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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
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.
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.
UZ Leuven
Leuven, Belgium
RECRUITINGThe 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.
Time frame: 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.
Time frame: After completion of the 4 weeks of active vs. inactive MCS or Vc-DBS (approximately at 9 months after surgery)
The relative difference in pain symptoms* immediately following 10 sessions of active vs. inactive rTMS;
\* as measured through the Neuropathic Pain Symptom Inventory (NPSI) and Patient Global Impression of Change (PGIC)
Time frame: 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;
\* as measured through the Medication Quantification Scale
Time frame: 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;
\* as measured through the Functional Independence Measure (FIM)
Time frame: 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;
\* as measured through the 36-Item Short-Form Health Survey (SF-36 QoLS)
Time frame: 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;
\* as measured through the Beck Depression Inventory (BDI)
Time frame: 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 pain symptoms* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
\* as measured through the Neuropathic Pain Symptom Inventory (NPSI) and Patient Global Impression of Change (PGIC)
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The relative difference in use of analgesics* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
\* as measured through the Medication Quantification Scale
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The relative difference in functionality* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
\* as measured through the Functional Independence Measure (FIM)
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The relative difference in quality of life* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
\* as measured through the 36-Item Short-Form Health Survey (SF-36 QoLS)
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The relative difference in mood* immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
\* as measured through the Beck Depression Inventory (BDI)
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The relative difference in metabolic activity (as measured through FDG-PET) in pain matrix areas immediately following 10 sessions of active vs. inactive rTMS;
Time frame: 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 metabolic activity (as measured through rsMRI) in pain matrix areas immediately following 10 sessions of active vs. inactive rTMS;
Time frame: 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 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;
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
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;
Time frame: immediately following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The spike rate in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
\*as measured through the microelectrodes (Vc-DBS) and paddle electrodes (MCS)
Time frame: Intraoperative
The spectral power* in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
\*as measured through the microelectrodes (Vc-DBS) and paddle electrodes (MCS)
Time frame: Intraoperative
Other neurophysiological parameters* in the presence or absence of noxious/innocuous sensory stimuli (selected through baseline QSM);
\*as measured through the microelectrodes (Vc-DBS) and paddle electrodes (MCS)
Time frame: Intraoperative
The spike rate* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
\*as measured postoperatively through the implanted electrodes
Time frame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The spectral power* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
\*as measured postoperatively through the implanted electrodes
Time frame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
Other neurophysiological parameters* in the presence and absence of noxious and innocuous sensory stimuli (selected through baseline QSM)
\*as measured postoperatively through the implanted electrodes
Time frame: following 4 weeks of active (with optimized stimulation parameters) vs. inactive MCS or Vc-DBS;
The safety for every procedure and during active and inactive rTMS, MCS and/or Vc-DBS.
\*as measured by the AEs and SAEs
Time frame: during procedure and during active and inactive rTMS, MCS and/or Vc-DBS.
The safety for every procedure
\*as measured by the AEs and SAEs
Time frame: during procedure
The safety during active and inactive rTMS
\*as measured by the AEs and SAEs
Time frame: during active and inactive rTMS
The safety during active and inactive MCS or Vc-DBS.
\*as measured by the AEs and SAEs
Time frame: during active and inactive MCS or Vc-DBS.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.