Bone Marrow Derived Stem Cells for the Treatment of Rotator Cuff Tears

Randomized Control Trial of Bone Marrow Derived Stem Cells Combined With Arthroscopic Surgery Versus Arthroscopic Surgery Only for the Treatment of Rotator Cuff Tears

The primary objective is to determine whether adjunct treatment using bone marrow aspirate concentrate (BMAC) in conjunction with arthroscopic repair of rotator cuff tears reduces retear rates compared to a control population undergoing arthroscopic repair without BMAC administration. The secondary objectives are to (1) evaluate the survival and incorporation of BMAC labeled cells with MRI imaging using the Ferumoxytol infusion stem cell labeling technique, and (2) determine if administration of BMAC leads to better clinical outcomes as measured by ASES, UCLA and Constant scoring metrics.

Study Overview

• Status: Withdrawn
• Conditions: Rotator Cuff Tear; Rotator Cuff Injury
• Intervention / Treatment: Procedure: Arthroscopic rotator cuff repair with bone marrow aspirate concentrate; Procedure: Arthroscopic rotator cuff repair

Detailed Description

Rotator cuff repair and regeneration has become a focal point for scientists and surgeons in search for a biological treatment to improve tendon healing, especially in situations of unfavorable biological conditions. Recent literature supports harvesting and centrifuging bone marrow aspirate to produce bone marrow aspirate concentration (BMAC) in hopes that mesenchymal stem cells in the bone marrow aspirate can promote tendon healing and regeneration.

This is a single blinded randomized clinical trial using labeled BMAC cells in adults diagnosed with medium to large, single tears of the rotator cuff. This is a single site study where at least 45 cases among eligible patients will be identified and randomly assigned to a either a control (arthroscopic repair without BMAC) group or experimental (arthroscopic repair with BMAC) group. A power analysis will be performed after enrolling 20 patients to determine the total number of patients required to reach adequate power.

A patient will receive an infusion of Ferumoxytol 1 day prior to the surgical procedure. An infusion nurse will be present at all times during the infusion to monitor vitals. On the day of the surgical procedure patients in the both groups will undergo arthroscopic rotator cuff repair using a double-row technique. Patients in the experimental group will also undergo harvesting of bone marrow aspirate from the anterior inferior iliac crest, which will be centrifuged to about 3-4cc of BMAC and placed beneath the tendon at the bone interface. MRIs will be completed on days 1 and 7 post-operatively to track retention of the labeled mesenchymal cells. Ultrasound imaging will be performed at 6 months post-surgery to evaluate tendon healing. Final MRIs will be obtained at 1 year and 2 years post surgery. Patient related outcomes will be collected at the pre-operative visit, 3 months, 6 months, 1 year and 2 years post surgery in the forms of ASES, UCLA and Constant scoring.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 50-75 patients with MRI confirmed rotator cuff tears sized 1.5-3cm including supraspinatus with or without an associated partial infraspinatus or subscapularis tear
• Chronic tear > 3 months
• Failed a minimum of 6 weeks of physical therapy
• Hamada stage 1
• Goutallier staging < 3

Exclusion Criteria:

• Radiographs demonstrating mild to moderate arthritis
• Diagnosis of Inflammatory (RA, JIA etc) or infectious arthritis
• Hamada stage > 2
• Cortisone and/or Hyaluronic acid intra-articular injection within the last 3 months
• Brachial plexus pathology
• Currently pregnant or planning to become pregnant
• Shoulder PRP injection within the last year
• History of iron overload syndrome
• Concurrent surgery for shoulder instability

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: Shoulder arthroscopy with BMAC; This arm will have patients who receive surgical intervention with arthroscopic rotator cuff repair along with 3-4cc of BMAC produced from the Harvest/Terumo BCT system	Procedure: Arthroscopic rotator cuff repair with bone marrow aspirate concentrate; Subjects will undergo shoulder arthroscopy for rotator cuff repair using a double row technique. Subjects will also be injected with bone marrow aspirate concentrate harvested from the pelvis and centrifuged prior to injection in the shoulder (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: Shoulder arthroscopy alone; This arm will have patients who receive surgical intervention with arthroscopic rotator cuff repair without administration of BMAC.	Procedure: Arthroscopic rotator cuff repair; Subjects will undergo shoulder arthroscopy for rotator cuff repair using a double row technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tendon healing rates	Percent of rotator cuff repairs that demonstrate full healing at 2 years post surgery	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UCLA Score	UCLA score (0-35 points; higher score is better) at 24 months post surgery to measure functional outcome.	Date of enrollment to 24 months post-operatively
ASES Score	American Shoulder and Elbow Surgeons Shoulder Score (ASES) (0-100 points; higher score is better) at 24 months to measure functional outcome.	Date of enrollment to 24 months post-operatively
Constant Score	Constant score (0-100 points; higher score is better) at 24 months.	Date of enrollment to 24 months post-operatively
Retention of the mesenchymal stem cells	Imaging of labeled mesenchymal stems cells in the shoulder to assess retention post injection	7 days

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jason L Dragoo, Stanford University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: September 21, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Biologics; Bone marrow aspirate
• Additional Relevant MeSH Terms: Wounds and Injuries; Rupture; Shoulder Injuries; Tendon Injuries; Rotator Cuff Injuries
• Other Study ID Numbers: IRB-47762

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: No