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

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

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.

Study Overview

• Status: Unknown
• Conditions: Brachial Plexus Injury
• Intervention / Treatment: Procedure: Mononuclear cell injection: 4 * 10e8 cells; Procedure: Mononuclear cell injection: 8 * 10e8 cells; Procedure: No mononuclear cell injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rob GHH Nelissen, MD, PhD; Phone Number: 0031715263606; Email: r.g.h.h.nelissen@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands, 2300RC
    • Recruiting
    • Leiden University Medical Center
    • Contact: Rob GHH Nelissen, MD, PhD; Phone Number: 0031715263606; Email: r.g.h.h.nelissen@lumc.nl
    • Contact: Bouke J Duijnisveld, MD, MSc; Phone Number: 0031715263606; Email: b.j.duijnisveld@lumc.nl
    • Principal Investigator: Rob GHH Nelissen, MD, PhD
    • Sub-Investigator: Bouke J Duijnisveld, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Procedure: Mononuclear cell injection: 4 * 10e8 cells; 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.
Experimental: B	Procedure: Mononuclear cell injection: 8 * 10e8 cells; 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.
No Intervention: C	Procedure: No mononuclear cell injection; Patients will receive a muscle tendon transposition surgery without bone marrow aspiration or mononuclear cell injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Rob GHH Nelissen, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Anticipated): January 1, 2011
• Study Completion (Anticipated): January 1, 2011

Study Registration Dates

• First Submitted: September 18, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Estimate): August 18, 2009
• Last Update Submitted That Met QC Criteria: August 17, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Fibrosis; Satellite cells; Stem cell transplantation; Brachial plexus; Muscle denervation; Bone marrow cells
• Other Study ID Numbers: 40-41200-98-040