- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03294720
BioACL Reconstruction With Amnion Collagen Matrix Wrap and Stem Cells Case Series (BioACL (CS))
April 6, 2021 updated by: Andrews Research & Education Foundation
Augmentation of ACL Reconstruction With Bone Marrow Stem Cells and Amnion Collagen Matrix Wrap: a Case Series
The objective of this study is to evaluate the use of wrapping an ACL graft with a collagen matrix tissue wrap and injecting autologous bone marrow aspirate concentrate under the wrapping and into the graft.
Investigators hypothesize that this method of augmenting ACL surgery will accelerate and improve the graft maturation and ligamentization process.
Investigators propose to test this hypothesis with a series of cases of ACL reconstructions evaluated with post-operative MRI mapping sequences and validated clinical outcome measures
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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) Investigators believe that use of a 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.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Gulf Breeze, Florida, United States, 32561
- Andrews Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 35 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients between the ages of 18 and 35 who are scheduled to have anterior cruciate ligament reconstruction with autologous grafts by the principal investigator 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bio ACL Reconstruction
Normal ACL reconstruction with either patellar or hamstring autograft will be done and prior to fixation the graft will be wrapped in a amion collagen wrap.
Bone marrow aspirate will be obtained from distal femur at the time of the arthroscopy and stem cells isolated using the Arthrex Angel System.
These stem cells with be under direct visualization impregnated into the ACL autograft amion wrap complex.
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ACL reconstruction with either hamstring or patellar autograft, wrapped in amion collagen wrap, and stem cells from bone marrow aspirate.
amnion collagen wrap and bone-marrow aspirate in ACL reconstruction autograft
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MRI graft maturation and integration
Time Frame: 3 months, 6 months, 9 months, and 12 months post-op
|
validated T2 star sequence which will undergo region of interest mapping to produce mean T2 values.
These values have been shown to detect differences in ACL content, structure and maturation.
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3 months, 6 months, 9 months, and 12 months post-op
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in patient-reported pain rating
Time Frame: 3 months, 6 months, 9 months, 12 months post-op
|
Visual analog scale will be used to assess pain
|
3 months, 6 months, 9 months, 12 months post-op
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Changes in Knee injury and Osteoarthritis Outcome Score (KOOS)
Time Frame: 3 months, 6 months, 9 months, 12 months post-op
|
Patients will complete KOOS questionnaire on SOS
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3 months, 6 months, 9 months, 12 months post-op
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Changes in Short Form 12 (SF-12) patient ratings
Time Frame: 3 months, 6 months, 9 months, 12 months post-op
|
Patients will complete SF-12 questionnaire on SOS
|
3 months, 6 months, 9 months, 12 months post-op
|
Changes in Single Assessment Numerical Evaluation (SANE) patient ratings for function
Time Frame: 3 months, 6 months, 9 months, 12 months post-op
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Patients will complete the SANE questionnaire on SOS
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3 months, 6 months, 9 months, 12 months post-op
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Marx Activity Scale Rating
Time Frame: 3 months, 6 months, 9 months, 12 months post-op
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Patients will complete the Marx Activity questionnaire on SOS
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3 months, 6 months, 9 months, 12 months post-op
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Adam Anz, MD, Andrews Insituite for Sports and Orthopaedics
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- Jang KM, Lim HC, Jung WY, Moon SW, Wang JH. Efficacy and Safety of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Anterior Cruciate Ligament Reconstruction of a Rabbit Model: New Strategy to Enhance Tendon Graft Healing. Arthroscopy. 2015 Aug;31(8):1530-9. doi: 10.1016/j.arthro.2015.02.023. Epub 2015 Apr 14.
- 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.
- 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.
- 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.
- 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.
- Li J, Wang J, Li Y, Shao D, You X, Shen Y. A Prospective Randomized Study of Anterior Cruciate Ligament Reconstruction With Autograft, gamma-Irradiated Allograft, and Hybrid Graft. Arthroscopy. 2015 Jul;31(7):1296-302. doi: 10.1016/j.arthro.2015.02.033. Epub 2015 Apr 17.
- 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.
- 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.
- Beitzel K, McCarthy MB, Cote MP, Chowaniec D, Falcone LM, Falcone JA, Dugdale EM, Deberardino TM, Arciero RA, Mazzocca AD. Rapid isolation of human stem cells (connective progenitor cells) from the distal femur during arthroscopic knee surgery. Arthroscopy. 2012 Jan;28(1):74-84. doi: 10.1016/j.arthro.2011.06.035. Epub 2011 Oct 11.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 8, 2018
Primary Completion (Anticipated)
December 31, 2021
Study Completion (Anticipated)
December 31, 2021
Study Registration Dates
First Submitted
September 20, 2017
First Submitted That Met QC Criteria
September 22, 2017
First Posted (Actual)
September 27, 2017
Study Record Updates
Last Update Posted (Actual)
April 8, 2021
Last Update Submitted That Met QC Criteria
April 6, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BioACL (CS)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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