BATON: Autologous Bone Marrow Aspirate Treatment for Early-Stage Osteonecrosis
Study Details
Study Description
Brief Summary
Osteonecrosis of the femoral head (ONFH) is a debilitating musculoskeletal disease that is characterized by localized death of bone cells and associated cellular elements within the subchondral bone. If it progresses, it results in the collapse of the femoral head (ball part of the hip) giving rise to secondary arthritis. This condition is associated with marked pain and loss of function, often necessitating a joint replacement. Due to the relatively young age of onset of ONFH (often in 20s and 30s), there is great interest in utilizing joint-preserving procedures prior to the need for joint replacement. Joint-preserving procedures include core decompression (CD) with and without bone grafts or cells, vascularized and non-vascularized bone grafting, as well as osteotomies. Inconsistent results for each of these procedures have been reported and there are no Clinical Practice Guidelines or medical community consensus opinions regarding the treatment of early-stage ONFH. The hypothesis to be tested is "Participants who have early-stage ONFH undergoing CD augmented with autogenous bone marrow aspirate concentrate will have better clinical and radiological outcomes than CD alone." This multi-center randomized controlled trial for early-stage ONFH is prospective and controlled for participant stage (only early-stage pre-collapse individuals) and surgical technique. Participants will be evaluated as per routine surgical follow-up, and at 6 months (telemedicine), 1- and 2- years using radiographs, MRIs, and questionnaires. This project will also explore the scientific basis for success vs. failure in individuals who have osteonecrosis, and have different demographics and bone marrow aspirate cell profiles.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Rationale. It is estimated that there are 10,000 to 20,000 new cases of osteonecrosis of the femoral head diagnosed each year in the United States. Several approaches to treatment have been undertaken including nonsurgical (e.g., pharmaceuticals, hyperbaric oxygen) and surgical (e.g., core decompression, bone grafting (both non-vascularized and vascularized), osteotomies, total joint replacement). Total joint replacement is performed to treat end-stage disease (when the joint goes "out-of-round", and cartilage damage has occurred). There has been increasing interest in using cell-based treatment with core decompression (CD) to treat early-stage osteonecrosis. Bone marrow aspirate concentrate (BMAC) injected into the CD is being evaluated in this study as it contains progenitor cells and other elements that have been shown to facilitate the development of bone and blood vessels. There is a need for rigorous, randomized controlled studies to determine the effectiveness of this cell-based treatment for osteonecrosis of the femoral head (ONFH).
Objectives. The goal of this study is to compare the clinical and radiological results of core decompression with autologous bone marrow aspirate concentrate to core decompression alone (CD). The results will be based on: 1) evidence of radiological progression of ONFH, 2) time to radiological progression of ONFH to ARCO Stage III or IV, [ARCO: Association Research Circulation Osseous, the international society for the study of osteonecrosis and other disorders of bone circulation] or 3) pain requiring surgical intervention. Success will be based on survivorship of the femoral head over the course of the study. Failure of the procedure is based upon evidence of radiographic progression to ARCO Stage III or pain requiring a surgical intervention.
Overall Design. This is a prospective, multi-center, interventional clinical trial being conducted to evaluate two treatments for early stage ONFH. Participants will be 1:1 randomized to one of two arms: 1) BMAC: Core decompression augmented with autogenous bone marrow aspirate concentrate; 2) CD: Core decompression alone. The core decompression and bone marrow aspiration and concentration will be performed according to a standardized protocol. The CD group will also undergo a sham procedure consisting of a small incision and placing the needle up to the iliac bone without marrow aspiration. In the BMAC group, a sample of the bone marrow aspirate concentrate will be submitted for laboratory assessments to identify the constituent cells and major biological pathways involved. Clinical Research Forms (pre-operatively; 6-, 12-, and 24-months post-operatively), radiographs, and MRIs (pre-operatively; 12- and 24-months post-operatively) will be performed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Core decompression (CD) Core decompression of the femoral head with sham bone marrow aspiration |
Procedure: Core Decompression
Standard core decompression procedure is performed by drilling into the necrotic bone of the femoral head. A sham bone marrow aspiration involves advancing a needle to the iliac crest (no bone penetration, no bone marrow aspiration) through a small skin incision.
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| Experimental: Bone Marrow Aspirate Concentrate (BMAC) Autologous bone marrow aspiration is concentrated and injected into the necrotic bone of the femoral head through the core decompression opening. |
Procedure: Core Decompression
Standard core decompression procedure is performed by drilling into the necrotic bone of the femoral head. A sham bone marrow aspiration involves advancing a needle to the iliac crest (no bone penetration, no bone marrow aspiration) through a small skin incision.
Procedure: Core Decompression Procedure with Autologous Bone Marrow Aspirate Concentrate
This involves bone marrow aspiration, concentrating the bone marrow aspirate, and injecting 6 millilters of bone marrow aspirate concentrate into the necrotic femoral head through an opening created by the core decompression.
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Outcome Measures
Primary Outcome Measures
- Radiological progression of osteonecrosis of the femoral head (ONFH) to ARCO Stage III or IV [24 months]
The 2019 ARCO Staging System encompasses four stages, published by Yoon et al. in the Journal of Arthroplasty in 2020 [ARCO: Association Research Circulation Osseous]. ARCO Stages I or II (entry stages for the study) have a round femoral head with no radiological evidence (x-ray, MRI) of subchondral fracture or collapse, whereas ARCO Stages III and IV have a nonspherical femoral head and evidence of subchondral fracture or collapse.
- Pain requiring surgical intervention (hip arthroplasty) as assessed by the pain visual analogue scale [24 months]
This is defined as persistent debilitating pain requiring hip arthroplasty. This is supported by the physical examination, pain visual analogue scale (VAS). VAS measures pain intensity on a scale of 0 (no pain) to 10 (worst pain).
- Pain requiring surgical intervention (hip arthroplasty) as assessed by the Hip disability and Osteoarthritis Outcome Score (HOOS) [24 months]
This is defined as persistent debilitating pain requiring hip arthroplasty. This is supported by the physical examination, and the pain subscale of the Hip disability and osteoarthritis outcome score (HOOS). The HOOS pain sub-score has 10 items with a potential total score of 0-40 points. Lower score indicating extreme problems.
- Time (in months) to failure of femoral head [Up to 24 months]
Failure is defined as radiological progression to ARCO Stage III or IV or unremitting pain requiring surgical intervention within xxx months.
Secondary Outcome Measures
- Change in hip pain as assessed by the visual analog scale (VAS) [Baseline, 6 months, 12 months, 24 months]
Pain is assessed using the self-reported visual analogue scale (VAS). The scale ranges from 0 (no pain) to 10 (worst pain).
- Need for a second surgery [24 months]
Progression to ARCO Stages III or IV or unremitting pain may require treatment with additional surgical intervention (hip arthroplasty). As the medical condition of the participant or their preference to wait may delay or preclude the scheduling of the hip arthroplasty, the need for additional surgical intervention is the outcome.
- Radiological Progression [Up 10 24 months]
This is defined as radiological progression to a more advanced stage of osteonecrosis as defined by the Association Research Circulation Osseous (ARCO) 2019 Staging System.
- Change in Pain subscale of the Hip disability and Osteoarthritis Outcome Score (HOOS) [Baseline, 6 months, 12 months, 24 months]
The HOOS Pain sub-score is comprised of 10 items with a potential total of 40 points.
- Change in Symptoms and Stiffness subscale of the HOOS [Baseline, 6 months, 12 months, 24 months]
The HOOS Symptoms and Stiffness sub-score is comprised of 5 items with a potential total score of 20 points.
- Change in Activities of Daily Living subscale of HOOS [Baseline, 6 months, 12 months, 24 months]
The HOOS Activities of Daily Living sub-score is comprised of 17 items with a potential total of 68 points.
- Change in Function in Sports and Recreational Activities subscale of HOOS [Baseline, 6 months, 12 months, 24 months]
The HOOS Function of Sports and Recreational Activities subscale is comprised of 4 items with a potential total of 16 points.
- Change in Quality of Life subscale of HOOS [Baseline, 6 months, 12 months, 24 months]
The HOOS Quality of Life subscale is comprised of 4 items with a potential total of 16 points.
- Change in Mental Health Composite Score of the PROMIS 10 Global Health Questionnaire [Baseline, 6 months, 12 months, 24 months]
The Patient-Reported Outcomes Measurement Information System (PROMIS) 10 Global Questionnaire is a 10-item patient-reported outcomes measure. A Mental Health Composite Score is generated as a summary of 4 items. Item responses range from 5 = None to 1 = Very Severe. The raw scores are converted into a T-score. Range 0 - 100; Population mean 50, standard deviation 10.
- Change in Physical Health Composite Score of the PROMIS 10 Global Health Questionnaire [Baseline, 6 months, 12 months, 24 months]
The Patient-Reported Outcomes Measurement Information System (PROMIS) 10 Global Questionnaire is a 10-item patient-reported outcomes measure. A Physical Health Composite Score is generated from the PROMIS 10 Global Questionnaire as a summary of 4 items. Item responses range from 5 = None to 1 = Very Severe. The raw scores are converted into a T-score. Range 0 - 100; Population mean 50, standard deviation 10.
- Change in UCLA Activity Rating Scale [Baseline, 6 months, 12 months, 24 months]
The UCLA (University of California, Los Angeles) Activity Score, published by Zahiri et al. in the Journal of Arthroplasty in 1998, ranks the level of participant activity on a 10-point scale based on descriptors of activity ranging from wholly inactive and dependent on others, cannot leave residence (Level 1) to regular participation in impact sports such as tennis, skiing, acrobatics, ballet, heavy labor, or backpacking (Level 10).
Eligibility Criteria
Criteria
Inclusion Criteria
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Participants who have non-traumatic osteonecrosis of the femoral head
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Only participants who have Stage 1 or 2 ARCO (2019) osteonecrosis; no evidence of subchondral fracture
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All osteonecrotic lesion sizes
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All major risk factors (e.g. corticosteroids, alcohol, organ recipient) except for those listed in the exclusion criteria
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Participants diagnosed who have femoral head osteonecrosis for which no risk factor has yet to be identified
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Participants will include all ethnicities and races
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Be able and willing to participate in study and return for postoperative visits
Exclusion Criteria
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Participants who have:
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Sickle Cell disease
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Major trauma
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Post-irradiation ON
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Gaucher Disease
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Juvenile form: Legg-Calve-Perthes Disease
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Juvenile form: Spontaneous ON of the hip
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Pregnant or breastfeeding
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Vulnerable population (i.e., prisoners and institutionalized individuals)
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Participant is unable to undergo an MRI
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Participants who have evidence of a subchondral fracture
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Prior history of hip surgery, more extensive than hip arthroscopy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Southern California | Los Angeles | California | United States | 90033 |
| 2 | Stanford University | Stanford | California | United States | 94063 |
| 3 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 4 | Johns Hopkins University | Baltimore | Maryland | United States | 21224 |
| 5 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 6 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 7 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 8 | NYU Langone Health Orthopedic Hospital | New York | New York | United States | 11016 |
| 9 | Duke University | Durham | North Carolina | United States | 27560 |
| 10 | Cleveland Clinic | Cleveland | Ohio | United States | 441195 |
| 11 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 12 | University of Virginia | Charlottesville | Virginia | United States | 22903 |
Sponsors and Collaborators
- Johns Hopkins University
- Stanford University
- Sinai Hospital of Baltimore
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
- Principal Investigator: Lynne C Jones, PhD, Johns Hopkins University
- Principal Investigator: Michael A Mont, MD, Sinai Hospital of Baltimore / LifeBridge Health
- Principal Investigator: Stuart B Goodman, MD, PhD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00289774
- U01AR080993-01A1