Development of Novel Strategy for Treatment of Anterior Cruciate Ligament (ACL) Injury Using Stem Cell

A Randomized, Single Center, Investigator Initiated Clinical Trial to Evaluate Enhancement of Healing Between Bone Tunnel and Graft in Anterior Cruciate Ligament (ACL) Injury Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cell

Purpose:Development of novel strategy for treatment of anterior cruciate ligament (ACL) injury using stem cell.

Study Overview

• Status: Completed
• Conditions: Deficiency of Anterior Cruciate Ligament
• Intervention / Treatment: Procedure: ACL reconstruction only; Biological: Cartistem(TM); Biological: hyaluronic acid

Detailed Description

1. Purpose: Development of novel strategy for treatment of anterior cruciate ligament (ACL) injury using stem cell.

2. Subject: Anterior cruciate ligament (ACL) injury 30 patients

   • ACL reconstruction: 10
   • ACL reconstruction + Human cord blood derived mesenchymal stem cells and hyaluronic acid (Cartistem (TM)): 10
   • ACL reconstruction + hyaluronic acid: 10
3. Hypothesis: Human Cord blood derived mesenchymal stem cells can enhance healing between bone tunnel and graft in ACL reconstruction.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 20~50
2. Lachman test grade II,III or Pivot shift test grade I,II,III or ACL rupture in MRI
3. prothrombin time (PT) (INR) <1.5, activated partial thromboplastin time (aPTT) <1.5 x control
4. Creatinine ≤2.0 ㎎/㎗, protein uria(dipstick) ≤ trace
5. Bilirubin ≤2.0 ㎎/㎗, aspartate aminotransferase (AST) /Alanine Aminotransferase (ALT) ≤100 IU/L
6. No surgery and radiation therapy in recent 6 weeks
7. No pregnancy
8. No combine ligament instability ≥ grade II in physical examination (grade 0: none, grade I: 0~5mm, grade II: 5~10mm, grade III: >10mm)
9. voluntary singed a consent form

Exclusion Criteria:

1. Degenerative osteoarthritis in knee
2. Revision or other surgery history (stem cell treatment)
3. Chronic inflammatory joint disease like rheumatoid arthritis
4. Infectious disease need to administration of parenteral antibiotics
5. Autoimmune disease
6. Myocardial infarction, congestive heart failure, other serious heart disease
7. Uncontrolled hypertension
8. Serious medical disease
9. Pregnancy and breast-feeding
10. psychiatric disorder and epilepsy
11. Alcohol overuse
12. Smoking overuse
13. Administration of immunosuppressive agents like Cyclosporin A or Azathioprine in recent 6 weeks prior screening test
14. Patient participating in other clinical trials in recent 4 weeks
15. Combined ligament instability ≥ grade II in physical test.
16. No allergy history to gentamicin antibiotics
17. Hypersensitivity patient to bovine protein, hyaluronic acid, and anesthetic agent
18. Inappropriate patient judged by researcher.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACL reconstruction only; only ACL reconstruction without any injection	Procedure: ACL reconstruction only; ACL reconstruction only without any injection under arthroscopy
Experimental: ACL reconstruction + Cartistem(TM); ACL reconstruction and concomitant Cartistem(TM) injection which is human cord blood derived mesenchymal stem cell under arthroscopy.	Procedure: ACL reconstruction only; ACL reconstruction only without any injection under arthroscopy; Biological: Cartistem(TM); ACL reconstruction and injection of Cartstem(TM), human cord blood derived mesenchymal stem cell under arthroscopy.
Experimental: ACL reconstruction + Hyaluronic acid; ACL reconstruction and concomitant hyaluronic acid injection under arthroscopy	Procedure: ACL reconstruction only; ACL reconstruction only without any injection under arthroscopy; Biological: hyaluronic acid; ACL reconstruction and injection of hyaluronic acid under arthroscopy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone formation on interface between bone tunnel and graft	Changes at 12 week, 24 week, 48 week after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Arthroscopic grading of graft	48 week after surgery
Telos stress X-ray	Changes at 12 week, 24 week, 48 week after surgery
KT-2000	Changes at 12 week, 24 week, 48 week after surgery
clinical knee scoring	Changes at 12 week, 24 week, 48 week after surgery
Instability assessing with physical examination	Changes at 12 week, 24 week, 48 week after surgery
Tunnel enlargement after anterior cruciate ligament reconstruction	Changes at 12 week, 24 week, 48 week after surgery

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Study Chair: Joon Ho Wang, MD, Ph D, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): April 28, 2016
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: February 22, 2015
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: SMC 2013-07-117-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: age, physical exam, lab, etc will be shared