Treatment of Upper Limb Chronic Neuropathic Pain by Electrical Stimulation of the Brachial Plexus Nerve Roots (SIMPLEX)

Moderate to severe neuropathic pain has a prevalence of 5% in the French population, involving the upper limb (UL) in 47%. Invasive neuromodulation, mainly spinal cord stimulation (SCS) is recommended as a third line treatment in refractory chronic neuropathic pain when optimized medical treatments are not sufficient to control pain.

The implantation technique for BP roots PNS is based on the ultrasound-guided percutaneous inter-scalenic approach, routinely used for BP anesthetic blocks. As for SCS, BP PNS relies on chronic electrical stimulation of the nerve roots via chronically implanted devices (one lead connected to a subcutaneous generator).

However efficacy of BP PNS has never been evaluated in controlled conditions. Our objectives are to assess, in controlled conditions, the effects of BP PNS in term of pain relief, quality of life improvement and safety.

Study Overview

• Status: Recruiting
• Conditions: Neuralgia
• Intervention / Treatment: Device: electrical stimulation of the brachial plexus nerve roots; Other: sham stimulation

Detailed Description

Moderate to severe neuropathic pain has a prevalence of 5% in the French population, involving the upper limb (UL) in 47% . Invasive neuromodulation, mainly spinal cord stimulation (SCS) is recommended as a third line treatment in refractory chronic neuropathic pain when optimized medical treatments are not sufficient to control pain. However, SCS implanted at the cervical level, required to control UL pain, has shown its efficacy but has specific technical issues that limit its use: lead dislocation or breakage (0-43%), lead migration (0-12,5%), unwanted paresthesias in the trunk or the lower limb(s) (17%), paresthesias changes during head movements (48%). To avoid these limitations, peripheral nerve stimulation (PNS) targeting the UL nerve trunks or nerve roots of the brachial plexus (BP) has been proposed in short pioneering series reporting encouraging results .

The implantation technique for BP roots PNS is based on the ultrasound-guided percutaneous inter-scalenic approach, routinely used for BP anesthetic blocks. As for SCS, BP PNS relies on chronic electrical stimulation of the nerve roots via chronically implanted devices (one lead connected to a subcutaneous generator).

In a recent prospective series of 26 patients suffering from UL refractory pain, we reported that 20 patients still using the stimulation at last follow-up (28 months) experienced a mean pain relief of 67%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. Complications were rare: stimulation intolerance due to shock-like sensations, superficial infection, lead fractures and lead migration . However efficacy of BP PNS has never been evaluated in controlled conditions. Our objectives are to assess, in controlled conditions, the effects of BP PNS in term of pain relief, quality of life improvement and safety.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: DENYS FONTAINE; Phone Number: 0492034702; Email: fontaine.D@chu-nice.fr

Study Locations

• France
  • Lyon, France, 69500
    • Recruiting
    • CHU de Lyon
    • Contact: Patrick MERTENS
    • Contact: Manon Duraffourg
  • Nice, France, 06000
    • Recruiting
    • Chu de Nice
    • Contact: Denys FONTAINE
  • Poitiers, France, 86 0214
    • Recruiting
    • CHU De Poitiers
    • Contact: Philippe RIGOARD
    • Contact: Bénédicte BOUCHE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eligibility will be determined by trained clinicians with expertise in chronic pain and neuropathic pain.
• Patients between 18 and 80 years old
• suffering from moderate to severe (VAS score >5/10) chronic (duration> 12 months) neuropathic (DN4 score ≥ 4/10) unilateral pain - located in the upper limb.
• from peripheral origin, including complex regional pain syndrome type I and II, post-traumatic or post surgical pain.
• refractory to first and second line treatments for neuropathic pain according recent French recommendations and guidelines[6], including serotonin- noradrenaline reuptake inhibitor (SNRI) antidepressants (duloxetine and venlafaxine), gabapentin, pregabalin, tricyclic antidepressants, topical lidocaine, high-concentration capsaicin patches, psychotherapy and combinations of them.

Patient have signed informed consent

- Patient benefiting from French social insurance system

Exclusion Criteria:

• Brachial plexus avulsion
• Post-zoster neuropathic pain
• Phantom limb pain
• Patient unable to fill a self-administered questionnaire
• Patients with a chronic disease requiring repeated MRI monitoring
• Patients with contra-indication to general anesthesia, surgery or percutaneous BP approach.
• Patients with other pacemakers (cardiac pacemaker or defibrillator) or patients with a high risk to use a defibrillator due to a known cardiac disorder.
• Patients with instable neuropsychological or psychiatric disorders
• Vulnerable patients: pregnant or breast feeding, minor, adult under guardianship or deprived freedom

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BP PNS (experimental group); Patients with refractory upper limb neuropathic pain treated by chronic electrical stimulation of the brachial plexus nerve roots	Device: electrical stimulation of the brachial plexus nerve roots; treated by chronic electrical stimulation of the brachial plexus nerve roots
Active Comparator: sham stimulation (control group).; Patients with refractory upper limb neuropathic pain treated by sham stimulation	Other: sham stimulation; treated by sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacity	evaluation by the patient with quizz EQ5D (worse: 0-better: 20)	after 3 months of treatment
efficacity	evaluation by the patient with quizz VAS (worse: 0- better: 100)	after 3 months of treatment

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Denys FONTAINE, Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2024
• Primary Completion (Estimated): July 9, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 31, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 20-APN-01; 2021-A02538-33 (Other Identifier: ANSM)

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
• product manufactured in and exported from the U.S.: No