Use of MRI Labeling Technique to Track Mesenchymal Stem Cell Survival in Orthopaedic Conditions

Effect of Surgical Intervention on Mesenchymal Stem Cell Survival in Soft Tissue Reconstructive Procedures Using a Novel MRI Labeling Technique

The primary objective is to determine whether a surgical intervention involving removing of the calcified cartilage cap in patients with Grade II Kellgren-Lawrence osteoarthritis influences the incorporation of labeled bone marrow aspirate concentrate (BMAC)-derived cells within the cartilage regenerate vs labeled BMAC cells delivered after arthroscopy without removing of the calcified cartilaginous layer. The survival and incorporation of the BMAC labeled cells will be evaluated with MRI using the Ferumoxytol infusion stem cell labeling technique. The second arm of the study evaluating cell fate after injecting stem cells under a rotator cuff repair will also be explored.

The secondary objectives are to 1) determine which surgical intervention leads to better clinical outcomes as measured by Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12 months, and 2) determine who long we can track the labeled-BMAC cells in the knee.

Study Overview

• Status: Withdrawn
• Conditions: Rotator Cuff Tear; Osteoarthritis, Knee; Cartilage Degeneration
• Intervention / Treatment: Procedure: arthroscopy of the affected knee/ Bone Marrow Concentrate Injection

Detailed Description

Articular cartilage repair and regeneration has become a focal point for scientists and surgeons in search for a biological treatment for osteoarthritis that has failed non-operative management. Surgeons have begun to harvest and centrifuged bone marrow aspirate to produce bone marrow aspirate concentrate (BMAC) in hopes that the mesenchymal stem cells in the bone marrow aspirate can stimulate cartilage regeneration in areas of articular cartilage deficiency. This study is a first-in-human blinded randomized clinical trial using labeled BMAC cells in adults diagnosed with grade II-III Kellgren-Lawrence osteoarthritis.

This is a single site study where 20 cases among eligible patients will be identified and randomly assigned to either the control (no calcified cartilage) or experimental (calcified cartilage removed) group. A power analysis will be performed after 20 patients to determine the total number of patients required to reach adequate power.

A patient will receive an infusion of Feraheme 2 days before the procedure and a baseline MR Pelvis and knee. A nurse will be present at all times during the infusion to monitor vitals. On the day of the procedure patient will undergo harvesting of the bone marrow from the pelvis and arthroscopy procedure involving menisectomy, synovectomy and debridement. Patients in the experimental group will also undergo removal of the calcified cartilage cap. The bone marrow aspirate will be centrifuged and about 5-7 cc of BMAC injected into knee. MRIs will be done at the 2 day mark for confirmation of the labeling of the mesenchymal cells, and at the two week and 3 month mark. Patient related Outcomes will be measured using the Knee injury and Osteoarthritis Score at 12 months follow up.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults aged 30-70 patients with Kellgren grade II-III osteoarthritis,
2. Symptomatic knee pain greater than 6 months
3. At least one discrete contained chondral defect
4. Failed a minimum of 6 weeks of physical therapy
5. Grossly normal knee alignment: <5 degrees of varus or valgus alignment
6. Lesion located on medial or lateral femoral condyle or trochlea

Exclusion Criteria:

1. Radiographs demonstrating either no or little osteoarthritis (Kellgren-Lawrence Grade 0 or 1)
2. Diagnosis of Inflammatory (RA, JIA etc) or infectious arthritis
3. Malalignment of mechanical axis > or = 5 degrees of varus/valgus
4. Cortisone and/or Hyaluronic acid intra-articular injection within the last 3 months
5. Ligamentous knee instability
6. The subject is on ongoing specific osteoarthritis drugs such as chondroitin sulphate, diacerein, N-glucosamine, piascledine, capsaicin in the 2 weeks prior to baseline treatment
7. BMI > 30
8. Currently pregnant or planning to become pregnant (no MRI possible).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arthroscopy with removal of calcified cartilage; This arm will have patients who will get surgical intervention (menisectomy, synovectomy and debridement) along with removal of the calcified cartilage layer. The patients will also get 5 cc of BMAC produced from The Harvest/Terumo BCT system.	Procedure: arthroscopy of the affected knee/ Bone Marrow Concentrate Injection; Subjects will undergo knee arthroscopy for debridement, menisectomy and synovectomy of the cartilage defects. Subjects will also be injected with bone marrow aspirate concentrated harvested from the pelvis and centrifuged (produced produced using the Harvest/Terumo BCT system); Other Names: Injection of bone marrow aspirate concentrate harvested from the patient's iliac crest (produced using the Harvest/Terumo BCT system)
Active Comparator: arthroscopy without removal of calcified cartilage; This arm will have patients who will get surgical intervention (menisectomy, synovectomy and debridement) but with retention of the calcified cartilage cap. The patients will also get 5 cc of BMAC produced from The Harvest/Terumo BCT system.	Procedure: arthroscopy of the affected knee/ Bone Marrow Concentrate Injection; Subjects will undergo knee arthroscopy for debridement, menisectomy and synovectomy of the cartilage defects. Subjects will also be injected with bone marrow aspirate concentrated harvested from the pelvis and centrifuged (produced produced using the Harvest/Terumo BCT system); Other Names: Injection of bone marrow aspirate concentrate harvested from the patient's iliac crest (produced using the Harvest/Terumo BCT system)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Integration of the mesenchymal stem cells.	Number of integrated labeled mesenchymal stem cells in the cartilage regenerate counted from from MRI imaging.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Injury and Osteoarthritis Outcome Score (pain subscale)	KOOS pain score at baseline and at 12 months to measure functional outcomes. This sub scale of the KOOS questionnaire has a possible total of 100 points (higher scores mean less pain)	12 months

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Lawrence Enweze, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 29, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Rupture; Shoulder Injuries; Tendon Injuries; Osteoarthritis; Rotator Cuff Injuries; Osteoarthritis, Knee
• Other Study ID Numbers: IRB-46711

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No