Spinal Cord Stimulation for Refractory Pain in Erythromelalgia

Erythromelalgia is a rare disorder characterized by red, warm, and painful extremities, which is often precipitated by warm conditions. The pathophysiology is incompletely understood. The management of pain in erythromelalgia is challenging as no single therapy has been found to be effective. Response to pharmacotherapy varies, meaning that the physician has to take a stepwise trial and error approach with each patient. Consequently, this disorder is often associated with poorer health-related quality of life. There is currently no consensus or guideline on management of pain in erythromelalgia. Spinal cord stimulation is a widely applied therapy to treat severe chronic pain of various origin. Case reports and anecdotal evidence suggest that this therapy might alleviate refractory pain in patients with erythromelalgia.

The aim of this trial is to evaluate the efficacy of spinal cord stimulation for refractory pain in erythromelalgia.

Study Overview

• Status: Recruiting
• Conditions: Erythromelalgia
• Intervention / Treatment: Procedure: Burst Spinal Cord Stimulation; Procedure: Sham spinal cord stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sasha Gulati, md prof; Phone Number: +47 73592020; Email: sasha.gulati@ntnu.no
• Study Contact Backup: Name: Sven M Carlsen, md prof; Phone Number: +47 91769528; Email: sven.carlsen@ntnu.no

Study Locations

• Norway
  • Halden, Norway
    • Recruiting
    • Halden Dermatology Center
    • Contact: Alexandros L Stefou, md
  • Strømmen, Norway
    • Recruiting
    • Aleris
    • Contact: Mari S Kvernebo, md
  • Tromsø, Norway
    • Recruiting
    • Universitetssykehuset Nord-Norge HF
    • Contact: Øystein Grimstad, md phd
  • Trondheim, Norway
    • Recruiting
    • St Olavs Hospital
    • Sub-Investigator: Sozaburo Hara, md
    • Sub-Investigator: Agnete M Gulati, md
    • Sub-Investigator: Jan Jørgensen, md

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. A diagnosis of primary or idiopathic erythromelalgia
2. Patients ≥18 years who have developed chronic pain that has remained refractory to medical treatment for ≥6 months.
3. Minimum pain intensity of 5/10 on a numeric rating scale NRS at baseline.
4. Successful two-week SCS testing period with tonic stimulation (≥2 points reduction in pain NRS from baseline). This means patients will experience paresthesia during the trial period of spinal cord stimulation.

Exclusion Criteria:

1. Coexisting conditions that would increase procedural risk (e.g., sepsis, coagulopathy).
2. History of laminectomy or posterior fusion at the thoracolumbar junction, where percutaneous electrode end tips are routinely placed.
3. Abnormal pain behavior and/or unresolved psychiatric illness.
4. Unresolved issues of secondary gain or inappropriate medication use.
5. Unfit for participation for any other reason as judged by the study physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Burst spinal cord stimulation (SCS); following implantation of a generator that sends pulses to a thin wire (lead), which delivers pulses to nerves along the spinal cord, the patients will initially undergo four six-week long periods with either burst SCS or no stimulation (sham) in a randomized order. During this period all patients will undergo two periods of SCS and sham stimulation.	Procedure: Burst Spinal Cord Stimulation; Burst stimulation utilizes complex programming to deliver high-frequency stimuli of a 40 Hz burst mode with 5 spikes at 500 Hz per spike delivered in a constant current mode; Procedure: Sham spinal cord stimulation; A pulse generator is implanted, but no spinal cord stimulation is provided
Sham Comparator: sham spinal cord stimulation (SCS); following implantation of a generator that sends pulses to a thin wire (lead), which delivers pulses to nerves along the spinal cord, the patients will initially undergo four six-week long periods with either burst SCS or no stimulation (sham) in a randomized order. During this period all patients will undergo two periods of SCS and sham stimulation.	Procedure: Burst Spinal Cord Stimulation; Burst stimulation utilizes complex programming to deliver high-frequency stimuli of a 40 Hz burst mode with 5 spikes at 500 Hz per spike delivered in a constant current mode; Procedure: Sham spinal cord stimulation; A pulse generator is implanted, but no spinal cord stimulation is provided

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in pain	assessed with a 0 -to-10 numerical rating scale (NRS)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in generic health-related quality of life	Assessed with the Euro-Qol-5D (5L)	6 months
Oswestry disability index (ODI) score	questionnaire originally designed to quantify disability for degenerative conditions of the lumbar spine, possibly a relevant outcome measure also in patients with erythromelalgia as it covers intensity of pain, ability to care for oneself, ability to walk, ability to sit, ability to lift, sexual function, ability to stand, social life, sleep quality, and ability to travel. The index is scored from 0 to 100. Zero means no disability and 100 reflects maximum disability.	6 months
Daily physical activity	measured by use of a body-worn accelerometer (activPALs from PAL Technologies Ltd., Glasgow, United Kingdom) attached by a waterproof tape to the midpoint of the patients' anterior right thigh	6 months
Severity of erythema	assessed using the Patient's Self-Assessment (PSA) scale	6 months
Health Care Provider's Costs	Cost-effectiveness (cost per gained quality-adjusted life year)	6 months

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Sasha Gulati, md prof, St. Olavs Hospital; Study Director: Geir Bråthen, md prof, St. Olavs Hospital

Publications and helpful links

General Publications

• O'Connell NE, Ferraro MC, Gibson W, Rice AS, Vase L, Coyle D, Eccleston C. Implanted spinal neuromodulation interventions for chronic pain in adults. Cochrane Database Syst Rev. 2021 Dec 2;12(12):CD013756. doi: 10.1002/14651858.CD013756.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Spinal Cord Stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Peripheral Vascular Diseases; Pain, Intractable; Erythromelalgia
• Other Study ID Numbers: 2019/159

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