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

Universitaire Ziekenhuizen KU Leuven

Status: Enrolling

Conditions: CPSP; Central Post-stroke Pain

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05708729

CIV-22-09-040829 (Other Identifier)

S66772

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Device: MCS surgery for CPSP

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

Experimental group

Description:

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).

Treatment:

Device: MCS surgery for CPSP

Device: Vc-DBS surgery for CPSP