Stem Cell Therapy to Improve the Muscle Function of Patients With Partly Denervated Muscles of the Arm

Study Overview
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Brief Summary
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The purpose of this study is to assess muscle improvement after stem cell injection in the biceps muscle of patients with a brachial plexus injury.

Detailed Description
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Brachial plexus injuries can cause severe disabilities and often affect young adults and newborn children. When initial conservative treatment or nerve surgery fails, muscle/tendon transfers are the only current treatment options available to regain a functional arm. During this extensive surgery a healthy donor muscle is transposed to exert a different function. After long-term denervation the muscle is irreversibly changed. Muscle atrophy, fattening, fibrosis, decrease in capillary to muscle fiber ratio and decline in the number of satellite cells, which are responsible for post-natal muscle repair, is seen. For neuromuscular diseases, cell therapy aiming at rescuing muscle damage by delivery of cells that can differentiate into skeletal muscle, might be a promising approach. Safety questions remain whether stem cell injection results in non-muscle tissue formation like inflammatory cells or connective tissue formation in the transplanted muscles. Furthermore, it remains to be determined whether these stem cells undergo functional integration and enhance muscle function. The objective of this pilot study is to assess functional and morphological improvement of the m. biceps brachii after autologous bone marrow-derived mononuclear cell injection.

Official Title
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Autologous Bone Marrow Transplantation for Muscle Improvement in Traumatic Brachial Plexus Injuries

Conditions
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Brachial Plexus Injury

Intervention / Treatment
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* Procedure: Mononuclear cell injection: 4 * 10e8 cells
* Procedure: Mononuclear cell injection: 8 * 10e8 cells
* Procedure: No mononuclear cell injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BP patients with paresis of m. biceps brachii (MRC 1,2,3), either after conservative treatment or at least two years after nerve surgery with partial recovery of the elbow flexor Patients capable and willing to give informed consent Exclusion Criteria: Function recovery of the elbow flexor (m. biceps brachii) to a MRC motor scale of 0 EMG activity: no motor unit potentials Medical history of other central of peripheral neurological disorders Inability to undergo BM harvesting Bleeding diathesis, INR > 2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Procedure: Mononuclear cell injection: 4 * 10e8 cells<br>* 350 ml bone marrow will be aspirated from the posterior iliac crest under general anesthesia in combination with a muscle tendon transposition surgery. Next, the patients will receive a bone marrow derived mononuclear cell injection of 4 * 10e8 cells in the m. biceps brachii.<br>|
| Experimental: B<br> | Procedure: Mononuclear cell injection: 8 * 10e8 cells<br>* 650 ml bone marrow will be aspirated from the posterior iliac crest under general anesthesia in combination with a muscle tendon transposition surgery. Next, the patients will receive a bone marrow derived mononuclear cell injection of 8 * 10e8 cells in the m. biceps brachii.<br>|
| No Intervention: C<br> | Procedure: No mononuclear cell injection<br>* Patients will receive a muscle tendon transposition surgery without bone marrow aspiration or mononuclear cell injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess muscle improvement, muscle biopsies, quantitative needle EMGs, muscle density analysis, force measurement, range of motion of the elbow joint and quality of life questionnaires will be performed. |  | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary research aim of this study is to assess vital signs and to detect signs of hematoma and/or injection at the bone marrow aspiration site, injection site and/or surgical wound. |  | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brachial plexus, Muscle denervation, Stem cell transplantation, Bone marrow cells, Satellite cells, Fibrosis