Posterior-superior Insula Deep Brain Stimulation in Refractory Peripheral Neuropathic Pain Patients — PSI-DBS  

Neuropathic Pain Clinical Trial

Official title: Posterior-superior Insula Deep Brain Stimulation in Refractory Peripheral Neuropathic Pain Patients

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Neuropathy;Peripheral
• Peripheral Nervous System Diseases

• NCT number: NCT04279548
• Study type: Interventional
• Source: University of Sao Paulo
• Status: Completed
• Phase: N/A
• Start date: January 1, 2018
• Completion date: July 1, 2021