Posterior-superior Insula Deep Brain Stimulation in Refractory Peripheral Neuropathic Pain Patients
Condition: Neuropathic Pain; Neuropathy;Peripheral
MeSH terms: Neuralgia; Peripheral Nervous System Diseases
Study type: Interventional

Summary: 
      This study evaluates the long term pain relief after deep brain stimulation on
      posterior-superior insula (PSI) in patients with refractory peripheral neuropathic pain who
      responded to real but not to sham non-invasive stimulation by deep repetitive transcranial
      magnetic stimulation - PSI-drTMS.
    

Detailed description: 
      This study has two phases:

      Study I) This study is an extension of 690.455/NCT01932905, in which non invasive stimulation
      of the posterior-superior insula (PSI) was performed by deep repetitive transcranial magnetic
      stimulation (drTMS) in patients with central neuropathic pain. Patients responding to active
      stimulation would be invited to join a phase II study aiming at the long term effects of
      drTMS by deep brain stimulation (DBS) of the PSI. The original 690.455/NCT01932905 study was
      negative concerning pain intensity reduction compared to sham stimulation, its main outcome.
      However, in this same study, active but not sham PSI stimulation provided significant
      anti-nociceptive effects, with anti-allodynic and anti-hyperalgesic properties.

      This, and a number of experimental studies on peripheral neuropathic pain relief after PSI
      stimulation has lead us to perform an extension of the initial study, now including patients
      with refractory peripheral neuropathic pain to receive an induction series (5 consecutive
      daily stimulation sessions) of navigated PSI-deep rTMS against sham stimulation in a
      cross-over design. The calculate sample size for this cross-over screening study is 32. The
      primary endpoint is number of patients reaching significant pain relief (>50% pain intensity
      reduction assessed by visual analogue scale (VAS) ranging from 0: no pain, to 100mm:maximal
      pain imaginable) one week after the 5th stimulation session compared to baseline assessment.
      Other pain, quality of life and mood data were collected : pain interference with daily
      living (brief pain inventory), medication quantification score, neuropathic pain symptom
      inventory (NPSI).

      In this screening trial, actual responders: patients refractory peripheral neuropathic pain
      with >50% pain intensity reduction after real but not sham PSI-drTMS will be offered the
      opportunity to join a subsequent PSI-DBS phase II trial.

      Study II) In this phase, the PSI-DBS phase II trial (ethics review board number #690.455)
      will enroll 10 patients with refractory peripheral neuropathic pain from study 1 who
      responded to real but not to sham PSI-drTMS. Patients will have a stimulation electrode
      inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the
      insula contralateral to the pain side.

      After surgery, patients will be randomized to be in in either the ON or OFF DBS mode for
      three months, and then, after a flexible washout period, participants will be switched to the
      other corresponding mode (OFF or ON) for more three months. The study main outcome is number
      of responders (number of patients achieving >30% pain intensity reduction). Pain intensity
      will be measured on a 11-point visual numerical scale anchored at 0 (no pain) and 10 (maximal
      pain imaginable) and the score at the end of the three-month ON/OFF conditions will be
      compared to the respective baseline values in order too classify patients as responders or
      non-responders in each of the ON/OFF conditions. The main secondary outcome is safety, along
      with other clinical and general patients characteristics such as quality of life( QoL), mood,
      pain characteristics (McGill Pain Questionnaire-MPQ) and neuropathic pain symptom clusters
      (Neuropathic Pain Symptom Inventory).

      After the ON/OFF double blinded period (main outcome) patients will be maintained for 3
      months in the ON mode in a single blinded design, and then for more 6 months, maintained in
      the open phase of the study. This followup phase will allow us to gain insights into the
      potential long term effects of the treatment.
    

Intervention name(s): Deep Brain Stimulation
Intervention type(s): Device
Intervention description(s): Patients will have a stimulation electrode inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the insula contralateral to the pain side. After surgery will be randomized to be in in either the ON or OFF DBS
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Deep Brain Stimulation