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BMAC Nerve Allograft Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03964129
Recruitment Status : Unknown
Verified July 2020 by Julia AV Nuelle, Brooke Army Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : May 28, 2019
Last Update Posted : July 16, 2020
Sponsor:
Collaborators:
Walter Reed National Military Medical Center
Curtis National Hand Center at MedStar Union Memorial Hospital
Cleveland Clinic Lerner Research Institute
Information provided by (Responsible Party):
Julia AV Nuelle, Brooke Army Medical Center

Study Description
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Brief Summary:
This study is a prospective, multi-center, proof of principle, phase I human safety study evaluating the sequential treatments of the Avance Nerve Graft, a commercially available decellularized processed peripheral nerve allograft, with autologous Bone Marrow Aspirate Concentrate (BMAC), a source of stem cells, for the repair of peripheral nerve injuries up to 7 cm in length. The purpose of this study is to establish a knowledge product, evaluating the safety profile of the Avance Nerve Graft, followed by the application of BMAC to support further investment into the promising area of using stem cells in conjunction with scaffolds.

Condition or disease Intervention/treatment Phase
Peripheral Nerve Injury Upper Limb Procedure: Avance Nerve Graft with Autologous BMAC Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Aspirate Concentrate (BMAC) to Improve Peripheral Nerve Repair and Functional Outcomes
Actual Study Start Date : August 22, 2017
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Avance Nerve Graft with autologous BMAC
The Avance Nerve Graft will be inserted in the area of nerve injury. Between 40 to 60 ml of Bone Marrow Aspirate from the anterior or posterior iliac crest of the pelvis will be harvested . Using SmartPrep centrifuge and 60 ml BMAC kit, 7 to 10 ml of final BMAC will be obtained.
 Procedure: Avance Nerve Graft with Autologous BMAC
The Avance Nerve Graft will be inserted in the area of nerve injury. Between 40 to 60 ml of Bone Marrow Aspirate from the anterior or posterior iliac crest of the pelvis will be harvested. Using SmartPrep centrifuge and 60 ml BMAC kit, 7 to 10 ml of final BMAC will be obtained. Of the 7 to 10 ml of final BMAC that is yielded, half (3.5 to 5 ml) of the final concentrate, will be injected on top of the Avance Nerve Graft following coaptation. The second half (3.5 to 5 ml) of the final concentrate will be inserted into a sterile tube containing culture media and shipped overnight to Cleveland Clinic Lerner Research Institute for cell processing and colony assay to confirm that the BMAC indeed contains autologous bone marrow stem cells.


Outcome Measures
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Primary Outcome Measures :
  1. Comparison of the nature and incidence of AEs between the group of subjects receiving Avance Nerve Graft with BMAC and the historical data of nerve repairs with the Avance Nerve Graft. [ Time Frame: 18 months ]
    Long-term study associated AEs, such as infection, wound dehiscence, neuropathy, carpal tunnel syndrome, bleeding, seroma, and lymphocele will be captured and analyzed together with any change in incidence of listed AEs which may be precipitated by treatment. . AEs will be mapped to a MedDRA preferred term and system organ classification. The occurrence of the AEs will be summarized by repair type using MedDRA preferred terms, system organ classifications, and severity. All AEs will be listed for individual subjects showing both verbatim and preferred terms. Separate summaries of treatment-emergent SAEs and AEs related to repair will be generated.


Secondary Outcome Measures :
  1. Test of non-inferiority and superiority of Avance Nerve Graft to historical nerve autograft scores with respect to Rosen-Lundborg using closed testing procedures [ Time Frame: 18 months ]

    Test of non-inferiority and superiority of Avance Nerve Graft to historical nerve autograft scores with respect to Rosen-Lundborg will be conducted using closed testing procedures. The hypotheses being tested are as follows:

    H01: Δ ≤ -Δ0 vs. H11: Δ > -Δ0 H02: Δ = 0 vs. H12: Δ ≠ 0 where Δ = μC- μA is the difference between the mean Rosen-Lundborg Scores for the Avance Nerve Graft & BMAC (μA) and the mean Rosen-Lundborg scores for the historical autograft controls (μC), Δ0 is the non-inferiority margin 0.51. The null hypothesis of non-inferiority (H01) will be tested first and, if rejected, then the null hypothesis of superiority (H02) will be assessed. Given that the closed testing procedure is implemented, no adjustment for multiple testing will be required.


  2. Test of non-inferiority of Avance Nerve Graft plus BMAC to Avance Nerve Graft recovery rates with respect to Rosen-Lundborg scores using closed testing procedures [ Time Frame: 18 months ]

    Test of non-inferiority of Avance Nerve Graft plus BMAC to Avance Nerve Graft recovery rates with respect to Rosen-Lundborg scores will be conducted using closed testing procedures. The hypothesis being tested is as follows:

    H01: πA - πAB > Δ vs. H11: πA - πAB < Δ where πA is the recovery of Avance Nerve Graft and πAB is the recovery of Avance plus BMAC. Δ is the non-inferiority margin 25%



Other Outcome Measures:
  1. Comparison of Motor Percent Recovery to Baseline Range of Motion [ Time Frame: 18 months ]
    Percent of motor recovery to baseline (defined as the difference in the measured assessment of the repaired nerve as compared with neighboring uninjured and/or contra-lateral side) based on passive range of motion, active range of motion and muscle strength (M0-M5) measurements

  2. Comparison of Motor Percent Recovery to Baseline Grip Strength [ Time Frame: 18 months ]
    Percent of grip strength recovery to baseline (defined as the difference in the measured assessment of the repaired nerve as compared with neighboring uninjured and/or contra-lateral side) measured in kilograms using the Neurosensory & Motor Testing System AcroGrip Device

  3. Comparison of Motor Percent Recovery to Baseline Pinch Strength [ Time Frame: 18 months ]
    Percent of pinch strength recovery to baseline (defined as the difference in the measured assessment of the repaired nerve as compared with neighboring uninjured and/or contra-lateral side) measured in kilograms using the Neurosensory & Motor Testing System AcroPinch Device

  4. Time to Recovery [ Time Frame: 18 months ]
  5. Functional Outcomes through the assessment of Quick Disabilities of the Arm Shoulder and Hand (QuickDASH) questionnaire [ Time Frame: 18 months ]
    QuickDASH Disability/Symptom, Work Module, and Sports/Performing Arts Module Raw Score (out of 5) and Final Score (out of 100) will be recorded. Raw Scores will be calculated by: Raw Score = sum of n responses/n, where n is equal to number of completed items.The Final Score (out of 100) scaled from 0 indicating least disability to 100 indicating most disability will be calculated by: Final score = (Raw Score - 1) X 25

  6. Functional Outcomes through the assessment of Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: 18 months ]
    Raw and Standardized scores for Physical Function, Pain Intensity, Pain Interference, Fatigue, Sleep Disturbance and Behavior assessments will be recorded. Raw Scores will be calculated by: (Raw Sum X number of items listed in the domain)/Number of items that were actually answered for each assessment. The Raw Score is then systematically transformed to a standardized T-score using a conversion table in the PROMIS Scoring Manual. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. The higher the T-score, the more it represents the concept being measured

  7. Motor and Sensory Nerve Conduction Studies (Nerve Conduction Velocity (NCV) and/or Electromyography (EMG)) [ Time Frame: 12 and 18 month ]

    NCV and EMG testing will be conducted on the target muscle group to assess rate and level of motor and sensory reinnervation in the 12 month and 18 month

    • Rate of Reinnervation (Motor and Sensory Domain)
    • Level of Reinnervation (Motor and Sensory Domain)

  8. Comparison of Sensory Percent Recovery to Baseline [ Time Frame: 18 months ]
    Percent of sensory recovery to baseline (defined as the difference in the measured assessment of the repaired nerve as compared with neighboring uninjured and/or contra-lateral side) using the Neurosensory & Motor Testing System (NSMTS) Pressure Specified Sensory Device. 1 Point Static Discrimination, 1 Point Static Moving Discrimination, 2 Point Static Discrimination and 2 Point Moving Discrimination will be measured by prong pressure (g/mm^2)


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or non-pregnant female 18 to 74 years of age.
  • Undergoing peripheral nerve exploration or grafting with allograft in the upper extremity.
  • Subjects must be inpatients or scheduled for surgery at the time of study enrollment.
  • Has nerve conduction block injuries to the ulnar, median, radial or musculocutaneous nerve of either upper extremities that is less than two years from injury.
  • Be willing to undergo tension free end-to-end nerve graft coaptation on both the proximal and distal portion of the nerve gap with the Avance Nerve Graft.
  • Be willing to have bone marrow harvested from own body, concentrated, and applied to the site of nerve injury following the insertion of the Avance Nerve Graft.
  • Be willing to participate and able to comply with all aspects of the treatment and evaluation schedule over a 18-month duration.
  • Capable of giving their own consent to participate in the study, and willing to sign and date an IRB-approved written informed consent prior to initiation of any study procedures.
  • Nerve conduction injury affecting sensory and motor function or solely motor function in the upper extremity.
  • Nerve gaps following resection, up to 7 cm, inclusive.

Exclusion Criteria:

  • Subjects with Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus requiring regular insulin therapy.
  • Subjects who are undergoing or expected to undergo treatment with chemotherapy, radiation therapy, or other known treatment which affects the growth of neural and/or vascular system.
  • History of neurodegenerative disease, neuropathy, or diabetic neuropathy.
  • History of chronic ischemic condition of the upper extremity.
  • Cognitive limitation or mental illness preventing informed consent.
  • Nerve injuries >2 years post initial injury.
  • Any participant who at the discretion of the Investigator is not suitable for inclusion in the study.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03964129


Locations
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United States, Maryland
Curtis National Hand Center at MedStar Union Memorial Hospital
Baltimore, Maryland, United States, 21218
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889
United States, Texas
San Antonio Military Medical Center
Fort Sam Houston, Texas, United States, 78234
Sponsors and Collaborators
Brooke Army Medical Center
Walter Reed National Military Medical Center
Curtis National Hand Center at MedStar Union Memorial Hospital
Cleveland Clinic Lerner Research Institute
Investigators
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Principal Investigator: Julia Nuelle, MD Brooke Army Medical Center
Principal Investigator: Leon J Nesti, MD/PhD Walter Reed National Military Medical Center
Principal Investigator: Kenneth Means, MD Curtis Hand Center at MedStar Union Memorial Hospital
  Study Documents (Full-Text)

Documents provided by Julia AV Nuelle, Brooke Army Medical Center:
Study Protocol and Statistical Analysis Plan  [PDF] August 27, 2018

More Information
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Publications:
Brushart, T.M. (2011). Nerve Repair (Oxford University Press).
Center for Biologics Evaluation and Research, C. for D. and R.H. Cellular & Gene Therapy Guidances - Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products: Draft Guidance.
Frykman, G., and Gramyk, K. (1991). Results of Nerve Grafting In: Gelberman R. Operative nerve repair and reconstruction. (JB Lippincott).
Graham, James B., Xue, Qing-Shan, Neubauer, Debbie, and Muir, David (2009). A chondroitinase-treated, decellularized nerve allograft compares favorably to the cellular isograft in rat peripheral nerve repair. 2, 19-29
Kragh, Kirby, J.M., and Ficke, J.R. Combat casualty care : lessons learned from OEF and OIF. Chapter 9: Extremity Injury. (2012) Editor-in-chief, Martha K. Lenhart; medical editor, Eric Savitsky; military editor, Brian Eastridge. Pgs. 393-484
PRWeb. (2015). AxoGen Inc.'s Avance Nerve Graft Data Presented During Bese Clinical Papers Session at the 70th Annual Meeting of the American Society for Surgery of the Hand. Vocus, Inc. Sep. 10, 2015

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Responsible Party: Julia AV Nuelle, Orthopaedic Hand and Microvascular Surgeon, Brooke Army Medical Center
ClinicalTrials.gov Identifier: NCT03964129    
Other Study ID Numbers: C.2017.074
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peripheral Nerve Injuries
Peripheral Nervous System Diseases
Neuromuscular Diseases
 Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries