Spinal Cord Stimulation for the Treatment of Therapy-Resistant Neuropathic Pain After Lumbar Spinal Surgery - A Randomized, Double-Blind, Sham-Controlled, Cross-over Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 50
- Locations
- 8
- Primary Endpoint
- Comparison between active subthreshold spinal cord stimulation and sham stimulation in reducing neuropathic leg pain
Study Overview
Brief Summary
Objective: To evaluate if spinal cord stimulation (SCS) performs better than placebo (no stimulation) in the long term to reduce persistent neuropathic leg pain refractory to medication and other conservative treatments in patients who have undergone lumbar spinal surgery.
Study design: Multicenter, double blind, randomized, sham-controlled trial.
After a positive SCS test trial, participants (18-70 years) will be implanted with a non-rechargeable SCS system providing active, subthreshold stimulation and followed for 12 months in a blinded cross-over design. The primary outcome measure is the difference in change in leg pain intensity scores using the Numeric Rating Scale (NRS) between a 3-month period with optimized subthreshold stimulation, and a 3-month period with no stimulation, as compared to baseline. Quality of life, physical functioning, sleep quality, return to work, and reduction in medication use will also be investigated.
Background: Up to 20% of patients who have undergone lumbar spinal surgery experience persistent back/leg pain leading to long-term reduction in functionality and quality of life. SCS is an established and safe, minimally invasive treatment for these patients when no further surgery is indicated and conservative therapies have been found to be ineffective. Placebo-controlled studies, comparing active and sham stimulation, were lacking until recently as traditional SCS relied on the patient feeling the stimulation (paresthesia). Technological progress with development of paresthesia-free stimulation forms now allows for the execution of placebo-controlled studies. A recent trial showing no significant difference in long-term effectiveness between active SCS and sham suffers from significant methodological shortcomings. This necessitates further sham-controlled studies to determine the effectiveness of SCS.
Detailed Description
- INTRODUCTION AND RATIONALE
SCS is an established and safe, minimally invasive treatment for patients with therapy-resistant chronic neuropathic pain. The treatment is based on the development of the gate-control theory presented in the mid-1960s as a way to dampen pain impulses at the spinal cord level. SCS treatment involves the insertion of electrode(s) in the epidural space, delivering weak electrical stimulation to the dorsal columns of the spinal cord to block pain impulses traveling to the brain. In patients experiencing sufficient pain relief (usually pain reduction over 50%) during a test trial period, an implantable pulse generator (IPG) is placed under the skin and connected to the electrode(s). Patients with chronic neuropathic pain may experience pain relief with SCS when other more invasive, surgical, and conservative treatments have been attempted and appeared to be ineffective.
The most common condition treated with SCS is enduring neuropathic back and/or leg pain after lumbar spinal surgeries, such as lumbar discectomy. Up to 20% of patients who have undergone lumbar spinal surgery for degenerative conditions exhibit new or persistent low back/leg pain, leading to impaired functionality and reduced quality of life. This condition is entitled persistent spinal pain syndrome type 2 (PSPS2, formerly known as failed back surgery syndrome). Randomized controlled trials (RCTs) with SCS have shown long-term pain reduction of up to 70-80% in this patient group. In these studies, the effectiveness of SCS is based on either comparing different forms of stimulation or comparing SCS with reoperations and medication treatments. However, placebo/sham-controlled studies, comparing active stimulation with inactive stimulation, were lacking until recently since traditional SCS relied on the patient feeling the stimulation (paresthesia), making it impossible to conduct blinded studies where the patient does not know if the stimulation is on or off. This has constituted a major disadvantage in terms of the strength of the scientific evidence for the effect of SCS treatment, as it is known that the placebo effect is significant in surgical treatments.
New SCS treatments for pain in which the patient does no longer experience paresthesia have been developed in recent years, which allows the execution of sham-controlled studies. A recently published study showed no significant difference between SCS and sham stimulation in long-term pain relief and improving physical functioning in patients with PSPS2, raising doubts about the effectiveness and use of the treatment, which is costly due to high material costs. However, this single study has significant methodological shortcomings. This necessitates further sham-controlled studies to ascertain whether SCS is an adequate treatment for chronic pain. The aim of the current study is to compare the long-term effect of paresthesia-free SCS with a sham treatment (no stimulation) in reducing neuropathic pain in patients with PSPS2. It is hypothesized that SCS treatment will be superior compared to treatment with sham stimulation. 2. OBJECTIVES
Primary Objective: To compare active subthreshold SCS with sham stimulation in reducing neuropathic leg pain.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
Statistician
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •History consistent with PSPS2 of at least 6 months after the last spinal surgery. The patient experienced no effect of conservative treatments and has been assessed as not eligible for further spinal surgery.
- •Patients between 18-70 years of age.
- •Average perceived pain intensity in one or both legs of 5 or more and average perceived pain intensity in the back of less than 3 measured with the validated 11-box NRS (0 no pain, 10 worst imaginable pain)
- •The patient should have been informed verbally and in writing about the study and should have provided informed written consent to participate.
- •Adequate pain relief effect (50% or more) after a two week trial with active test stimulation.
Exclusion Criteria
- •Subject is unable to understand or operate the SCS device.
- •Subject currently has an active implantable device including pacemakers, spinal cord stimulator or intrathecal drug delivery system.
- •Ongoing coagulation disorder.
- •Ongoing abuse of alcohol, drugs, or prescription opioids.
- •Active debilitating psychiatric illness.
- •Active malignancy.
- •Condition with increased general infection sensitivity, such as known immunodeficiency.
- •Expected lifespan <1 year.
- •Ongoing local infection or other skin disease where the IPG is planned to be placed.
- •Pregnancy.
Outcomes
Primary Outcomes
Comparison between active subthreshold spinal cord stimulation and sham stimulation in reducing neuropathic leg pain
Time Frame: Baseline and 3+3 months
The difference in change in neuropathic leg pain intensity scores measured by the numeric rating scale (NRS) questionnaire using a 0-10 scale between a 3-month period with subthreshold stimulation and a 3-month period with sham stimulation, as compared to baseline. Zero means no pain and 10 means the worst pain imaginable with higher scores indicating worse outcome.
Secondary Outcomes
- Comparison between active subthreshold spinal cord stimulation and sham stimulation(Baseline and 12 months)
Investigators
Kliment Gatzinsky
MD, PhD, Associate Professor
Sahlgrenska University Hospital