Autologous Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Femoral Head
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Johns Hopkins University
- Enrollment
- 192
- Locations
- 20
- Primary Endpoint
- Change in Pain using the Pain VAS scale
Study Overview
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.
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 Association Research Circulation Osseous (ARCO) Stage III or IV, Association Research Circulation Osseous (ARC)), 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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Masking Description
Participants will be blinded as to group assignment. Both groups will undergo a core decompression. One group will undergo a bone marrow aspiration and the other group will undergo a sham procedure. This sham procedure consists of a small incision and placing a needle up to the iliac bone but with no bone penetration or aspiration.
The study radiologists will be blinded as to patient treatment assignment; images will be assigned the patient study number and date only.
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants who have non-traumatic osteonecrosis of the femoral head
- •Only participants who have Stage 1 or 2 osteonecrosis as assessed by the 2019 ARCO Staging System
- •No evidence of subchondral fracture
- •All osteonecrotic lesion sizes
- •All major risk factors (e.g. corticosteroids, alcohol, organ recipient) except for those listed in the
Exclusion Criteria
- •Participants diagnosed who have femoral head osteonecrosis for which no risk factor has yet to be identified
- •Participants will include all ethnicities and races
- •Be able and willing to participate in study and return for postoperative visits
- •Exclusion Criteria
- •Participants who have:
- •Sickle Cell disease
- •Major trauma
- •Post-irradiation ON
- •Gaucher Disease
- •Juvenile form: Legg-Calve-Perthes Disease
- •Juvenile form: Spontaneous ON of the hip
- •Pregnant or breastfeeding
- •Vulnerable population; i.e., prisoners and institutionalized individuals
- •Participant is unable to undergo an MRI
- •Participants who have evidence of a subchondral fracture
- •Prior history of hip surgery, more extensive than hip arthroscopy
Arms & Interventions
Core decompression (CD)
Core decompression of the femoral head with sham bone marrow aspiration
Intervention: Core Decompression (Procedure)
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.
Intervention: Core Decompression (Procedure)
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.
Intervention: Core Decompression Procedure with Autologous Bone Marrow Aspirate Concentrate (Procedure)
Outcomes
Primary Outcomes
Change in Pain using the Pain VAS scale
Time Frame: Up to 24 months
This is assessed using the pain Visual Analogue Scale (VAS). The participant marks an X on a 10cm scale denoting the level of pain that they are experiencing. VAS measures pain intensity on a scale of 0 (no pain) to 10 (worst pain).
Radiological progression of osteonecrosis of the femoral head (ONFH) to ARCO Stage III or IV
Time Frame: Up to 24 months
The 2019 ARCO Staging System encompasses four stages. ARCO Stage I is the earliest stage of osteonecrosis and is characterized by a normal x-ray and an abnormal MRI. ARCO Stage IV is the most advanced stage of osteonecrosis and is characterized by findings of osteoarthritis on x-ray.
Time to failure of femoral head
Time Frame: Up to 24 months
Time is measured in months following the intervention (core decompression or core decompression with cells). Failure is defined as radiological progression to ARCO Stage III or IV or unremitting pain requiring surgical intervention.
Secondary Outcomes
- Change in Pain using the Hip disability and Osteoarthritis Outcome Score (HOOS)(Baseline, 6 months, 12 months, 24 months)
- Change in Symptoms and Stiffness using the HOOS(Baseline, 6 months, 12 months, 24 months)
- Change in Activities of Daily Living function using the HOOS(Baseline, 6 months, 12 months, 24 months)
- Change in Function in Sports and Recreational Activities using the HOOS(Baseline, 6 months, 12 months, 24 months)
- Change in Quality of Life using the HOOS(Baseline, 6 months, 12 months, 24 months)
- Change in Physical Health Composite Score using the PROMIS 10 Global Health Questionnaire(Baseline, 6 months, 12 months, 24 months)
- Change in Mental Health Composite Score using the PROMIS 10 Global Health Questionnaire(Baseline, 6 months, 12 months, 24 months)
- Change in Activity using the University of California Los Angeles (UCLA) Activity Rating Scale(Baseline, 6 months, 12 months, 24 months)