Clinical trial NCT06123481: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteonecrosis of the Femoral Head
Avascular Necrosis of the Femoral Head
Keywords: osteonecrosis
aseptic necrosis
avascular necrosis (AVN)
bone marrow aspirate
bone marrow aspirate concentrate
bone marrow cells
bone marrow
cell-based treatment
core decompression
femoral head
necrosis
bone diseases
musculoskeletal diseases
pathologic processes
hip
ONFH
AVN
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2023-11-08
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A 1:1 randomized, parallel design with two treatment arms: 1) core decompression (percutaneous drilling) alone, or 2) core decompression augmented with autogenous bone marrow aspirate. Cluster randomization will be performed at each participating institution.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Radiological progression of osteonecrosis of the femoral head (ONFH) to ARCO Stage III or IV
timeFrame: Up to 24 months
measure: Change in Pain using the Pain VAS scale
timeFrame: Up to 24 months
measure: Time to failure of femoral head
timeFrame: Up to 24 months
Secondary outcomes:
measure: Change in Pain using the Hip disability and Osteoarthritis Outcome Score (HOOS)
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Symptoms and Stiffness using the HOOS
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Activities of Daily Living function using the HOOS
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Function in Sports and Recreational Activities using the HOOS
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Quality of Life using the HOOS
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Mental Health Composite Score using the PROMIS 10 Global Health Questionnaire
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Physical Health Composite Score using the PROMIS 10 Global Health Questionnaire
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Change in Activity using the University of California Los Angeles (UCLA) Activity Rating Scale
timeFrame: Baseline, 6 months, 12 months, 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Langone Health Orthopedic Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Johns Hopkins University
name: Lynne C Jones, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sinai Hospital of Baltimore / LifeBridge Health
name: Michael A Mont, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Stuart B Goodman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: