Varying Bone Marrow-Derived Mesenchymal Stem Cells Concentrations' Impact on Rotator Cuff Repair Outcomes

NCT06361797 | Withdrawn DMC

• 1 other identifier: IRB00415412
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Randomized controlled trial comparing benefits of varying amounts of proximal humerus-derived bone marrow aspirate and bone marrow concentrate in rotator cuff repair.

Conditions

Rotator Cuff Tears

Keywords

rotator cuff tear; bone marrow aspirate; bone marrow; double-row transosseous technique

Outcome Measures

Primary Outcomes (1)

• Number of Rotator cuff re-tears as assessed by magnetic resonance imaging

  Re-tear of the rotator cuff as determined by magnetic resonance imaging of the shoulder. Assessors will review blinded imaging to determine if there was a retear on MRI.

  6 months post-operatively

Secondary Outcomes (6)

• American Shoulder and Elbow Surgeons Score

  Pre-surgery, 2 weeks post-surgery, 1 month post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery, 24 months post-surgery

• Visual Analogue Pain Score

  Pre-surgery, 2 weeks post-surgery, 1 month post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery, 24 months post-surgery

• Subjective Shoulder Value score

  Pre-surgery, 2 weeks post-surgery, 1 month post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery, 24 months post-surgery

• Comprehensive Shoulder Assessment

  Pre-surgery, 2 weeks post-surgery, 1 month post-surgery, 3 months post-surgery, 6 months post-surgery, 12 months post-surgery, 24 months post-surgery

• Revision surgery rate

  Up to 2 years.

Study Arms (3)

4cc bone marrow aspirate

ACTIVE COMPARATOR

Bone marrow aspirate, 4cc

Other: Rotator cuff repair augmented with whole bone marrow

20cc bone marrow aspirate

EXPERIMENTAL

Bone marrow aspirate, 20cc

Other: Rotator cuff repair augmented with whole bone marrow

Bone marrow concentrate

EXPERIMENTAL

20cc of whole bone marrow concentrated (varying quantities)

Other: Rotator cuff repair augmented with concentrated bone marrow

Interventions

Rotator cuff repair augmented with whole bone marrow OTHER

Bone marrow derived from the proximal humerus will be aspirated during the rotator cuff repair. At the end of the procedure, the aspirate will be injected back into the joint space.

Also known as: Whole bone marrow, Bone marrow aspirate

20cc bone marrow aspirate; 4cc bone marrow aspirate

Rotator cuff repair augmented with concentrated bone marrow OTHER

Bone marrow derived from the proximal humerus will be aspirated during the rotator cuff repair. This volume will be concentrated and, at the end of the procedure, the concentrate will be injected back into the joint space.

Also known as: Bone marrow-derived mesenchymal stem cells, Bone marrow concentrate

Bone marrow concentrate

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a primary symptomatic fully repairable rotator cuff tear ranging between 1.0 to 4.0 cm involving the supraspinatus and/or infraspinatus that is amenable to a double-row transosseous equivalent (TOE) repair.
• Subject's rotator cuff tear must be repaired arthroscopically.
• Subject has failed at least 6 weeks of conservative management, from symptoms onset, of at least 2 conservative treatments including oral pain medications \[including but not limited to non-narcotics, NSAIDs, acetaminophen as per labeling of the medications\], chiropractic care, rest and structured physical therapy or exercise program prescribed by physical therapist, chiropractor provider or physician specifically for the treatment of rotator cuff tear injuries; or demonstrates the presence of unacceptable progressive symptoms or signs of acute functional deficit or intractable pain for which conservative care as noted above is otherwise not indicated.
• Subject has full passive movement of the arm comparable to the normal unaffected shoulder.
• Subject agrees to not use any NSAIDs e.g., naproxen, high dose aspirin, ibuprofen, Meloxicam, Diclofenac, etc., and/or acetaminophen for 1 week (7 days) prior to baseline, 2 weeks (14 days) prior to surgery and for 6 weeks post-surgery with the exception of low dose aspirin. In addition, the subject must agree to not use these products within 5 days of each follow-up visit starting with the 3-month visit, so as not to introduce confounding factors for assessments.
• Subject is willing and able to return for protocol required follow-up visits.
• Subject is willing and able to voluntarily sign the Institutional Review Board (IRB) approved Informed Consent.
• All genders, races, and ethnicities will be included.

You may not qualify if:

• Subject has any of the following conditions in the index shoulder: loss of ligaments, known neuromuscular or neurovascular compromise, deltoid deficiency (defect, tear, palsy), Samilson-Prieto Grade \> 2 for osteoarthritis of glenohumeral joint, subject has a Goutallier Grade ≥3 fatty infiltration, history within the past 5 years of anterior or posterior shoulder subluxation or dislocation as determined by history, examination or radiographic findings.
• Subject's condition is bilateral and rotator cuff repair is scheduled or is to be scheduled over the course of this study for the contralateral shoulder.
• Subject requires concurrent fracture repair or reconstruction of the index shoulder.
• Subject has any of the following conditions: thrombocytopenia, anemia, platelet dysfunction syndrome, hemodynamic instability or septicemia.
• Subject has had a recent fever or illness.
• Subject has prior rotator cuff tendon repair, or ≥2 prior corticosteroid injections in the index shoulder.
• Subject has an underlying metabolic bone disease (e.g., Paget's disease, fibrous dysplasia, osteoporosis).
• Subject is at a higher risk for post-surgical bleeding (e.g., bleeding disorders; taking anticoagulants except low dose aspirin) or post-surgical infection (e.g., taking immunosuppressants; has a severe infection or recent use of systemic steroids).
• Subject has a known collagen disorder, including systemic lupus erythematous (SLE), rheumatoid arthritis (RA), polymyositis, scleroderma, ankylosing spondylitis, dermatomyositis, osteogenesis imperfecta or the inherited disorders of Sjogren, Larsen, Raynaud, Ehlers-Danlos or Marfan syndrome.
• Subject has any disease, condition or surgery which in the opinion of the investigator might impair healing, such as an active malignancy, history of metastatic malignancy, inflammatory or auto-immune based joint disease.
• Subject has evidence of a systemic infection, infection of the index shoulder or infection of the shoulder joint or overlying tissue such as septic arthritis, overlying cellulitis, or adjacent osteomyelitis.
• Subject has history of peripheral or central vascular disease, renal dysfunction, liver disease, chronic obstructive pulmonary disease, uncontrolled asthma, coagulopathies, cancers aside from basal cell carcinomas, uncontrolled neurological conditions, ongoing HIV, hepatitis B or C, active tuberculosis, recurrent infections, uncontrolled cardiac arrhythmias, or mental/emotional disorders that are not well controlled.
• Subject has diagnosed musculoskeletal cancer, or any other diagnosed cancer not on long term remission (e.g., at least 5 years or negative biopsy at last exam) except basal cell carcinoma.
• Subject who demonstrates any clinically significant abnormality for any of the following hematology testing within 30 days (± 2days) of enrollment: complete blood count with differential, blood chemistry \[comprehensive metabolic panel including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine, and CRP), coagulation profile (including international normalized ration (INR), prothrombin time (PT), activated partial thromboplastin time (APTT)\], Thrombin Time (TT) and, fibrinogen (FIB).
• Subject who demonstrates any clinically significant abnormality\* for any of the following vital signs within 30 days (± 2days) of enrollment, systolic BP \> 160 mmHg or \< 90 mmHg, pulse \> 100 bpm or \< 60 bpm, Respiratory Rate \> 25 or \< 10, O2 saturation \< 90% on Room Air.

Sponsors & Collaborators

• Johns Hopkins University: lead
• ON Foundation: collaborator

Study Sites (2)

Johns Hopkins Howard County General Hospital

Columbia, Maryland, 21230, United States

Location

Johns Hopkins Medicine - Green Spring Station

Lutherville, Maryland, 21093, United States

Location

Related Publications (10)

• Mather RC 3rd, Koenig L, Acevedo D, Dall TM, Gallo P, Romeo A, Tongue J, Williams G Jr. The societal and economic value of rotator cuff repair. J Bone Joint Surg Am. 2013 Nov 20;95(22):1993-2000. doi: 10.2106/JBJS.L.01495.

  PMID: 24257656 BACKGROUND

• Lawrence RL, Moutzouros V, Bey MJ. Asymptomatic Rotator Cuff Tears. JBJS Rev. 2019 Jun;7(6):e9. doi: 10.2106/JBJS.RVW.18.00149.

  PMID: 31246863 BACKGROUND

• Mandaleson A. Re-tears after rotator cuff repair: Current concepts review. J Clin Orthop Trauma. 2021 May 21;19:168-174. doi: 10.1016/j.jcot.2021.05.019. eCollection 2021 Aug.

  PMID: 34123722 BACKGROUND

• Narayanan G, Nair LS, Laurencin CT. Regenerative Engineering of the Rotator Cuff of the Shoulder. ACS Biomater Sci Eng. 2018 Mar 12;4(3):751-786. doi: 10.1021/acsbiomaterials.7b00631. Epub 2018 Feb 6.

  PMID: 33418763 BACKGROUND

• Vavken P, Sadoghi P, Palmer M, Rosso C, Mueller AM, Szoelloesy G, Valderrabano V. Platelet-Rich Plasma Reduces Retear Rates After Arthroscopic Repair of Small- and Medium-Sized Rotator Cuff Tears but Is Not Cost-Effective. Am J Sports Med. 2015 Dec;43(12):3071-6. doi: 10.1177/0363546515572777. Epub 2015 Mar 12.

  PMID: 25767267 BACKGROUND

• Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries. Front Bioeng Biotechnol. 2022 May 25;10:866195. doi: 10.3389/fbioe.2022.866195. eCollection 2022.

  PMID: 35694228 BACKGROUND

• Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.

  PMID: 24913770 BACKGROUND

• Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976). 1995 May 1;20(9):1055-60. doi: 10.1097/00007632-199505000-00012.

  PMID: 7631235 BACKGROUND

• Beitzel K, McCarthy MB, Cote MP, Durant TJ, Chowaniec DM, Solovyova O, Russell RP, Arciero RA, Mazzocca AD. Comparison of mesenchymal stem cells (osteoprogenitors) harvested from proximal humerus and distal femur during arthroscopic surgery. Arthroscopy. 2013 Feb;29(2):301-8. doi: 10.1016/j.arthro.2012.08.021. Epub 2013 Jan 3.

  PMID: 23290182 BACKGROUND

• You T, Wu S, Ou X, Liu Y, Wang X. A network meta-analysis of arthroscopic rotator cuff repair. BMC Surg. 2023 Jul 13;23(1):201. doi: 10.1186/s12893-023-02078-4.

  PMID: 37443010 BACKGROUND

MeSH Terms

Conditions

Rotator Cuff Injuries

Condition Hierarchy (Ancestors)

Rupture; Wounds and Injuries; Shoulder Injuries; Tendon Injuries

Study Officials

• Uma Srikumaran, MD, MBA, MPH

  Johns Hopkins University

  STUDY DIRECTOR

• Matthew J Best, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients and research assistants collecting data will be unaware of assigned treatment until study completion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is designed as a parallel group 1:1:1 randomized controlled trial.

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 12, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)