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

NCT ID: NCT05708729

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-24
• Study Completion Date: 2026-04-30

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.

Conditions

Central Post-stroke Pain; CPSP

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

MCS surgery for CPSP

Intervention Type: 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 with less analgesic M1-rTMS response

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).

Group Type: EXPERIMENTAL

MCS surgery for CPSP

Intervention Type: 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.

Vc-DBS surgery for CPSP

Intervention Type: 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.

Interventions

MCS surgery for CPSP

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.

Intervention Type: DEVICE

Vc-DBS surgery for CPSP

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.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Philippe De Vloo, prof. dr.

Role: CONTACT

neurochirurgie@uzleuven.be

016 344290

Daan Remans

Role: CONTACT

neurochirurgie@uzleuven.be

016 344290

Facility Contacts

Philippe De Vloo, prof.dr.

Role: primary

neurochirurgie@uzleuven.be

016 344290

Other Identifiers

CIV-22-09-040829

Identifier Type: OTHER

Identifier Source: secondary_id

S66772

Identifier Type: -

Identifier Source: org_study_id