Clinical trial NCT02112474: The Pain Suppressive Effect of Alternative Spinal Cord Stimulation Frequencies
Official title: The Pain Suppressive Effect of Low Frequency Spinal Cord Stimulation Versus High Frequency Spinal Cord Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Failed Back Surgery Syndrome
Neuropathic Pain
Keywords: Failed Back Surgery Syndrome
Neuropathic pain
Leg Pain
Chronic Pain
Spinal Cord Stimulation
Neurostimulation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Diakonessenhuis, Utrecht
name: Rijnstate Hospital
name: Alrijne Hospital
name: Noordwest Ziekenhuisgroep
First posted: 2014-04-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Electrical stimulation of the spinal cord (Spinal Cord Stimulation or SCS) for pain relief has been used for decades. It is used most commonly in patients with chronic neuropathic leg pain, after spinal surgery. Conventional neurostimulation is applied in frequencies of 30 to 60 Hertz (Hz) and perceptible paraesthesias are felt. Stimulation using higher frequencies with sub perception paraesthesias has recently challenged the conventional form of neurostimulation.The high frequency stimulation appears to show better pain relief for both back and limb pain in comparison to low frequency SCS, and may also to be effective in some subjects who did not respond to low frequency SCS.

Detailed description: Rationale:

Electrical stimulation of the dorsal columns of the spinal cord (Spinal Cord Stimulation or SCS) for pain relief has been used in humans for several decades. The most common indication for SCS is the treatment of refractory neuropathic leg pain, particularly when these symptoms persist after an anatomically successful operation (Failed Back Surgery Syndrome or FBSS).

Low frequency - conventional - SCS (LF-SCS) is applied in frequencies ranging from 30 to 60 Hertz (Hz) and the subject feels paraesthesias in the painful area, which is considered the ideal situation. Recently, LF-SCS has been challenged by the development of stimulation modes at higher frequencies which provide pain relief at sub-perception threshold, i.e. without paraesthesias. A recent case series reported that High Frequency Spinal Cord Stimulation (HF-SCS) appears to show better pain relief for both back and limb pain in comparison to LF-SCS, and also to be effective in some subjects who did not respond to LF-SCS.

Objective:

The primary objective of this trial is to compare pain suppression in two groups of subjects with chronic unilateral limb pain as a result of FBSS .

Study design:

A prospective, double blind (subject, physician, statistician), multi-centre, randomized, crossover trial of SCS in the treatment of subjects with refractory neuropathic leg pain after back surgery.

Study population:

Patients with chronic neuropathic refractory unilateral leg pain

Intervention:

Patients will undergo neurostimulation with low and high frequency parameters, the order in which they receive treatment will be randomized

Main study endpoint:

Pain suppression in the short and long-term (24 days and 12 months)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Both methods of stimulation are standard clinical practice performed routinely in the study centres, both groups will receive this standard care. The only difference is change of stimulation frequency and the order in which it is applied.

Possible benefit to the subject is that both forms of stimulation will be evaluated. This may lead to a better quality of life in the HF-SCS Group as result of pain relief without paraesthesias. Furthermore, non-responders to LF-SCS may benefit from HF-SCS.

Eligibility criteria: Inclusion Criteria:

* Male/female, 18 years to 70 years
* Chronic, persistent, refractory, unilateral neuropathic limb pain, as a result of spinal surgery
* Failed conservative treatments for chronic pain including but not limited to pharmacological therapy, physical therapy and minimally interventional pain procedures for chronic pain
* Pain radiating in the leg, following segments L4 and/or L5 and/or S1 for at least 6 months
* Minimum baseline pain intensity as assessed by VAS of ≥ 50mm on 100mm scale in the primary pain area
* Subject is able and willing to provide informed consent
* Subject is able and willing to comply with the protocol and follow-up schedule
* Subject has been included for implantation according to standard criteria from the Dutch Neuromodulation Society

Exclusion Criteria:

* Back pain component of more than 20% or VAS \> 40mm on 100mm scale
* Bilateral limb pain
* Subjects with a previous SCS implantation.
* Changes in pain medication in the 2 months preceding the trial period;
* Expected inability of subjects to correctly operate the neurostimulation system
* Presence of any other clinically significant or disabling chronic pain condition -eg. hip arthrosis, rheumatoid arthritis, fibromyalgia, etc.
* History of coagulation disorders, lupus erythematosus, diabetes mellitus, or morbus Bechterew
* Symptoms or proof of any malignant disease
* Current use of medicines affecting coagulation which cannot be temporarily stopped
* Evidence of an active disruptive psychiatric disorder or other known condition significant enough to impact the perception of pain, compliance to intervention and/or ability to evaluate treatment outcome as determined by the investigator
* Life expectancy of less than 1 year
* Existing or planned pregnancy in the trial period
* BMI \>20 and \<35 - a minimum and maximum BMI limit are imposed due to the technical difficulties and risk of complications in underweight or morbidly obese subjects.

Primary outcomes:
measure: Visual Analog Pain Scores (VAS)
timeFrame: 24 days
Secondary outcomes:
measure: Visual Analog Pain scores (VAS)
timeFrame: 12 months
measure: EuroQoL 5Dimensions-3Levels
timeFrame: 1 month, 12 months
measure: Short Form-36
timeFrame: 1 month, 12 months
measure: Sleep questionnaire
timeFrame: 1 month, 12 months
measure: GPES
timeFrame: 1 month, 12 months
measure: Employment status
timeFrame: 12 months
measure: (Serious) Adverse Events
timeFrame: 12 months
Other outcomes:
Locations:
city: Velp
country: Netherlands
facility: Rijnstate Hospital
state: Gelderland
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
state: North Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: North Holland
city: Leiderdorp
country: Netherlands
facility: Alrijne Hospital
state: South Holland
city: Zeist
country: Netherlands
facility: Diakonessenhuis
state: Utrecht
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Markus W Hollmann, MD, PhD
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Frank Wille, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Jennifer S Breel, MPA,MSc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Breel J, Wille F, Wensing AGCL, Kallewaard JW, Pelleboer H, Zuidema X, Burger K, de Graaf S, Hollmann MW. A Comparison of 1000 Hz to 30 Hz Spinal Cord Stimulation Strategies in Patients with Unilateral Neuropathic Leg Pain Due to Failed Back Surgery Syndrome: A Multicenter, Randomized, Double-Blinded, Crossover Clinical Study (HALO). Pain Ther. 2021 Dec;10(2):1189-1202. doi: 10.1007/s40122-021-00268-7. Epub 2021 Jun 6.