Clinical trial NCT05708729: Neuromodulation for Central Post-stroke Pain: Mechanism, Safety and Outcome
Official title: Neuromodulation for Central Post-stroke Pain: Mechanism, Safety and Outcome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Central Post-stroke Pain
CPSP
Keywords: neuromodulation
DBS
rTMS
MCS
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2023-02-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: In this project, we propose a prospective double-blind randomized crossover on/off study in 32 CPSP patients. These patients will undergo M1-rTMS and either MCS or Vc-DBS. Before and after active and inactive stimulation they will be assessed with clinical scales for pain, function, quality of life and depression. Adverse events will be monitored. This allows to measure the outcome and safety of neuromodulation in CPSP.

In addition, we will have functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) use. This will provide insight into the pathological changes in the pain circuitry, and the influence of neuromodulation.

Eligibility criteria: Inclusion Criteria:

1. Able to provide voluntary written informed consent of the participant prior to any screening procedures
2. Male or female patients
3. Aged 18-70 years
4. 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)

Exclusion Criteria:

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

Primary outcomes:
measure: The relative difference in pain intensity (Visual Analogue Scale; VAS) immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: After completion of all rTMS sessions (approximately one month before surgery)
measure: 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.
timeFrame: After completion of the 4 weeks of active vs. inactive MCS or Vc-DBS (approximately at 9 months after surgery)
Secondary outcomes:
measure: The relative difference in pain symptoms* immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in use of analgesics* immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in functionality* immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in quality of life* immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in mood* immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in pain symptoms* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in use of analgesics* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in functionality* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in quality of life* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in mood* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in metabolic activity (as measured through FDG-PET) in pain matrix areas immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in metabolic activity (as measured through rsMRI) in pain matrix areas immediately following 10 sessions of active vs. inactive rTMS;
timeFrame: 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
measure: The relative difference in metabolic activity (as measured through FDG-PET) in pain matrix areas immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The relative difference in metabolic activity (as measured through rsMRI) in pain matrix areas immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
timeFrame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The spike rate in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
timeFrame: Intraoperative
measure: The spectral power* in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
timeFrame: Intraoperative
measure: Other neurophysiological parameters* in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
timeFrame: Intraoperative
measure: The spike rate* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
timeFrame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The spectral power* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
timeFrame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: Other neurophysiological parameters* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
timeFrame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
measure: The safety for every procedure and during active and inactive rTMS, MCS and/or Vc-DBS.
timeFrame: during procedure and during active and inactive rTMS, MCS and/or Vc-DBS.
measure: The safety for every procedure
timeFrame: during procedure
measure: The safety during active and inactive rTMS
timeFrame: during active and inactive rTMS
measure: The safety during active and inactive MCS or Vc-DBS.
timeFrame: during active and inactive MCS or Vc-DBS.
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
References: