BMAC Nerve Allograft Study

Sponsor

Brooke Army Medical Center (U.S. Fed)

Overall Status

Unknown status

CT.gov ID

NCT03964129

Collaborator

Walter Reed National Military Medical Center (U.S. Fed), Curtis National Hand Center at MedStar Union Memorial Hospital (Other), Cleveland Clinic Lerner Research Institute (Other)

Enrollment

Locations

Arm

45.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	N/A

Study Design

Study Type:

Interventional

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 :

Aug 22, 2017

Anticipated Primary Completion Date :

Nov 30, 2020

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

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.

Arm

Intervention/Treatment

Experimental: Avance Nerve Graft with autologous BMAC

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

Primary Outcome Measures

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. [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

Test of non-inferiority and superiority of Avance Nerve Graft to historical nerve autograft scores with respect to Rosen-Lundborg using closed testing procedures [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.
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 [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

Comparison of Motor Percent Recovery to Baseline Range of Motion [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
Comparison of Motor Percent Recovery to Baseline Grip Strength [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
Comparison of Motor Percent Recovery to Baseline Pinch Strength [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
Time to Recovery [18 months]
Functional Outcomes through the assessment of Quick Disabilities of the Arm Shoulder and Hand (QuickDASH) questionnaire [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
Functional Outcomes through the assessment of Patient-Reported Outcomes Measurement Information System (PROMIS) [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
Motor and Sensory Nerve Conduction Studies (Nerve Conduction Velocity (NCV) and/or Electromyography (EMG)) [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)
Comparison of Sensory Percent Recovery to Baseline [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

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Curtis National Hand Center at MedStar Union Memorial Hospital	Baltimore	Maryland	United States	21218
2	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889
3	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

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)

Study Protocol and Statistical Analysis Plan - Aug 27, 2018

More Information

Publications

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

Last Update Posted:

Jul 16, 2020

Last Verified:

Jul 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Peripheral Nerve Injuries

Study Results

No Results Posted as of Jul 16, 2020