Exercise Training for Brachial Plexus Injury Following Nerve Transfer

Exercise Training to Improve Nerve Regeneration and Function in Patients With Brachial Plexus Injury Following Nerve Transfer - a Randomized Controlled Clinical Trial

Although peripheral nerve is capable of regrowth following injury, at only 1 mm/day, the slow rate represents a major barrier. Apart from rapid deterioration of the environment supportive of growth, denervated muscles become atrophic and bones osteoporotic. To successfully restore function, in addition to speeding up the nerve regeneration rate, treatments that can also restore muscle and bone mass are essential. Recently, in animal studies, the investigators showed that in addition to accelerating the speed of nerve regeneration, exercise training can also be used to restore muscle bulk and bone density. While promising, given the inter-species differences, the clinical utilities of this treatment need to be directly tested in humans. This will be done using a randomized controlled study design on patients with brachial plexus injury.

Study Overview

• Status: Not yet recruiting
• Conditions: Brachial Plexus Injury
• Intervention / Treatment: Other: Exercise group

Detailed Description

Peripheral nerve injury is common, affecting 3% of patients with limb trauma seen in the emergency department. Of those, young males who are active in the work force are most frequently inflicted. The functional loss does not only carry a huge personal burden but is also associated with substantial healthcare and socioeconomic costs. Indeed, based on data from the National Inpatient Sample in the US, estimated direct healthcare costs for patients who sustained upper limb nerve injury is over $1.2B per year. Although in previous studies the investigators found that conditioning electrical stimulation, a form of activity dependent therapy, enhances nerve regeneration following injury, it did not improve bone density. Therefore, alternative treatments capable of promoting bone formation, restoring muscle bulk and increasing nerve regeneration are needed.

Based on recent discoveries in animal studies, the goal of this randomized controlled clinical trial is to test the hypothesis that exercise training can accelerate nerve regeneration and significantly increase muscle bulk and bone density compared to surgery alone in patients with brachial plexus injury.

To test this hypothesis, patients with brachial plexus injury involving the musculocutaneous nerve will be randomized to the exercise or control group following nerve transfer surgery. This will be done using a redundant branch of the ulnar nerve to reinnervate the biceps muscle. To evaluate the treatment efficacy, compound muscle action potential of the biceps muscle will be used as the primary outcome measure to quantify reinnervation. The following anatomic and functional measures will be used as secondary outcome measures: i) muscle bulk of the biceps using MRI; ii) bone density of the humerus using dual-energy x-ray absorptiometry (DEXA) imaging; iii) quantitative force measurement for elbow flexion; iv) the Disability of Arm, Shoulder and Hand (DASH) instrument to assess disability, and v) the Canadian Occupational Performance Measure for limitations in participation.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Chan; Phone Number: 780-492-9343; Email: ming.chan@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C9
      • University of Alberta
      • Contact: Ming Chan; Phone Number: 780-492-9343; Email: ming.chan@ualberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adults age 18-60
• electrodiagnostically confirmed brachial plexus injury affecting the musculocutaneous nerve
• able to consent for participation.

Exclusion Criteria:

• individuals with additional neurological or musculoskeletal conditions that would affect elbow and hand function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise group; Each participant in the exercise group will undergo hand grip exercise for 30 minutes a day, 5 days a week for a total of 12 weeks. To activate the ulnar nerve innervated muscles, the exercise will be done using an electronic hand grip device with adjustable resistance individualized to the strength of each participant.	Other: Exercise group; Along with nerve transfer surgery, individuals in the exercise group will undergo handgrip exercise for 30 minutes a day, 5 days a week for a total of 12 weeks.
Experimental: Control group; Participants will carry out a stretch exercise routine that is not known to have any effect on nerve regeneration.	Other: Exercise group; Along with nerve transfer surgery, individuals in the exercise group will undergo handgrip exercise for 30 minutes a day, 5 days a week for a total of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor nerve conduction study	compound muscle action potential of the biceps muscle. Range: 0-7 mV. Higher scores signify better nerve regeneration	Baseline, 3, 6 and 9 months post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
magnetic resonance imaging (MRI)	muscle bulk of the biceps. Measure in cubic cm. Higher score signifies better nerve regeneration.	Baseline, 3, 6 and 9 months post surgery
dual energy x-rays absorptiometry (DEXA)	bone density - humerus (g/sq. m). Higher scores denote better outcome	Baseline, 3, 6 and 9 months post surgery
quantitative force measurement for elbow flexion using dynamometer DASH Questionnaire	to assess impairment (N). Higher scores denote better outcome	Baseline, 3, 6 and 9 months post surgery
Canadian Occupational Performance Measure (COPM)	to assess handicap and participation (Range 1-5). Higher scores denote better outcome	Baseline, 3, 6 and 9 months post surgery

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Royal Alexandra Hospital; Glenrose Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: April 5, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: Pro00128785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No