Bio ACL Reconstruction Amnion Collagen Matrix Wrap and Stem Cells

ACL - Anterior Cruciate Ligament Rupture Clinical Trial

— BioACLRCT  

Official title:

Pilot Study: Augmentation of ACL Reconstruction With Bone Marrow Stem Cells and Amnion Collagen Matrix Wrap

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03294759
• Other study ID #: Bio ACL (RCT)
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 6, 2017
• Est. completion date: December 6, 2024

Study information

• Verified date: February 2024
• Source: Andrews Research & Education Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Collagen based -membrane derived from amniotic tissue can be used to help reestablish the natural synovial lining of the reconstructed ACL, in effect acting as both a barrier from the synovial fluid and as a scaffold to contain autologous mesenchymal stem cells and growth factors contiguous with the graft, thus aiding and perhaps accelerating the natural maturation and ligamentization process of the implanted graft tissue. Acceleration and improvement in graft maturation and strength would be a significant advancement in sports medicine allowing safer and earlier return to sports and activity

Description:

Histologic studies have determined that graft ligamentization following anterior cruciate ligament (ACL) reconstruction may take from 6 to 18 months. (1) It has been reported that incomplete graft maturation and incorporation is one cause of clinical graft failure. Animal studies have illustrated improved tendon healing/integration in ACL models augmented with stem cell technologies. (2-4). Basic scientists theorize that optimization of stem cell treatments for tissue regeneration requires that a "regenerative triad" be employed, i.e., use of a scaffold, stem cells and growth factors. In the intra-articular environment, research has shown that a scaffold such as an amnion wrap is necessary to contain the stem cells and growth factors in close proximity to the ACL graft. (2, 4, 5)

The normal, uninjured human ACL is covered by a layer of synovial tissue which contributes to the blood supply and nutrition of the native ACL. It is theorized that the lack of a synovial lining after injury and following traditional ACL reconstruction contributes to slow ligamentization and possible failure of reconstructed grafts.(5) Two studies have demonstrated accelerated maturation and ligamentization of human ACL graft augmented with point of care blood products. (6, 7) In one, leucocyte poor platelet rich plasma was injected directly into the body of the graft. (6) In the other, the platelet derived growth factors were loaded in a gelatin carrier which was wrapped around the graft. (7) In both studies accelerated and increased ligament maturation was documented compared to the controls. Collagen membranes derived from amniotic tissue have been successful to aid healing when used in difficult wounds and meniscal repair surgery. (8, 9)

The use of a collagen based -membrane derived from amniotic tissue may be used to help reestablish the natural synovial lining of the reconstructed ACL, in effect acting as both a barrier from the synovial fluid and as a scaffold to contain autologous mesenchymal stem cells and growth factors contiguous with the graft. Thus aiding and perhaps accelerating the natural maturation and ligamentization process of the implanted graft tissue. Acceleration and improvement in graft maturation and strength would be a significant advancement in sports medicine allowing safer and earlier return to sports and activity.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 6, 2024
• Est. primary completion date: December 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Patients between the ages of 18 and 45 who are scheduled to have anterior cruciate ligament reconstruction with autologous grafts by one of the investigating physicians will be screened for participation in this study.

• Patients must be willing to undergo MRI scans post -operatively at 3, 6, 9 months and 1 year

Exclusion Criteria:

• Patients with prior procedures or significant prior injuries to the same knee are excluded. - - Any patient who will have difficulty obtaining internet access, does not have an active e-mail address, or is unable to comprehend study documents or give informed consent will be excluded.

• Patient who are unable to complete MRI examinations due to claustrophobia or anxiety will be excluded.

Related Conditions & MeSH terms

• ACL - Anterior Cruciate Ligament Rupture
• Rupture

Intervention

Other:
• Bio ACL
Bone marrow aspirate will be centrifuged using the Arthrex Angel system to optimally concentrate the cells for implantation. The graft for the experimental groups will be wrapped with a sterile amnion matrix wrap, supplied by Arthrex
• Control
Normal ACL reconstruction technique with either patella or hamstring autograft

Locations

Country	Name	City	State
United States	Andrews Institute	Gulf Breeze	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Andrews Research & Education Foundation	Arthrex, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (12)

Baeten D, Van den Bosch F, Elewaut D, Stuer A, Veys EM, De Keyser F. Needle arthroscopy of the knee with synovial biopsy sampling: technical experience in 150 patients. Clin Rheumatol. 1999;18(6):434-41. doi: 10.1007/s100670050134. — View Citation

Biercevicz AM, Akelman MR, Fadale PD, Hulstyn MJ, Shalvoy RM, Badger GJ, Tung GA, Oksendahl HL, Fleming BC. MRI volume and signal intensity of ACL graft predict clinical, functional, and patient-oriented outcome measures after ACL reconstruction. Am J Sports Med. 2015 Mar;43(3):693-9. doi: 10.1177/0363546514561435. Epub 2014 Dec 24. — View Citation

Claes S, Verdonk P, Forsyth R, Bellemans J. The "ligamentization" process in anterior cruciate ligament reconstruction: what happens to the human graft? A systematic review of the literature. Am J Sports Med. 2011 Nov;39(11):2476-83. doi: 10.1177/0363546511402662. Epub 2011 Apr 22. — View Citation

DiDomenico LA, Orgill DP, Galiano RD, Serena TE, Carter MJ, Kaufman JP, Young NJ, Zelen CM. Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial. Plast Reconstr Surg Glob Open. 2016 Oct 12;4(10):e1095. doi: 10.1097/GOX.0000000000001095. eCollection 2016 Oct. — View Citation

Joshi SM, Mastrangelo AN, Magarian EM, Fleming BC, Murray MM. Collagen-platelet composite enhances biomechanical and histologic healing of the porcine anterior cruciate ligament. Am J Sports Med. 2009 Dec;37(12):2401-10. doi: 10.1177/0363546509339915. — View Citation

Li H, Tao H, Cho S, Chen S, Yao Z, Chen S. Difference in graft maturity of the reconstructed anterior cruciate ligament 2 years postoperatively: a comparison between autografts and allografts in young men using clinical and 3.0-T magnetic resonance imaging evaluation. Am J Sports Med. 2012 Jul;40(7):1519-26. doi: 10.1177/0363546512443050. Epub 2012 Apr 11. — View Citation

Matsumoto T, Kubo S, Sasaki K, Kawakami Y, Oka S, Sasaki H, Takayama K, Tei K, Matsushita T, Mifune Y, Kurosaka M, Kuroda R. Acceleration of tendon-bone healing of anterior cruciate ligament graft using autologous ruptured tissue. Am J Sports Med. 2012 Jun;40(6):1296-302. doi: 10.1177/0363546512439026. Epub 2012 Mar 16. — View Citation

Mifune Y, Matsumoto T, Takayama K, Terada S, Sekiya N, Kuroda R, Kurosaka M, Fu FH, Huard J. Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction. Biomaterials. 2013 Jul;34(22):5476-87. doi: 10.1016/j.biomaterials.2013.04.013. Epub 2013 Apr 28. — View Citation

Piontek T, Ciemniewska-Gorzela K, Naczk J, Jakob R, Szulc A, Grygorowicz M, Slomczykowski M. Complex Meniscus Tears Treated with Collagen Matrix Wrapping and Bone Marrow Blood Injection: A 2-Year Clinical Follow-Up. Cartilage. 2016 Apr;7(2):123-39. doi: 10.1177/1947603515608988. Epub 2015 Nov 30. — View Citation

Radice F, Yanez R, Gutierrez V, Rosales J, Pinedo M, Coda S. Comparison of magnetic resonance imaging findings in anterior cruciate ligament grafts with and without autologous platelet-derived growth factors. Arthroscopy. 2010 Jan;26(1):50-7. doi: 10.1016/j.arthro.2009.06.030. — View Citation

Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications. Am J Sports Med. 2016 Sep;44(9):2425-34. doi: 10.1177/0363546515612750. Epub 2015 Nov 19. — View Citation

Sanchez M, Anitua E, Azofra J, Prado R, Muruzabal F, Andia I. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy. 2010 Apr;26(4):470-80. doi: 10.1016/j.arthro.2009.08.019. Epub 2010 Jan 15. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in ACL	MRI region of interest mapping to produce mean T2 values	3 months, 6 months, 9 months, 12 months post-op
Secondary	Changes in patient-reported pain rating	Visual analog scale will be used to assess pain	3 months, 6 months, 9 months, 12 months post-op
Secondary	Changes in Knee injury and Osteoarthritis Outcome Score (KOOS)	Patients will complete KOOS questionnaire on SOS	3 months, 6 months, 9 months, 12 months post-op
Secondary	Changes in Short Form 12 (SF-12) patient ratings	Patients will complete SF-12 questionnaire on SOS	3 months, 6 months, 9 months, 12 months post-op
Secondary	Changes in Single Assessment Numerical Evaluation (SANE) patient ratings for function	Patients will complete the SANE questionnaire on SOS	3 months, 6 months, 9 months, 12 months post-op
Secondary	Marx Activity Scale Rating	Patients will complete the Marx Activity questionnaire on SOS	12 months post-op