Autologous Bone Marrow Aspirate Treatment for Early-Stage Osteonecrosis

Avascular Necrosis of the Femoral Head Clinical Trial

— BATON  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06123481
• Other study ID #: IRB00289774
• Secondary ID: U01AR080993-01A1
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 10, 2024
• Est. completion date: August 9, 2028

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Lynne C Jones, PhD
• Phone: (410) 550-4001
• Email: ljones3[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 192
• Est. completion date: August 9, 2028
• Est. primary completion date: April 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Avascular Necrosis of the Femoral Head
• Necrosis
• Osteonecrosis
• Osteonecrosis of the Femoral Head

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	University of Southern California	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	NYU Langone Health Orthopedic Hospital	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Sinai Hospital of Baltimore, Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiological progression of osteonecrosis of the femoral head (ONFH) to ARCO Stage III or IV	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.	Up to 24 months
Primary	Change in Pain using the Pain VAS scale	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).	Up to 24 months
Primary	Time to failure of femoral head	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.	Up to 24 months
Secondary	Change in Pain using the Hip disability and Osteoarthritis Outcome Score (HOOS)	The Pain subscale of the Hip disability and Osteoarthritis Outcome Score (HOOS) will be used. The HOOS Pain sub-score is comprised of 10 items with a potential total of 40 points. Higher score worse pain,	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Symptoms and Stiffness using the HOOS	The Symptoms and Stiffness will be assessed using the HOOS Symptoms and Stiffness sub-score is comprised of 5 items with a potential total score of 20 points. Higher score worse stiffness.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Activities of Daily Living function using the HOOS	The HOOS Activities of Daily Living function sub-score is comprised of 17 items with a potential total of 68 points. Higher scores better functioning.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Function in Sports and Recreational Activities using the HOOS	The HOOS Function of Sports and Recreational Activities subscale is comprised of 4 items with a potential total of 16 points. Higher score better outcome.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Quality of Life using the HOOS	The HOOS Quality of Life subscale is comprised of 4 items with a potential total of 16 points. Higher score better quality of life.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Mental Health Composite Score using the PROMIS 10 Global Health Questionnaire	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.; PROMIS mental health survey. The measures are generic, rather than disease-specific, and use an "In General" item context as it is intended to globally reflect individuals' assessment of their health. It is a survey of 10 questions which gives a physical health and mental health score. The raw global health mental score (4-20) is converted to a mental health T score (16.2-67.7). The higher the score, the better the health outcome.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Physical Health Composite Score using the PROMIS 10 Global Health Questionnaire	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.; PROMIS physical health survey. The measures are generic, rather than disease-specific, and use an "In General" item context as it is intended to globally reflect individuals' assessment of their health. It is a survey of 10 questions which gives a physical health and mental health score. The raw global health physical score (4-20) is converted to a physical health T score (16.2-67.7). The higher the score, the better the health outcome.	Baseline, 6 months, 12 months, 24 months
Secondary	Change in Activity using the UCLA Activity Rating Scale	The UCLA Activity Score 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). The higher the level, the better the outcome.	Baseline, 6 months, 12 months, 24 months