Comparison of rTMS and H Coil in Neuropathic Pain
Condition: Central Pain Syndrome
MeSH terms: Neuralgia
Study type: Interventional

Summary: 
      rTMS of the motor cortex is an increasingly established analgesic technique for the treatment
      of neuropathic pain. However its efficacy is generally modest. One reason may be the that
      conventional rTMS targets only superficial and small cortical regions of the human brain. A
      newer cooled coil, the Hesed (H) coils, now allows deep and larger surface of stimulation and
      has been suggested to have analgesic effects in a small pilot trial in diabetic painful
      polyneuropathy. Based on its deeper mechanism of action and larger surface of stimulation, we
      hypothesize that this technique will be more effective than rTMS in patients with central
      pain, a highly unmet medical need. The primary objective of the present study will be to
      compare the efficacy of H coil, conventional rTMS and sham stimulation of the primary motor
      cortex in patients central neuropathic pain. Major secondary objectives will be to directly
      compare the analgesic efficacy of H coil versus conventional rTMS, and compare the efficacy
      of both techniques in patients with lower limb pain and those with upper limb pain/face. This
      will be a randomized tricentric sham controlled study
    

Detailed description: 
      This will be a tricenter randomized double blind sham controlled trial with stratified
      randomization based on the area of pain. Patients will first undergo MRI of the skull to
      determine the exact position of the coil of the motor cortex for neuronavigation with
      conventional rTMS. After providing informed consent, they will be randomly assigned to one of
      2 treatment groups: active rTMS and Hcoil or sham rTMS and sham Hcoil, according to a 2 : 1
      ratio (2 for active, 1 for placebo). For each treatment group (active or sham), the order of
      sessions will be again randomized according to a crossover design : thus each patient will
      receive successively either active rTMS followed by active H coil or active H coil followed
      by active rTMS or two sham stimulations (rTMS and H coil). Each treatment will be applied by
      an independent investigator not involved in the assessment or selection of patients. The
      treatment protocol will include 2 periods separated by an interval of 5 to 6 weeks depending
      on the potential residual analgesic effects to avoid carryover effects (patients whose pain
      intensity remains minimal after 6 weeks, eg less than 4 /10 on NRS, will not participate in
      the second crossover period of the study). Each session will consist of 5 consecutive
      stimulation visits of (active or sham) rTMS and H coil over 5 consecutive days. Each patient
      will thus receive a total of 10 stimulations (2 series of 5 active rTMS or H coil or 2 series
      of 5 sham rTMS or H coils) and will have a total of 15 visits, including one screening visit
      (V1), 10 stimulation visits (V2-V5 and V8-V13), and 4 poststimulation visits 1 and 3 weeks
      after each treatment period (V6, V7, V14, V15). Conventional magnetic stimulations will be
      applied with a MacPROX100 machine using neuronavigation system and sessions will consist of
      30 series of 10 second pulses with a frequency of 10 Hz and an interval of 20 seconds between
      each. The stimulation intensity used will be 80 % of the resting motor threshold.
      Conventional rTMS stimulations will target the primary motor cortex contralateral to the
      painful area or left side in case of bilateral pain and sham stimulation will be carried out
      with the opposite face of the coil (biface coil) of identical size, color and shape emitting
      a sound similar to that emitted by the active coil. H-coil rTMS will be delivered with the
      Brainsway H-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head
      corresponding to the primary motor cortex (H10 coil) and connected to a Masgtim Rapid2
      stimulatior (Mastim, Whitland, UK), while sham stimulation will be delivered with a sham coil
      placed in the helmet encasing the active rTMS coil. Active rTMS sessions with H-coil will use
      exactly the same parameters of stimulation as conventional rTMS, e.g. 30 consecutive trains
      of stimuli delivered at 10 Hz, at 80 % resting motor threshold (RMT), separated by intertrain
      intervals of 20 seconds.
    

Intervention name(s): rTMS
Intervention type(s): Device
Intervention description(s): Conventional magnetic stimulations will be applied with a MacPROX100 machine using neuronavigation system. H-coil rTMS will be delivered with the Brainsway H-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head corresponding to the primary motor cortex (H10 coil) and connected to a Masgtim Rapid2 stimulatior (Mastim, Whitland, UK), while sham stimulation will be delivered with a sham coil placed in the helmet encasing the active rTMS coil. Active rTMS sessions with H-coil will use exactly the same parameters of stimulation as conventional rTMS.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be randomly assigned to one of 2 treatment groups: active rTMS and Hcoil or sham rTMS and sham Hcoil, according to a 2 : 1 ratio (2 for active, 1 for placebo).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment