Analgesic Effects of rTMS in Peripheral Neuropathic Pain

Not Applicable

Completed

• Conditions: Neuropathic Pain
• Interventions: Device: rTMS of prefrontal or motor cortex

• Registration Number: NCT02010281
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

This study aims to evaluate the long term efficacy over 25 weeks of repeated sessions of magnetic transcranial stimulation of the motor cortex or prefrontal cortex on average pain intensity, quality of life, sleep, neuropathic symptoms, return to work, in patients with peripheral neuropathic pain.

The medical device of study: transcranial magnetic stimulator (TMS).

Detailed Description

The present multicenter parallel session randomized placebo controlled study (4 French centers) aims to evaluate the long term efficacy over 25 weeks of repeated sessions of magnetic transcranial stimulation of the motor cortex or prefrontal cortex on average pain intensity (primary outcome) and several secondary outcome measures (e.g. quality of life, sleep, neuropathic symptoms, return to work), in patients with peripheral neuropathic pain.

The patients will be randomized to receive one of 3 treatment arms : rTMS of the motor cortex, rTMS of the prefrontal cortex, or placebo (sham stimulation) of the motor or prefrontal cortex. The study will be double blind, eg the patient and the investigator will not know the nature of treatment. the stimulation protocol will consist of an induction phasse of 5 daily sessions then a maintenance phase of several sessions : 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions 3 weeks apart. The statistical analysis will be conducted in the intent to treat population and using a modified ITT analysis excluding all the patients with protocol violation (primary outcome). The per protocol population will also be assessed.

Study Timeline

• Study First Submitted: 2013-11-07
• Study First Submitted QC: 2013-12-09
• Study First Posted: 2013-12-12
• Study Start: 2014-03
• Primary Completion: 2018-08-11
• Study Completion: 2019-05-11
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-18
• Last Update Posted: 2019-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

Inclusion Criteria

1. Peripheral neuropathic pain (unilateral or bilateral) probable or defined according to the criteria proposed in 2008 (Treede et al 2008),
2. Diagnostic DN4 questionnaire score greater than or equal to 4/10 (Bouhassira et al 2005),
3. chronic pain, the average intensity is greater than or equal to 40/100
4. Daily or almost daily pain (at least 4 days out of 7)
5. This pain is present for more than 6 months
6. Patients over 18 and under 75 years old
7. Patients who signed informed consent,
8. Patients whose pain medication is stable for 15 days before inclusion, and will not need to be changed during the study period,
9. Patients who can be monitored during the study period (30 weeks)
10. Patients insured by a health insurance plan or entitled.

Exclusion Criteria

1. Previous treatment using rTMS,
2. Work Accident or dispute
3. rTMS Cons-indications (ECT treatment during the previous month, epilepsy and / or a history of epilepsy; history of head trauma, neurosurgical lesion, intracranial hypertension, metal clip, pacemaker, pregnant or lactating women)
4. Abuse of drugs or psychoactive substances (DSM IV)
5. Central neuropathic pain,
6. Neuropathic pain within the framework of a progressive disease (HIV, cancer, non-stabilized system disease)
7. Neuropathic pain very limited extent, of neuroma type
8. Current major depression or psychosis according to DSM IV criteria,
9. Intermittent pain,
10. Pain for less than six months,
11. Presence of another pain more severe than the one justifying the inclusion
12. Lack of proper filling of self-assessment of pain from baseline and randomization (at least 4 weekly pain scores 7 days) notebooks
13. Lack of stability of pain scores on two successive evaluations, defined as a change of more than 30% between the two assessments of the average pain on the short questionnaire about pain between the first two visits inclusion
14. Subject unable to understand informed consent, under guardianship,
15. Subject who refuses to stop or can not stop prohibited treatment during the study,
16. Patients participating in another research protocol involving a drug within 30 days before enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rTMS of the motor cortex (Magventure)	rTMS of prefrontal or motor cortex	experimental : rTMS of the motor cortex : repetitive magnetic stimulation targeting the motor cortex assisted by neuronavigation
rTMS placebo (magventure)	rTMS of prefrontal or motor cortex	sham stimulation of the motor or prefrontal cortex with the placebo face of the device
rTMS prefrontal cortex (magventure)	rTMS of prefrontal or motor cortex	Experimental : repetitive transcranial stimulation targeting the prefrontal cortex as indicated by neuronavigation

Primary Outcome Measures

Name	Time	Method
Change in average pain intensity from baseline to week 25	each visit for up to 25 weeks	Change in average pain intensity from baseline to week 25, average pain intensity corresponds to average pain over the last 24 hours on the Brief Pain Inventory

Secondary Outcome Measures

Name	Time	Method
change in minimal pain intensity over the last 24 hours from baseline to week 25	each visit for up 25 weeks	change in minimal pain over the last 24 hours on the Brief Pain inventory
Proportion of responders to rTMS	at the end of treatment (25 weeks)	Proportion of responders (patients whose pain is improved by at least 30% and 50% compared to their pain before treatment
Sleep	each visit up to 25 weeks	sleep quality and quantity on MOS sleep
quality of life assessment	each visit up to 25 weeks	quality of life on the Eurogol questionnaire
Safety evaluation	each follow up visit for up to 25 weeks	Collection of side effects at each session and between sessions of rTMS
Pain right now	each visit up to 25 weeks	Pain right now immediately after each rtMS session and between sessions for up to 25 weeks
Predictors of the response	Baseline	Evaluation of predictors of response (nature of neuropathic symptoms, severity of anxiety or depressive symptoms, presence or absence of mechanical allodynia, or dramatization importance of catastrophism related to pain)
Return to work	25 weeks	Return to work on a specific questionnaire at the end of the study
Neuropathic symptoms	each visit up to 25 weeks	Neuropathic symptoms on the Neuropathic Pain Symptom Inventory
Onset of the analgesic effect of rTMS	one mont afer the beginning of rTMS	Determine the onset of the analgesic effect based on patient pain diaries for up to 1 month
Maximal pain	each visit up to 25 weeks	Maximal pain over the past 24 hours on the Brief Pain Inventory

Trial Locations

Locations (1)

Pain evaluation and treatement center, CHU Ambroise Paré; 🇫🇷 Boulogne Billancourt, Hauts-de-Seine, France