The Effect of Pre-operative Electrical Stimulation on Peripheral Nerve Regeneration.

NCT03205124 | Completed Phase 2 DMC

• 1 other identifier: UAlberta Pre-Conditioning
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

Traumatic injury to the peripheral nerves is most common in the young population with high associated costs to the patient, as well as to society. These range from acute healthcare cost to loss of productivity and rehabilitation. Despite major efforts in improving surgical technique, functional outcome has not significantly improved in the past thirty years. Irreversible denervation, atrophy of target muscles, and deranged sensation secondary to slow or aberrant axonal outgrowth remains a significant challenge. Although pre-operative conditioning of the injured peripheral nerve with electrical stimulation has shown promise in animal studies, it has not been tested in humans. In animal studies, pre-operative conditioning with electrical stimulation (ES) of the injured peripheral nerves promoted peripheral nerve regeneration in both sensory and motor fibres. We propose to conduct a clinical trial comparing 3 different treatments of complete digital nerve laceration before and after surgical repair. Participants will be randomized to one of three treatment arms: i) pre and post operative electrical stimulation, ii) pre-operative electrical stimulation alone , or iii) control group that receives sham pre and post-operative electrical stimulation. We will evaluate the effect of pre-operative electrical stimulation on axonal regeneration, as well as determine whether there is an additive effect of pre and post-operative electrical stimulation on sensory nerve axonal regeneration.

Conditions

Peripheral Nerve Injuries; Sensory Deficit; Digital Nerve Lesion

Outcome Measures

Primary Outcomes (1)

• Sensory nerve conduction studies

  An electromyography technique used to analyze sensory nerve recovery of the digital nerve.

  Change from baseline to 6 months

Secondary Outcomes (6)

• Semmes-Weinstein Monofilaments

  Baseline, 1,2,3,4,5,6 months

• Two Point Discrimination Disk

  Baseline, 1,2,3,4,5,6 months

• CASE (Computer assisted Sensory Examination)

  Baseline, 1,2,3,4,5,6 months

• Cold temperature detection threshold

  Baseline, 1,2,3,4,5,6 months

• DASH questionnaire

  Baseline, 1,2,3,4,5,6 months

Study Arms (3)

Pre-operative stimulation

EXPERIMENTAL

Patients randomized to this group will receive 1 hour of continuous electrical stimulation three days prior to scheduled surgical date. The frequency will be fixed at 20Hz and the voltage and duration of electrical pulses will be sequentially increased to the maximum tolerable limit. As the nerve becomes accustomed to the sensation of the stimulation, the voltage is increased to the next tolerable threshold and this is repeated throughout the one-hour period. Once the stimulation is complete, the stimulator is detached and the patient is informed of the surgical date. The wires are taken out at the conclusion of the pre-operative appointment. These patients will have fine gauge wires for post-operative sham stimulation implanted at the time of surgery. In the post-operative recovery room the stimulator is attached to their wires. However, the voltage will only be increased to a level they are able to sense.

Procedure: Electrical Stimulation

Sham stimulation

SHAM COMPARATOR

These patients will have the stimulator attached to their wires 3 days prior to scheduled surgical date and postoperatively as were in the previous groups. However, the voltage will only be increased to a level they are able to sense. The stimulator was then be turned off without the patients' knowledge. All connections are left in place for anhour duration. These patients will similarly have their wires removed after the conclusion of their pre-operative appointment and at the first post-operative follow-up within 1 week of surgery.

Procedure: Sham Stimulation

Pre and Post-operative stimulation

EXPERIMENTAL

Patients randomized to this group will receive 1 hour of continuous electrical stimulation three days prior to scheduled surgical date and then again immediately post operatively. The frequency will be fixed at 20Hz and the voltage and duration of electrical pulses will be sequentially increased to the maximum tolerable limit. As the nerve becomes accustomed to the sensation of the stimulation, the voltage is increased to the next tolerable threshold and this is repeated throughout the one-hour period. Patients randomized to this group will also receive 1 hour of continuous electrical stimulation post-operatively. These patients will have fine gauge wires for post-operative stimulation implanted at the time of surgery. In the post-operative recovery room the stimulator is attached to their wires. The frequency will be fixed at 20Hz and the voltage and duration of electrical pulses will be sequentially increased to the maximum tolerable limit for one hour.

Procedure: Electrical Stimulation

Interventions

Electrical Stimulation PROCEDURE

The experimental treatment involves implantation of 2 sterilized fine-gauge Teflon coated wires percutaneously. The ends of the wire are stripped for conductivity. Electrical stimulation is given at a fixed continuous frequency of 20Hz. The stimulus intensity is the maximum tolerable limit. The wires are then taped to the skin with surgical wound tape at a location away from the wound for strain relief. To ensure sterility, care is taken to dress the sutured wound and hand, as well apply the splint. The wires are removed either immediately at the conclusion of the pre-operative appointment and immediately after surgery or at the first surgical follow-up with dressing change, within one week of surgery.

Pre and Post-operative stimulation; Pre-operative stimulation

Sham Stimulation PROCEDURE

The experimental treatment involves implantation of 2 sterilized fine-gauge Teflon coated wires percutaneously. The ends of the wire are stripped for conductivity. Electrical stimulation is begun until the patient senses the stimulation, then the stimulation is discontinued.The wires are then taped to the skin with surgical wound tape at a location away from the wound for strain relief. To ensure sterility, care is taken to dress the sutured wound and hand, as well apply the splint. The wires are removed either immediately at the conclusion of the pre-operative appointment and immediately after surgery or at the first surgical follow-up with dressing change, within one week of surgery.

Sham stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18-65
• with a traumatic complete transection of one or more digital nerve(s) in the hand
• and receive surgery within 2 weeks of injury.

You may not qualify if:

• Age \<18y and \>65y,
• Uncontrolled diabetes (HbA1C\>8%),
• Cognitively impaired,
• Non-English speaking,
• Medically unfit for general anesthetic or personally refuse GA,
• Incomplete partial nerve lacerations,
• Crush injury,
• Concomitant bone injury in the same digit of nerve injury,
• Large nerve gap requiring graft, conduit or extreme joint flexion,
• Injury\>14days prior to surgical repair,
• Patients unable to comply with 6 month follow-up.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (2)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T5R2E1, Canada

Location

Related Publications (15)

• Salegio EA, Pollard AN, Smith M, Zhou XF. Macrophage presence is essential for the regeneration of ascending afferent fibres following a conditioning sciatic nerve lesion in adult rats. BMC Neurosci. 2011 Jan 20;12:11. doi: 10.1186/1471-2202-12-11.

  PMID: 21251261 BACKGROUND

• Al-Majed AA, Brushart TM, Gordon T. Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons. Eur J Neurosci. 2000 Dec;12(12):4381-90.

  PMID: 11122348 BACKGROUND

• Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci. 2000 Apr 1;20(7):2602-8. doi: 10.1523/JNEUROSCI.20-07-02602.2000.

  PMID: 10729340 BACKGROUND

• Brushart TM, Jari R, Verge V, Rohde C, Gordon T. Electrical stimulation restores the specificity of sensory axon regeneration. Exp Neurol. 2005 Jul;194(1):221-9. doi: 10.1016/j.expneurol.2005.02.007.

  PMID: 15899259 BACKGROUND

• Chan KM, Curran MW, Gordon T. The use of brief post-surgical low frequency electrical stimulation to enhance nerve regeneration in clinical practice. J Physiol. 2016 Jul 1;594(13):3553-9. doi: 10.1113/JP270892. Epub 2016 Mar 24.

  PMID: 26864594 BACKGROUND

• Elzinga K, Tyreman N, Ladak A, Savaryn B, Olson J, Gordon T. Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats. Exp Neurol. 2015 Jul;269:142-53. doi: 10.1016/j.expneurol.2015.03.022. Epub 2015 Apr 2.

  PMID: 25842267 BACKGROUND

• Geremia NM, Gordon T, Brushart TM, Al-Majed AA, Verge VM. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp Neurol. 2007 Jun;205(2):347-59. doi: 10.1016/j.expneurol.2007.01.040. Epub 2007 Feb 21.

  PMID: 17428474 BACKGROUND

• Gordon T, Amirjani N, Edwards DC, Chan KM. Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients. Exp Neurol. 2010 May;223(1):192-202. doi: 10.1016/j.expneurol.2009.09.020. Epub 2009 Oct 1.

  PMID: 19800329 BACKGROUND

• Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. J Hand Surg Am. 2000 May;25(3):391-414. doi: 10.1053/jhsu.2000.4165.

  PMID: 10811744 BACKGROUND

• Nix WA, Hopf HC. Electrical stimulation of regenerating nerve and its effect on motor recovery. Brain Res. 1983 Aug 1;272(1):21-5. doi: 10.1016/0006-8993(83)90360-8.

  PMID: 6616196 BACKGROUND

• Pockett S, Gavin RM. Acceleration of peripheral nerve regeneration after crush injury in rat. Neurosci Lett. 1985 Aug 30;59(2):221-4. doi: 10.1016/0304-3940(85)90203-4.

  PMID: 3877256 BACKGROUND

• Udina E, Furey M, Busch S, Silver J, Gordon T, Fouad K. Electrical stimulation of intact peripheral sensory axons in rats promotes outgrowth of their central projections. Exp Neurol. 2008 Mar;210(1):238-47. doi: 10.1016/j.expneurol.2007.11.007. Epub 2007 Nov 22.

  PMID: 18164293 BACKGROUND

• Wong JN, Olson JL, Morhart MJ, Chan KM. Electrical stimulation enhances sensory recovery: a randomized controlled trial. Ann Neurol. 2015 Jun;77(6):996-1006. doi: 10.1002/ana.24397. Epub 2015 May 4.

  PMID: 25727139 BACKGROUND

• Blesch A, Lu P, Tsukada S, Alto LT, Roet K, Coppola G, Geschwind D, Tuszynski MH. Conditioning lesions before or after spinal cord injury recruit broad genetic mechanisms that sustain axonal regeneration: superiority to camp-mediated effects. Exp Neurol. 2012 May;235(1):162-73. doi: 10.1016/j.expneurol.2011.12.037. Epub 2011 Dec 29.

  PMID: 22227059 BACKGROUND

• Moalem-Taylor G, Li M, Allbutt HN, Wu A, Tracey DJ. A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury. Mol Pain. 2011 Jan 5;7:1. doi: 10.1186/1744-8069-7-1.

  PMID: 21205324 BACKGROUND

MeSH Terms

Conditions

Peripheral Nerve Injuries

Interventions

Electric Stimulation

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Physical Stimulation; Investigative Techniques

Study Officials

• K Ming Chan, MB ChB

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Julie Beveridge, MD

  University of Alberta

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three arm randomized controlled study

Study Record Dates

• First Submitted: June 25, 2017
• First Posted: July 2, 2017
• Study Start: October 1, 2017
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)