Placebo Effect In Spinal Cord Electrical Stimulation for Pain

NCT06585033 | Recruiting

• 1 other identifier: PISCES study
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 4

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.

Conditions

Chronic Postoperative Pain

Keywords

Spinal cord stimulation; Lumbar spine surgery; Chronic pain; Pain reduction; Placebo; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Comparison between active subthreshold spinal cord stimulation and sham stimulation in reducing neuropathic leg pain

  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.

  Baseline and 3+3 months

Secondary Outcomes (6)

• Comparison between active subthreshold spinal cord stimulation and sham stimulation

  Baseline and 3, 6 and 12 months

• Comparison between active subthreshold spinal cord stimulation and sham stimulation

  Baseline and 3, 6 and 12 months

• Comparison between active subthreshold spinal cord stimulation and sham stimulation

  Baseline and 3, 6 and 12 months

• Comparison between active subthreshold spinal cord stimulation and sham stimulation

  Baseline and 3, 6 and 12 months

• Comparison between active subthreshold spinal cord stimulation and sham stimulation

  Baseline and 3, 6 and 12 months

Study Arms (2)

No stimulation

SHAM COMPARATOR

Device: Spinal cord stimulation

Stimulation

ACTIVE COMPARATOR

Device: Spinal cord stimulation

Interventions

Spinal cord stimulation DEVICE

Stimulation off

No stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• Rijnstate Hospital: collaborator

Study Sites (4)

Department of Anaesthesiology and Pain Management, Rijnstate Hospital

Arnhem, 6800, Netherlands

RECRUITING

Department of Neurosurgery, Stavanger University hospital

Stavanger, 4019, Norway

RECRUITING

Department of Neurosurgery, Sahlgrenska University Hospital

Gothenburg, 41257, Sweden

RECRUITING

Department of Anesthesiology and Intensive Care/Pain Center, Sahlgrenska University Hospital Östra

Gothenburg, 41650, Sweden

RECRUITING

Related Publications (25)

• Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M, Levy RM, Abejon D, Buchser E, Burton A, Buvanendran A, Candido K, Caraway D, Cousins M, DeJongste M, Diwan S, Eldabe S, Gatzinsky K, Foreman RD, Hayek S, Kim P, Kinfe T, Kloth D, Kumar K, Rizvi S, Lad SP, Liem L, Linderoth B, Mackey S, McDowell G, McRoberts P, Poree L, Prager J, Raso L, Rauck R, Russo M, Simpson B, Slavin K, Staats P, Stanton-Hicks M, Verrills P, Wellington J, Williams K, North R; Neuromodulation Appropriateness Consensus Committee. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014 Aug;17(6):515-50; discussion 550. doi: 10.1111/ner.12208.

  PMID: 25112889 BACKGROUND

• Gatzinsky K. Spinal cord stimulation. In: Knotkova H, Rasche D, eds. Textbook of Neuromodulation: Principles, Methods and Clinical Applications. New York: Springer; 2015:35-52.

  BACKGROUND

• Zheng Y, Liu CW, Hui Chan DX, Kai Ong DW, Xin Ker JR, Ng WH, Wan KR. Neurostimulation for Chronic Pain: A Systematic Review of High-Quality Randomized Controlled Trials With Long-Term Follow-Up. Neuromodulation. 2023 Oct;26(7):1276-1294. doi: 10.1016/j.neurom.2023.05.003. Epub 2023 Jul 10.

  PMID: 37436342 BACKGROUND

• Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov 19;150(3699):971-9. doi: 10.1126/science.150.3699.971. No abstract available.

  PMID: 5320816 BACKGROUND

• Amirdelfan K, Webster L, Poree L, Sukul V, McRoberts P. Treatment Options for Failed Back Surgery Syndrome Patients With Refractory Chronic Pain: An Evidence Based Approach. Spine (Phila Pa 1976). 2017 Jul 15;42 Suppl 14:S41-S52. doi: 10.1097/BRS.0000000000002217.

  PMID: 28505029 BACKGROUND

• Rigoard P, Gatzinsky K, Deneuville JP, Duyvendak W, Naiditch N, Van Buyten JP, Eldabe S. Optimizing the Management and Outcomes of Failed Back Surgery Syndrome: A Consensus Statement on Definition and Outlines for Patient Assessment. Pain Res Manag. 2019 Feb 18;2019:3126464. doi: 10.1155/2019/3126464. eCollection 2019.

  PMID: 30911339 BACKGROUND

• Gatzinsky K, Eldabe S, Deneuville JP, Duyvendak W, Naiditch N, Van Buyten JP, Rigoard P. Optimizing the Management and Outcomes of Failed Back Surgery Syndrome: A Proposal of a Standardized Multidisciplinary Team Care Pathway. Pain Res Manag. 2019 Jul 8;2019:8184592. doi: 10.1155/2019/8184592. eCollection 2019.

  PMID: 31360272 BACKGROUND

• Parker SL, Mendenhall SK, Godil SS, Sivasubramanian P, Cahill K, Ziewacz J, McGirt MJ. Incidence of Low Back Pain After Lumbar Discectomy for Herniated Disc and Its Effect on Patient-reported Outcomes. Clin Orthop Relat Res. 2015 Jun;473(6):1988-99. doi: 10.1007/s11999-015-4193-1.

  PMID: 25694267 BACKGROUND

• Weir S, Samnaliev M, Kuo TC, Ni Choitir C, Tierney TS, Cumming D, Bruce J, Manca A, Taylor RS, Eldabe S. The incidence and healthcare costs of persistent postoperative pain following lumbar spine surgery in the UK: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). BMJ Open. 2017 Sep 11;7(9):e017585. doi: 10.1136/bmjopen-2017-017585.

  PMID: 28893756 BACKGROUND

• Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown LL, Yearwood TL, Bundschu R, Burton AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. 2015 Oct;123(4):851-60. doi: 10.1097/ALN.0000000000000774.

  PMID: 26218762 BACKGROUND

• Veizi E, Hayek SM, North J, Brent Chafin T, Yearwood TL, Raso L, Frey R, Cairns K, Berg A, Brendel J, Haider N, McCarty M, Vucetic H, Sherman A, Chen L, Mekel-Bobrov N. Spinal Cord Stimulation (SCS) with Anatomically Guided (3D) Neural Targeting Shows Superior Chronic Axial Low Back Pain Relief Compared to Traditional SCS-LUMINA Study. Pain Med. 2017 Aug 1;18(8):1534-1548. doi: 10.1093/pm/pnw286.

  PMID: 28108641 BACKGROUND

• Deer T, Slavin KV, Amirdelfan K, North RB, Burton AW, Yearwood TL, Tavel E, Staats P, Falowski S, Pope J, Justiz R, Fabi AY, Taghva A, Paicius R, Houden T, Wilson D. Success Using Neuromodulation With BURST (SUNBURST) Study: Results From a Prospective, Randomized Controlled Trial Using a Novel Burst Waveform. Neuromodulation. 2018 Jan;21(1):56-66. doi: 10.1111/ner.12698. Epub 2017 Sep 29.

  PMID: 28961366 BACKGROUND

• Mekhail N, Levy RM, Deer TR, Kapural L, Li S, Amirdelfan K, Hunter CW, Rosen SM, Costandi SJ, Falowski SM, Burgher AH, Pope JE, Gilmore CA, Qureshi FA, Staats PS, Scowcroft J, Carlson J, Kim CK, Yang MI, Stauss T, Poree L; Evoke Study Group. Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial. Lancet Neurol. 2020 Feb;19(2):123-134. doi: 10.1016/S1474-4422(19)30414-4. Epub 2019 Dec 20.

  PMID: 31870766 BACKGROUND

• North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98-106; discussion 106-7. doi: 10.1227/01.neu.0000144839.65524.e0.

  PMID: 15617591 BACKGROUND

• Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O'Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G, Richardson J, North RB. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007 Nov;132(1-2):179-88. doi: 10.1016/j.pain.2007.07.028. Epub 2007 Sep 12.

  PMID: 17845835 BACKGROUND

• Deer T, Gilligan C, Falowski S, Desai M, Pilitsis J, Jameson J, Moeschler S, Heros R, Tavel E, Christopher A, Patterson D, Wahezi S, Weisbein J, Antony A, Funk R, Ibrahim M, Lim C, Wilson D, Fishell M, Scarfo K, Dickerson D, Braun E, Buchanan P, Levy RM, Miller N, Duncan J, Xu J, Candido K, Kreiner S, Fahey ME, Yue J. Treatment of Refractory Low Back Pain Using Passive Recharge Burst in Patients Without Options for Corrective Surgery: Findings and Results From the DISTINCT Study, a Prospective Randomized Multicenter Controlled Trial. Neuromodulation. 2023 Oct;26(7):1387-1399. doi: 10.1016/j.neurom.2023.07.009. Epub 2023 Aug 28.

  PMID: 37642628 BACKGROUND

• Dettori JR, Norvell DC, Chapman JR. The Art of Surgery: The Strange World of the Placebo Response. Global Spine J. 2019 Sep;9(6):680-683. doi: 10.1177/2192568219861972. Epub 2019 Jul 17. No abstract available.

  PMID: 31448203 BACKGROUND

• Karjalainen T, Heikkinen J, Busija L, Jokihaara J, Lewin AM, Naylor JM, Harris L, Harris IA, Buchbinder R, Adie S. Use of Placebo and Nonoperative Control Groups in Surgical Trials: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Jul 1;5(7):e2223903. doi: 10.1001/jamanetworkopen.2022.23903.

  PMID: 35895060 BACKGROUND

• Duarte RV, Nevitt S, McNicol E, Taylor RS, Buchser E, North RB, Eldabe S. Systematic review and meta-analysis of placebo/sham controlled randomised trials of spinal cord stimulation for neuropathic pain. Pain. 2020 Jan;161(1):24-35. doi: 10.1097/j.pain.0000000000001689.

  PMID: 31453983 BACKGROUND

• Hara S, Andresen H, Solheim O, Carlsen SM, Sundstrom T, Lonne G, Lonne VV, Taraldsen K, Tronvik EA, Oie LR, Gulati AM, Sagberg LM, Jakola AS, Solberg TK, Nygaard OP, Salvesen OO, Gulati S. Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial. JAMA. 2022 Oct 18;328(15):1506-1514. doi: 10.1001/jama.2022.18231.

  PMID: 36255427 BACKGROUND

• Thomson S, Kallewaard JW, Gatzinsky K. Spinal Cord Burst Stimulation vs Placebo Stimulation for Patients With Chronic Radicular Pain After Lumbar Spine Surgery. JAMA. 2023 Mar 14;329(10):847. doi: 10.1001/jama.2022.24742. No abstract available.

  PMID: 36917057 BACKGROUND

• Taylor RS, Eldabe S. Placebo (Sham) Controlled Trials of Spinal Cord Stimulation. Neuromodulation. 2023 Feb;26(2):474-475. doi: 10.1016/j.neurom.2022.11.013. Epub 2022 Dec 15. No abstract available.

  PMID: 36526546 BACKGROUND

• Paz-Solis J, Thomson S, Jain R, Chen L, Huertas I, Doan Q. Exploration of High- and Low-Frequency Options for Subperception Spinal Cord Stimulation Using Neural Dosing Parameter Relationships: The HALO Study. Neuromodulation. 2022 Jan;25(1):94-102. doi: 10.1111/ner.13390.

  PMID: 35041592 BACKGROUND

• Thomson SJ, Tavakkolizadeh M, Love-Jones S, Patel NK, Gu JW, Bains A, Doan Q, Moffitt M. Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial. Neuromodulation. 2018 Jan;21(1):67-76. doi: 10.1111/ner.12746. Epub 2017 Dec 8.

  PMID: 29220121 BACKGROUND

• Metzger CS, Hammond MB, Paz-Solis JF, Newton WJ, Thomson SJ, Pei Y, Jain R, Moffitt M, Annecchino L, Doan Q. A novel fast-acting sub-perception spinal cord stimulation therapy enables rapid onset of analgesia in patients with chronic pain. Expert Rev Med Devices. 2021 Mar;18(3):299-306. doi: 10.1080/17434440.2021.1890580. Epub 2021 Mar 3.

  PMID: 33656411 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Chronic Pain

Interventions

Spinal Cord Stimulation

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation

Study Officials

• Kliment Gatzinsky, MD, PhD

  Department of Neurosurgery, Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kliment Gatzinsky, MD, PhD

CONTACT

+46733407733; kliment.gatzinsky@neuro.gu.se

Jan Willem Kallewaard, MD, PhD

CONTACT

+31622412029; jkallewaard@rijnstate.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Statistician
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Associate Professor

Study Record Dates

• First Submitted: September 2, 2024
• First Posted: September 5, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

SE (2); NO (1); NL (1)