Clinical trial NCT03294759: Bio ACL Reconstruction Amnion Collagen Matrix Wrap and Stem Cells
Official title: Pilot Study: Augmentation of ACL Reconstruction With Bone Marrow Stem Cells and Amnion Collagen Matrix Wrap
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: ACL - Anterior Cruciate Ligament Rupture
Keywords: amion
stem cell
acl
Lead sponsor: Andrews Research & Education Foundation
Sponsor class: OTHER
Collaborators: name: Arthrex, Inc.
First posted: 2017-09-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: ACL harvested for autograft reconstruction of the ACL with either hamstring or patellar tendon grafts. The graft will be wrapped in a collagen wrap and injection with aspirate from the patient's bone marrow.

The control group will have standard ACL reconstruction with either hamstring or patellar tendon grafts.
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in ACL
timeFrame: 3 months, 6 months, 9 months, 12 months post-op
Secondary outcomes:
measure: Changes in patient-reported pain rating
timeFrame: 3 months, 6 months, 9 months, 12 months post-op
measure: Changes in Knee injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 3 months, 6 months, 9 months, 12 months post-op
measure: Changes in Short Form 12 (SF-12) patient ratings
timeFrame: 3 months, 6 months, 9 months, 12 months post-op
measure: Changes in Single Assessment Numerical Evaluation (SANE) patient ratings for function
timeFrame: 3 months, 6 months, 9 months, 12 months post-op
measure: Marx Activity Scale Rating
timeFrame: 12 months post-op
Other outcomes:
Locations:
city: Gulf Breeze
country: United States
facility: Andrews Institute
state: Florida
Study officials:
affiliation: Andrews Research & Education Foundation
name: Adam Anz, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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