Concentrated Bone Marrow Aspirate in Revision ACL Reconstruction

Anterior Cruciate Ligament Injuries Clinical Trial

Official title:

Multi-Center Pilot Study to Evaluate Concentrated Bone Marrow Aspirate (cBMA) as a Treatment to Modify Post-Traumatic Osteoarthritis (PTOA) Following Revision Anterior Cruciate Ligament Reconstruction (ACLR)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06311513
• Other study ID #: 2023-1017
• Secondary ID: 1177535
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 2024
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Hospital for Special Surgery, New York
• Contact: Daniel de la Huerta, MD
• Phone: 917-260-3159
• Email: delahuertamezad[@]hss.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this pilot randomized clinical trial is to look into the efficacy of concentrated bone marrow aspirate (cBMA) in improving post traumatic osteoarthritis (PTOA) symptoms in patients undergoing revision anterior cruciate ligament reconstruction surgery. The main questions it aims to answer are whether clinical outcomes, such as pain, are improved in patients who get cBMA with surgery, if there is a change in circulating markers of inflammation and what part of the cellular and molecular composition of cBMA may explain its effects.

Description:

Anterior cruciate ligament reconstruction (ACLR) surgery is considered a relatively safe and effective procedure, however, up to 18% of grafts will fail and require revision surgery. Some studies have shown that these patients may be at increased risk of worse clinical outcomes, including fast progression toward post-traumatic osteoarthritis (PTOA). This is likely in part due to the inflammatory environment created within the joint. Concentrated bone marrow aspirate (cBMA) is a regenerative medicine therapy that contains soluble factors and connective tissue progenitor cells which may have immunomodulatory and pro-regenerative potential. The use of this therapy in conjunction with standard of care surgical treatment may help reduce the inflammatory microenvironment inside the joint, therefore modifying the conditions that might lead to developing long term complications such as PTOA.

We hypothesize that cBMA treatment at the time of revision ACLR may improve clinical outcomes at 1 year after surgery and reduce the risk of developing PTOA-associated symptoms.

Participants will be randomized to either get a cBMA injection (investigational arm) at the time of surgery or a placebo incision (control arm). Biological specimens (blood, urine, synovial fluid), imaging data, functional tests and patient reported clinical outcomes will be measured at different time points during the study, for up to two years after the surgery. This will allow us to evaluate the effect of cBMA in clinical outcomes. Biological specimens will be analyzed using molecular biology techniques to determine their composition, including the concentration of cells and other inflammatory markers.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Males and Females

• Age 18 to 55

• Previous unilateral ACLR (Anterior Cruciate Ligament Reconstruction) within the last 5 years, and identified as having experienced failure of the primary ACLR

• Scheduled to have a revision ACLR surgery, with any graft type (including patellar tendon, hamstring, quad or allograft)

• Able to complete all study procedures and participate in a standardized physical therapy program

Exclusion Criteria:

• History of inflammatory arthritis or joint sepsis

• Prior or concurrent total or sub-total meniscectomy

• Prior or present avascular necrosis of the index knee

• Oral or intra-articular corticosteroid injection within 3 months

• Hyaluronic acid or PRP (Platelet-Rich Plasma) injection within 6 months

• Use of duloxetine, doxycycline, indomethacin, glucosamine and/or chondroitin (ongoing or within 2 months)

• Any clinical or laboratory abnormality greater than grade 3 CTCAE, which in the view of the investigator, will compromise the participant's safety.

• Planned arthroplasty in the index knee

Related Conditions & MeSH terms

• ACL Injury
• Anterior Cruciate Ligament Injuries
• Bone Marrow Aspirate Concentrate
• Osteoarthritis
• Osteoarthritis, Knee
• Post-Traumatic Osteoarthritis of Knee
• Wounds and Injuries

Intervention

Biological:
• Concentrated Bone Marrow Aspirate Injection
Intraoperatively, bone marrow will be harvested from the iliac crest with a commercial kit, it will then be prepared via centrifugation and an injection of the resulting concentrated product (cBMA) will be administered in the operative knee. cBMA is an autologous biologic product.

Procedure:
• Sham Incision
A 2 mm sham incision will be made in the anatomical site where bone marrow would be harvested.
• Revision Anterior Cruciate Ligament Reconstruction
This is the standard-of-care surgical procedure.

Locations

Country	Name	City	State
United States	Emory Orthopaedics & Spine Center	Atlanta	Georgia
United States	Hospital for Special Surgery	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York	Arthritis Foundation, Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in patient reported knee pain	The primary outcome measured for this study will be postoperative knee pain. This will be achieved using the Knee Injury and Osteoarthritis Outcome Score (KOOS) standardized questionnaire, which will be electronically delivered to participants at baseline and at 6-weeks, 6-months, 12-months and 24-months postoperatively. This questionnaire measures 42 items in a Likert scale for 5 different dimensions: pain, other symptoms, activities of daily living, function in sports and recreation and knee-related quality of life. The questionnaire is scored as a percentage from 0 to 100, with 0 representing extreme problems and 100 indicating no knee related symptoms.	Baseline, 6 weeks, 6 months, 12 months and 24 months post-operative
Secondary	Expression of local inflammatory biomarkers	Synovial fluid collected before and 6 weeks after surgery will be analyzed using ELISA panels, looking for expression and concentration of markers of inflammation (e.g. IL-1ß, TNFa) and matrix remodeling (COMP, CTXII)	Baseline and 6 weeks post-operative
Secondary	Concentration of circulating inflammatory biomarkers	Biological samples (urine and blood) will be collected intraoperatively, and at 6-weeks and 12-months post-operatively. Samples will be processed and analyzed using ELISA panels, looking for the circulating concentration of markers of inflammation (e.g. IL-1ß, TNFa) and matrix remodeling (COMP, CTXII).	Baseline, 6 weeks and 12 months post-operative
Secondary	Change from baseline in cartilage morphology	Proton density weighted fast-spin-echo images will be acquired to assess cartilage morphology preoperatively and at 12 months post-operatively. Findings will be scored using the MRI Osteoarthritis Knee Score (MOAKS), which establishes criteria for assessing lesion grade (from 0 - best to 3 - worst) in fourteen distinct subregions.	Baseline, 12 months post-operative
Secondary	Change from baseline in articular cartilage relative proteoglycan content and collagen fibril organization	Combined T1?-T2 quantitative MRI image acquisition protocol will help determine the changes in relative proteoglycan content and collagen fibril organization within the knee articular cartilage.	Baseline, 12 months postoperative