Concentrated Bone Marrow Aspirate in Revision ACL Reconstruction

March 8, 2024 updated by: Hospital for Special Surgery, New York

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)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30097
        • Emory Orthopaedics & Spine Center
    • New York
      • New York, New York, United States, 10021
        • Hospital for Special Surgery
        • Contact:
        • Principal Investigator:
          • Miguel Otero, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Investigational Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get an intraoperative injection of concentrated bone marrow aspirate (cBMA).
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.
Other Names:
  • cBMA
  • BMAC
  • Bone Marrow Aspirate Concentrate
Procedure: Revision Anterior Cruciate Ligament Reconstruction
This is the standard-of-care surgical procedure.
Other Names:
  • Revision ACLR
Sham Comparator: Control Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get a sham incision in lieu of bone marrow harvesting.
Procedure: Revision Anterior Cruciate Ligament Reconstruction
This is the standard-of-care surgical procedure.
Other Names:
  • Revision ACLR
Procedure: Sham Incision
A 2 mm sham incision will be made in the anatomical site where bone marrow would be harvested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in patient reported knee pain
Time Frame: Baseline, 6 weeks, 6 months, 12 months and 24 months post-operative
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expression of local inflammatory biomarkers
Time Frame: Baseline and 6 weeks post-operative
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-1β, TNFα) and matrix remodeling (COMP, CTXII)
Baseline and 6 weeks post-operative
Concentration of circulating inflammatory biomarkers
Time Frame: Baseline, 6 weeks and 12 months post-operative
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-1β, TNFα) and matrix remodeling (COMP, CTXII).
Baseline, 6 weeks and 12 months post-operative
Change from baseline in cartilage morphology
Time Frame: Baseline, 12 months post-operative
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
Change from baseline in articular cartilage relative proteoglycan content and collagen fibril organization
Time Frame: Baseline, 12 months postoperative
Combined T1ρ-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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital for Special Surgery, New York

Collaborators

Emory University
Arthritis Foundation

Investigators

  • Principal Investigator: Miguel Otero, Ph.D., Hospital for Special Surgery, New York

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

March 8, 2024

First Submitted That Met QC Criteria

March 8, 2024

First Posted (Actual)

March 15, 2024

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-1017
  • 1177535 (Other Grant/Funding Number: Arthritis Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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