this parameter. All testing will be performed immediately after the device concentrates the bone marrow and before injection into patient to ensure the device output safety. Rapid sterility will be assessed using a gram stain, performed by a CLIA certified laboratory at Cleveland Clinic Florida. If gram stain is positive, the aspirate will not be injected. Patient will be considered a screen failure. All testing will be performed immediately after the device concentrates the bone marrow and before injection into patient to ensure the device output safety. Viability will be measured at bedside, as well as at Biosciences Research Associates. Cells will be stained with trypan blue and subsequently read on an autofocus, automated cell counter. Viability of 90% or more is expected. All testing will be performed immediately after the device concentrates the bone marrow and before injection into patient to ensure the device output safety. Rapid sterility testing will be completed at Cleveland Clinic Florida CAP accredited lab and 14 day sterility will be further analyzed by independent Wuxi AppTec. The remaining 5 cc will be utilized as the intervention group injectate. The BMAC will be injected as is and will not undergo any further manipulation and/or dilution. The 5 cc BMAC dose or triamcinolone will be injected into a single affected hip joint under ultrasound guidance. Once the injection has been completed, patient will be monitored for 15 minutes and discharged home. Participants will be instructed to not use ice or anti-inflammatory medications for at least 6 weeks. For pain control following the procedure, the participant will be recommended to use acetaminophen or tramadol depending on the severity. Heat may be applied to the hip joint in case of muscle tightness. Ice should be avoided at the injection site. It may be applied at the site of bone marrow aspiration. Participant will then follow-up in 6 weeks, 3 months, 6 months, and 1 year post-procedure to completed PROs and functional assessment with research staff. Participants will be asked to communicate to the Principal Investigator when anti-inflammatory medications are initiated, if necessary. Following the injections, both groups will resume home exercise program which participants had been completing prior to the injection in a pain free approach.

Official Title
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Randomized Trial on the Evaluation of the Effectiveness of One Single Bone Marrow Aspirate Hip Injection Versus Triamcinolone for Hip Osteoarthritis

Conditions
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Hip Osteoarthritis

Intervention / Treatment
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* Combination Product: Aspire Needle + Emcyte PureBMC
* Drug: Triamcinolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged between 18 - 65 years old WOMAC ≥ 50 Kellgren-Lawrence Grade 2 or higher on Hip X-Rays Body Mass Index < 35 kg/m2 Unilateral or Bilateral Hip Osteoarthritis Prior physical therapy treatment for 6 weeks in the last 6 months Agreement to adhere to Lifestyle Considerations (see section 5.3) At least 60 cc of BMAC acquired during aspiration/concentration process Discontinuation of pain/anti-inflammatory medications 2 week prior to baseline measurements Patients with cancer in remission for at least 5 years Total Nucleated cell count (TNC) ≥ 40 x 106 cells/mL Platelet Concentration ≥ 600 x 106 cells/mL Endotoxin < 0.5 EU/device output Viability ≥ 90% Negative gram stain result Exclusion Criteria: Prior corticosteroid injection to the hip History of hip replacement(s) Noncompliance to prevent screening tests for cancer indicated by age Active autoimmune disease Current use of oral corticosteroid Inability to be weaned of oral anti-inflammatory medications History of Diabetes or HbA1c > 6.5% Uncontrolled Thyroid Dysfunction: 0.450 uIU/mL ≥ TSH levels ≥ 4.500 uIU/mL Vitamin D Level < 30 ng/ml Anemia (Hgb < 12 g/dL for Women; Hgb < 13 g/dL for men) eGFR < 60 mL/min/1.73 m^2 Thrombocytopenia with platelet count less than 150,000 x 109 L Patients with coagulopathies based on known clotting disorder Patients currently on anti-coagulation therapies Patients who report any active infection(s) including cellulitis, TB, HIV, COVID, Hepatitis B and C Moving over the next year Inability to consent to the research study Inability to complete forms electronically Subjects in any other clinical trials History of allergic reaction to lidocaine Pregnancy and/or planning to become pregnant during trial Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: bone marrow aspirate concentrate versus triamcinolone
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bone marrow aspirate concentrate<br>Bone marrow that is aspirated then concentrated using a device. | Combination Product: Aspire Needle + Emcyte PureBMC<br>* The Aspire Needle will be utilized to extract the bone marrow and the Emcyte PureBMC will be used to concentrate bone marrow aspirate. The final concentrate will be injected into the hip.<br>|
| Active Comparator: Triamcinolone<br>Triamcinolone is a corticosteroid. | Drug: Triamcinolone<br>* 40 mg (1 mL) triamcinolone and 4 cc of lidocaine 1% that will be injected into the hip.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario McMaster Universities Arthritis Index (WOMAC) | WOMAC Scores range from 0 to 96, with higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 6 weeks. | 
| Western Ontario McMaster Universities Arthritis Index (WOMAC) | WOMAC Scores range from 0 to 96, with higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 3 months. | 
| Western Ontario McMaster Universities Arthritis Index (WOMAC) | WOMAC Scores range from 0 to 96, with higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 6 months. | 
| Western Ontario McMaster Universities Arthritis Index (WOMAC) | WOMAC Scores range from 0 to 96, with higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Test (6MWT) | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. This outcome is used to measure the farthest distance walked within 6 minutes. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 6 weeks. | 
| 6 Minute Walk Test (6MWT) | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. This outcome is used to measure the farthest distance walked within 6 minutes. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 3 months. | 
| 6 Minute Walk Test (6MWT) | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. This outcome is used to measure the farthest distance walked within 6 minutes. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 6 months. | 
| 6 Minute Walk Test (6MWT) | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. This outcome is used to measure the farthest distance walked within 6 minutes. | Evaluate the change in pain and functional scores of a single bone marrow aspirate injection in comparison to triamcinolone in patients with hip osteoarthritis through validated patient reported outcomes scores at baseline to 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone marrow aspirate concentrate, triamcinolone