免费获得国外相关药品，最快 1 个工作日回馈药物信息
出境医 / 临床实验 / BMAC Nerve Allograft Study
BMAC Nerve Allograft Study
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 | Not Applicable |
Study Design
| 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 |
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.
|
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. [ 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 :
- 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.
- 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:
- 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
- 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
- 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
- Time to Recovery [ Time Frame: 18 months ]
- 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
- 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
- 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)
- 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
| 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
Locations
| 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
| 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 |
| Tracking Information | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 20, 2019 | |||||||||
| First Posted Date ICMJE | May 28, 2019 | |||||||||
| Last Update Posted Date | July 16, 2020 | |||||||||
| Actual Study Start Date ICMJE | August 22, 2017 | |||||||||
| Estimated Primary Completion Date | November 30, 2020 (Final data collection date for primary outcome measure) | |||||||||
| Current Primary Outcome Measures ICMJE |
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.
|
|||||||||
| Original Primary Outcome Measures ICMJE | Same as current | |||||||||
| Change History | ||||||||||
| Current Secondary Outcome Measures ICMJE |
|
|||||||||
| Original Secondary Outcome Measures ICMJE | Same as current | |||||||||
| Current Other Pre-specified Outcome Measures |
|
|||||||||
| Original Other Pre-specified Outcome Measures | Same as current | |||||||||
| Descriptive Information | ||||||||||
| Brief Title ICMJE | BMAC Nerve Allograft Study | |||||||||
| Official Title ICMJE | Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Aspirate Concentrate (BMAC) to Improve Peripheral Nerve Repair and Functional Outcomes | |||||||||
| 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. | |||||||||
| Detailed Description | Not Provided | |||||||||
| Study Type ICMJE | Interventional | |||||||||
| Study Phase ICMJE | Not Applicable | |||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
|||||||||
| Condition ICMJE | Peripheral Nerve Injury Upper Limb | |||||||||
| Intervention ICMJE | 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.
|
|||||||||
| Study Arms ICMJE | 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.
Intervention: Procedure: Avance Nerve Graft with Autologous BMAC
|
|||||||||
| Publications * |
|
|||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
||||||||||
| Recruitment Information | ||||||||||
| Recruitment Status ICMJE | Active, not recruiting | |||||||||
| Actual Enrollment ICMJE |
15 | |||||||||
| Original Estimated Enrollment ICMJE |
45 | |||||||||
| Estimated Study Completion Date ICMJE | June 1, 2021 | |||||||||
| Estimated Primary Completion Date | November 30, 2020 (Final data collection date for primary outcome measure) | |||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
|||||||||
| Sex/Gender ICMJE |
|
|||||||||
| Ages ICMJE | 18 Years to 74 Years (Adult, Older Adult) | |||||||||
| Accepts Healthy Volunteers ICMJE | No | |||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||||||||
| Listed Location Countries ICMJE | United States | |||||||||
| Removed Location Countries | ||||||||||
| Administrative Information | ||||||||||
| NCT Number ICMJE | NCT03964129 | |||||||||
| Other Study ID Numbers ICMJE | C.2017.074 | |||||||||
| Has Data Monitoring Committee | Not Provided | |||||||||
| U.S. FDA-regulated Product |
|
|||||||||
| IPD Sharing Statement ICMJE | Not Provided | |||||||||
| Responsible Party | Julia AV Nuelle, Brooke Army Medical Center | |||||||||
| Study Sponsor ICMJE | Brooke Army Medical Center | |||||||||
| Collaborators ICMJE |
|
|||||||||
| Investigators ICMJE |
|
|||||||||
| PRS Account | Brooke Army Medical Center | |||||||||
| Verification Date | July 2020 | |||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
||||||||||
