Neuromodulation for Central Post-stroke Pain: Mechanism, Safety and Outcome

NCT05708729 | Recruiting FDA Device

• 2 other identifiers: S66772CIV-22-09-040829
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Central post-stroke pain (CPSP) is an often pharmacorefractory type of neuropathic pain that develops in 8% of stroke patients. CPSP has been treated with three distinct types of neuromodulation (deep brain stimulation of the sensory thalamus (Vc-DBS), motor cortex repetitive transcranial magnetic stimulation (M1-rTMS), and motor cortex stimulation (MCS)), but the level of evidence for these procedures is very low. Moreover, data on the changes in pain brain circuitry in CPSP, and the effect of neuromodulation on this circuitry is very limited.

Conditions

Central Post-stroke Pain; CPSP

Keywords

neuromodulation; DBS; rTMS; MCS

Outcome Measures

Primary Outcomes (2)

• The relative difference in pain intensity (Visual Analogue Scale; VAS) immediately following 10 sessions of active vs. inactive rTMS;

  The patients will receive 10 sessions (1/d) of active and 10 sessions (1/d) of sham M1-rTMS with a 8-week wash-out period in between.

  After completion of all rTMS sessions (approximately one month before surgery)

• The relative difference in pain intensity (Visual Analogue Scale; VAS) immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS.

  Stimulation will be optimised for all patients up to 5 months post-surgery (Vc-DBS or MCS). After 2 weeks of wash-out, active and inactive stimulation will be offered in a double-blinded fashion for 4 weeks, with 2 weeks of wash-out in between.

  After completion of the 4 weeks of active vs. inactive MCS or Vc-DBS (approximately at 9 months after surgery)

Secondary Outcomes (24)

• The relative difference in pain symptoms* immediately following 10 sessions of active vs. inactive rTMS;

  Immediately after completion of the 10 sessions of active (1 per day, on 10 consecutive days) and 10 sessions of sham (1 per day, on 10 consecutive days) M1-rTMS with a 8 weeks washout period inbetween

• The relative difference in use of analgesics* immediately following 10 sessions of active vs. inactive rTMS;

  Immediately after completion of the 10 sessions of active (1 per day, on 10 consecutive days) and 10 sessions of sham (1 per day, on 10 consecutive days) M1-rTMS with a 8 weeks washout period inbetween

• The relative difference in functionality* immediately following 10 sessions of active vs. inactive rTMS;

  Immediately after completion of the 10 sessions of active (1 per day, on 10 consecutive days) and 10 sessions of sham (1 per day, on 10 consecutive days) M1-rTMS with a 8 weeks washout period inbetween

• The relative difference in quality of life* immediately following 10 sessions of active vs. inactive rTMS;

  Immediately after completion of the 10 sessions of active (1 per day, on 10 consecutive days) and 10 sessions of sham (1 per day, on 10 consecutive days) M1-rTMS with a 8 weeks washout period inbetween

• The relative difference in mood* immediately following 10 sessions of active vs. inactive rTMS;

  Immediately after completion of the 10 sessions of active (1 per day, on 10 consecutive days) and 10 sessions of sham (1 per day, on 10 consecutive days) M1-rTMS with a 8 weeks washout period inbetween

Study Arms (2)

Patients with CPSP which is pharmacorefractory and have a good analgesic response to M1-rTMS

EXPERIMENTAL

Diagnosed with definite CPSP (Treede-Klit criteria), which is pharmacorefractory (i.e. amitriptyline 75mg/d 4w, lamotrigine 200mg/d 8w and pregabalin 600mg/d resulting in \<50% VAS reduction and/or intolerable side-effects). A good analgesic response to M1-rTMS is defined as: ≥50% mean 10-d VAS reduction immediately following vs. before active M1-rTMS minus mean 10-d VAS reduction immediately following vs. pre sham M1-rTMS. A good analgesic response gives a high positive predictive value for pain reduction by MCS.

Device: MCS surgery for CPSP

Patients with CPSP which is pharmacorefractory with less analgesic M1-rTMS response

EXPERIMENTAL

Diagnosed with definite CPSP (Treede-Klit criteria), which is pharmacorefractory (i.e. amitriptyline 75mg/d 4w, lamotrigine 200mg/d 8w and pregabalin 600mg/d resulting in \<50% VAS reduction and/or intolerable side-effects). Patients with less analgesic M1-rTMS response (n≈20) will be 1:1 randomized to either MCS (≈10) or Vc-DBS (n≈10).

Device: MCS surgery for CPSP; Device: Vc-DBS surgery for CPSP

Interventions

MCS surgery for CPSP DEVICE

The investigational devices that will be used for the MCS surgeries are the following: the Vanta with AdaptiveStim Technology Primary cell neurostimulator or the Intellis Implantable Neurostimulator with AdaptiveStim Technology from Medtronic, Inc. (MN, USA). These implantable neurostimulators are intended to generate electrical pulses and to deliver stimulation trough one or more leads as part of a neurostimulation system for pain therapy in adults.

Patients with CPSP which is pharmacorefractory and have a good analgesic response to M1-rTMS; Patients with CPSP which is pharmacorefractory with less analgesic M1-rTMS response

Vc-DBS surgery for CPSP DEVICE

For the deep brain stimulation procedure, we will use Vercise stimulators from Boston Scientific together with the Cartesia Directional Leads or the Percept PC stimulator from Medtronic.

Patients with CPSP which is pharmacorefractory with less analgesic M1-rTMS response

Eligibility Criteria

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

You may qualify if:

• Able to provide voluntary written informed consent of the participant prior to any screening procedures
• Male or female patients
• Aged 18-70 years
• Diagnosed with definite CPSP (Treede-Klit criteria) (1, 9), which is pharmacorefractory (i.e. amitriptyline 75mg/d 4w, lamotrigine 200mg/d 8w and pregabalin 600mg/d resulting in \<50% VAS reduction and/or intolerable side-effects)

You may not qualify if:

• Aphasia
• Pregnancy or intention to become pregnant in the following year
• Medical inoperability
• Impossibility to temporarily withhold anticoagulation or anti-platelet medication
• Impossibility to undergo MRI, fMRI and/or PET imaging
• Complete destruction of the stimulation target region (M1 or Vc)
• Uncontrolled seizures
• Expected relocation in the following year.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Central Study Contacts

Philippe De Vloo, prof. dr.

CONTACT

016 344290; neurochirurgie@uzleuven.be

Daan Remans

CONTACT

016 344290; neurochirurgie@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinding for rTMS (active stimulation vs sham stimulation)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: February 1, 2023
• Study Start: January 24, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)