Clinical trial NCT04990128: Bone Marrow Aspirate Concentrate Versus Triamcinolone Injection For Hip Osteoarthritis
Official title: Randomized Trial on the Evaluation of the Effectiveness of One Single Bone Marrow Aspirate Hip Injection Versus Triamcinolone for Hip Osteoarthritis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hip Osteoarthritis
Keywords: bone marrow aspirate concentrate
triamcinolone
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Lisa Dean Moseley Foundation
First posted: 2021-08-04
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: bone marrow aspirate concentrate versus triamcinolone
Primary purpose: TREATMENT

Brief summary: 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: 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. Out of the bone aspirated, 60 cc will be utilized for concentration, 2 cc will be utilized by Bioscience Research Laboratory (BSR), and 2 cc will be stored in a -80°C biorepository enzyme-linked immunosorbent assay to determine concentrations of IL-1ra and other cytokines The 60 cc of unconcentrated bone marrow will then be concentrated to a total of 8 cc of concentrated bone marrow utilizing the Emcyte PureBMC™ system. Out of these 8 cc, 5 will be injected to the patient and the remainder 3 cc will be utilized for analyses.

These are the volumes and respective analyses:

* 1.5 cc will be directed to BSR for colony forming units, cell viability, total nucleated cell count as outlined in the subsequent paragaphs,
* 1 cc will be sent for 14 day culture
* 0.5 cc for endotoxin testing and gram stain

We 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/mL. We will abide by this limit.

Rapid sterility will be assessed using a gram stain, performed by a CLIA certified laboratory at Cleveland Clinic Florida.

To ensure patient safety, patient will be considered a screen failure if there is a positive Gram stain or positive endotoxin testing. The injection of the BMAC will not be subsequently injected.

The remaining 4 cc will be utilized as the intervention group injectate. The BMAC will be injected as is and will not undergo any manipulation and/or dilution.

The 4 cc BMAC dose or 1 cc triamcinolone of 40 mg with 3 cc of lidocaine 1% 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.

Eligibility criteria: Inclusion:

1. Provision of signed and dated consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged between 18 - 75 years old
4. WOMAC Pain Subscale With Average Score(Total WOMAC Pain Score Divided by 5) Equal to 4 or higher
5. Kellgren-Lawrence Grade greater than or equal to 2 on Hip X-Rays
6. Body Mass Index less than or equal to 35 kg/m2
7. Unilateral or Bilateral Hip Osteoarthritis
8. Prior physical therapy treatment for 6 weeks in the last 6 months
9. Agreement to adhere to Lifestyle Considerations (see section 5.3)
10. Discontinuation of pain/anti-inflammatory medications 2 week prior to baseline measurements
11. Patients with cancer in remission for at least 5 years. Specific cancers which were treated with surgical resection and are not undergoing chemotherapy/radiation therapy such as breast cancer, colon cancer, or skin cancer, and others could participate when deemed in remission for 1 year. Written approval from oncologist will be necessary prior to enrollment
12. Endotoxin less than or equal to 0.5 EU/ml
13. Negative gram stain result

Exclusion:

1. Prior corticosteroid injection to the hip
2. History of hip replacement(s)
3. Noncompliance to preventive screening tests for cancer indicated by age
4. Active autoimmune disease
5. Current use of oral corticosteroid
6. Use of immunosuppressive medications, or who are known to me immunocompromised
7. Inability to be weaned of oral anti-inflammatory medications
8. History of Diabetes or HbA1c \> 6.5%
9. Uncontrolled Thyroid Dysfunction: 0.450 uIU/mL ≥ TSH levels ≥ 4.500 uIU/mL
10. Vitamin D Level \< 30 ng/ml
11. Anemia (Hgb \< 11.7 g/dL for Women; Hgb \< 13 g/dL for men)
12. eGFR \< 60 mL/min/1.73 m2
13. Thrombocytopenia with platelet count less than 150,000 x 109 L
14. Patients with coagulopathies based on known clotting disorder
15. Patients currently on anti-coagulation therapies
16. Patients who report any active infection(s) including cellulitis, TB, HIV, COVID, Hepatitis B and C
17. Moving over the next year
18. Inability to consent to the research study
19. Inability to complete forms electronically
20. Subjects in any other clinical trials
21. History of allergic reaction to lidocaine
22. Pregnancy or planning to be pregnant during trial
23. Breastfeeding

Primary outcomes:
measure: Western Ontario McMaster Universities Arthritis Index (WOMAC)
timeFrame: 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.
measure: Western Ontario McMaster Universities Arthritis Index (WOMAC)
timeFrame: 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.
measure: Western Ontario McMaster Universities Arthritis Index (WOMAC)
timeFrame: 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.
measure: Western Ontario McMaster Universities Arthritis Index (WOMAC)
timeFrame: 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 outcomes:
measure: 6 Minute Walk Test (6MWT)
timeFrame: 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.
measure: 6 Minute Walk Test (6MWT)
timeFrame: 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.
measure: 6 Minute Walk Test (6MWT)
timeFrame: 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.
measure: 6 Minute Walk Test (6MWT)
timeFrame: 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.
Other outcomes:
measure: PROMIS - Physical Function (PROMIS-PF)
timeFrame: 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.
measure: PROMIS - Physical Function (PROMIS-PF)
timeFrame: 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.
measure: PROMIS - Physical Function (PROMIS-PF)
timeFrame: 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.
measure: PROMIS - Physical Function (PROMIS-PF)
timeFrame: 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.
measure: PROMIS - Pain Interference (PROMIS-PI)
timeFrame: 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.
measure: PROMIS - Pain Interference (PROMIS-PI)
timeFrame: 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.
measure: PROMIS - Pain Interference (PROMIS-PI)
timeFrame: 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.
measure: PROMIS - Pain Interference (PROMIS-PI)
timeFrame: 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.
measure: Global Rate of Change (GRoC)
timeFrame: 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.
measure: Global Rate of Change (GRoC)
timeFrame: 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.
measure: Global Rate of Change (GRoC)
timeFrame: 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.
measure: Global Rate of Change (GRoC)
timeFrame: 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.
measure: Pittsburgh Sleep Quality Index
timeFrame: 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.
measure: Pittsburgh Sleep Quality Index
timeFrame: 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.
measure: Pittsburgh Sleep Quality Index
timeFrame: 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.
measure: Pittsburgh Sleep Quality Index
timeFrame: 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.
Locations:
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
Study officials:
affiliation: Cleveland Clinic Florida
name: LEONARDO P OLIVEIRA, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic Florida
name: Carlos Higuera-Rueda, MD
role: STUDY_DIRECTOR
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