Bone Marrow Aspirate Concentrate Versus Triamcinolone Injection For Hip Osteoarthritis

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

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.

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.

Participant will undergo a sham bone needling if assigned to Triamcinolone group to keep patient blinded to their intervention. This will simulate the bone marrow aspiration process. Outcomes assessor will receive de-identified data including the treatment type.

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.

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.

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.

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.

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.

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.

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.

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.

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.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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 weeks.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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 weeks.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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.

All PROMIS instruments are calibrated to a mean t-score of 50 with a standard deviation of 10, with greater scores indicating more of the health domain in question (i.e., higher PROMIS-PF scores indicate greater function, whereas higher PROMIS-PI scores indicate that pain has a greater detriment on quality of life)

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.

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 weeks.

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.

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.

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.

The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.

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 weeks.

The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.

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.

The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.

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.

The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.

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.

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

Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1323-30. doi: 10.1136/annrheumdis-2013-204763. Epub 2014 Feb 19.

Hootman JM, Helmick CG, Barbour KE, Theis KA, Boring MA. Updated Projected Prevalence of Self-Reported Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation Among US Adults, 2015-2040. Arthritis Rheumatol. 2016 Jul;68(7):1582-7. doi: 10.1002/art.39692.

Duclos M. Osteoarthritis, obesity and type 2 diabetes: The weight of waist circumference. Ann Phys Rehabil Med. 2016 Jun;59(3):157-160. doi: 10.1016/j.rehab.2016.04.002. Epub 2016 May 19.

Courties A, Sellam J. Osteoarthritis and type 2 diabetes mellitus: What are the links? Diabetes Res Clin Pract. 2016 Dec;122:198-206. doi: 10.1016/j.diabres.2016.10.021. Epub 2016 Nov 5.

Quinn RH, Murray J, Pezold R, Hall Q. Management of Osteoarthritis of the Hip. J Am Acad Orthop Surg. 2018 Oct 15;26(20):e434-e436. doi: 10.5435/JAAOS-D-18-00351.

Kruse DW. Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe? Curr Rev Musculoskelet Med. 2008 Dec;1(3-4):227-33. doi: 10.1007/s12178-008-9029-0.

Hashmi SK. Basics of Hematopoietic Cell Transplantation for Primary Care Physicians and Internists. Prim Care. 2016 Dec;43(4):693-701. doi: 10.1016/j.pop.2016.07.003.

Charlesworth J, Fitzpatrick J, Perera NKP, Orchard J. Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee. BMC Musculoskelet Disord. 2019 Apr 9;20(1):151. doi: 10.1186/s12891-019-2525-0.

Walters MC. Update of hematopoietic cell transplantation for sickle cell disease. Curr Opin Hematol. 2015 May;22(3):227-33. doi: 10.1097/MOH.0000000000000136.

Kim GB, Seo MS, Park WT, Lee GW. Bone Marrow Aspirate Concentrate: Its Uses in Osteoarthritis. Int J Mol Sci. 2020 May 2;21(9):3224. doi: 10.3390/ijms21093224.

Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455. Epub 2016 Sep 30.

Rodriguez-Fontan F, Piuzzi NS, Kraeutler MJ, Pascual-Garrido C. Early Clinical Outcomes of Intra-Articular Injections of Bone Marrow Aspirate Concentrate for the Treatment of Early Osteoarthritis of the Hip and Knee: A Cohort Study. PM R. 2018 Dec;10(12):1353-1359. doi: 10.1016/j.pmrj.2018.05.016. Epub 2018 May 29.

Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, Hosseini SE, Niknejadi M, Moeininia F, Aghahossein Fanni A, Baghban Eslaminejhad R, Vosough Dizaji A, Labibzadeh N, Mirazimi Bafghi A, Baharvand H, Aghdami N. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015 Jun;18(6):336-44.

McIntyre JA, Jones IA, Han B, Vangsness CT Jr. Intra-articular Mesenchymal Stem Cell Therapy for the Human Joint: A Systematic Review. Am J Sports Med. 2018 Dec;46(14):3550-3563. doi: 10.1177/0363546517735844. Epub 2017 Nov 3.

Hernigou P, Trousselier M, Roubineau F, Bouthors C, Chevallier N, Rouard H, Flouzat-Lachaniette CH. Stem Cell Therapy for the Treatment of Hip Osteonecrosis: A 30-Year Review of Progress. Clin Orthop Surg. 2016 Mar;8(1):1-8. doi: 10.4055/cios.2016.8.1.1. Epub 2016 Feb 13.

Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop. 2016 Aug;40(8):1755-1765. doi: 10.1007/s00264-016-3162-y. Epub 2016 Mar 30. Erratum In: Int Orthop. 2018 Jan;42(1):223.

Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord. 2015 Sep 18;16:258. doi: 10.1186/s12891-015-0714-z.

Piuzzi NS, Mantripragada VP, Sumski A, Selvam S, Boehm C, Muschler GF. Bone Marrow-Derived Cellular Therapies in Orthopaedics: Part I: Recommendations for Bone Marrow Aspiration Technique and Safety. JBJS Rev. 2018 Nov;6(11):e4. doi: 10.2106/JBJS.RVW.18.00007. No abstract available.

Friedlis MF, Centeno CJ. Performing a Better Bone Marrow Aspiration. Phys Med Rehabil Clin N Am. 2016 Nov;27(4):919-939. doi: 10.1016/j.pmr.2016.06.009.

Rezende MU, Gurgel HMC, Ocampos GP, Campos GC, Frucchi R, Pailo AF, Pasqualin T, Vicente JRN, Camargo OP. IMPROVEMENTS IN HIP OSTEOARTHRITIS WITH LAVAGE, TRIAMCINOLONE AND HYLAN G-F20. Acta Ortop Bras. 2020 Nov-Dec;28(6):280-286. doi: 10.1590/1413-785220202806240075.

Skwara A, Ponelis R, Tibesku CO, Rosenbaum D, Fuchs-Winkelmann S. Gait patterns after intraarticular treatment of patients with osteoarthritis of the knee--hyaluronan versus triamcinolone: a prospective, randomized, doubleblind, monocentric study. Eur J Med Res. 2009 Apr 16;14(4):157-64. doi: 10.1186/2047-783x-14-4-157.

Martin RL, Philippon MJ. Evidence of reliability and responsiveness for the hip outcome score. Arthroscopy. 2008 Jun;24(6):676-82. doi: 10.1016/j.arthro.2007.12.011. Epub 2008 Mar 12.