Autologous Bone Marrow Aspirate Treatment for Early-Stage Osteonecrosis

Official title

Autologous Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Femoral Head

Overview

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.

Interventions

• 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 milliliters of bone marrow aspirate concentrate into the necrotic femoral head through an opening created by the core decompression.

Primary outcome measures

• Radiological progression of osteonecrosis of the femoral head (ONFH) to ARCO Stage III or IV [Time frame: Up to 24 months]
• Change in Pain using the Pain VAS scale [Time frame: Up to 24 months]
• Time to failure of femoral head [Time frame: Up to 24 months]

Secondary outcome measures (8)

• Change in Pain using the Hip disability and Osteoarthritis Outcome Score (HOOS) [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Symptoms and Stiffness using the HOOS [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Activities of Daily Living function using the HOOS [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Function in Sports and Recreational Activities using the HOOS [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Quality of Life using the HOOS [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Mental Health Composite Score using the PROMIS 10 Global Health Questionnaire [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Physical Health Composite Score using the PROMIS 10 Global Health Questionnaire [Time frame: Baseline, 6 months, 12 months, 24 months]
• Change in Activity using the University of California Los Angeles (UCLA) Activity Rating Scale [Time frame: Baseline, 6 months, 12 months, 24 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 10 centers

• University of Southern California — Los Angeles
• Stanford University — Stanford
• Sinai Hospital of Baltimore — Baltimore
• Johns Hopkins University — Baltimore
• University of Minnesota — Minneapolis
• Mayo Clinic — Rochester
• NYU Langone Health Orthopedic Hospital — New York
• Cleveland Clinic — Cleveland
• … and 2 more centers

Identifiers

NCT: NCT06123481 · IRB00289774 · U01AR080993-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗