Clinical trial NCT02010281: Analgesic Effects of rTMS in Peripheral Neuropathic Pain
Official title: Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) of the Motor or Prefrontal Cortex in Peripheral Neuropathic Pain: a Multicenter Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neuropathic Pain
Keywords: rTMS
peripheral neuropathic pain
randomized controlled trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2013-12-12
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in average pain intensity from baseline to week 25
timeFrame: each visit for up to 25 weeks
Secondary outcomes:
measure: change in minimal pain intensity over the last 24 hours from baseline to week 25
timeFrame: each visit for up 25 weeks
measure: quality of life assessment
timeFrame: each visit up to 25 weeks
measure: Proportion of responders to rTMS
timeFrame: at the end of treatment (25 weeks)
measure: Predictors of the response
timeFrame: Baseline
measure: Safety evaluation
timeFrame: each follow up visit for up to 25 weeks
measure: Onset of the analgesic effect of rTMS
timeFrame: one mont afer the beginning of rTMS
measure: Return to work
timeFrame: 25 weeks
measure: Maximal pain
timeFrame: each visit up to 25 weeks
measure: Pain right now
timeFrame: each visit up to 25 weeks
measure: Sleep
timeFrame: each visit up to 25 weeks
measure: Neuropathic symptoms
timeFrame: each visit up to 25 weeks
Other outcomes:
Locations:
city: Boulogne Billancourt
country: France
facility: Pain evaluation and treatement center, CHU Ambroise Paré
state: Hauts-de-Seine
Study officials:
affiliation: Pain evaluation and treatment center, CHU A Paré, 92104 Boulogne Billancourt, France
name: NADINE ATTAL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Attal N, Poindessous-Jazat F, De Chauvigny E, Quesada C, Mhalla A, Ayache SS, Fermanian C, Nizard J, Peyron R, Lefaucheur JP, Bouhassira D. Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial. Brain. 2021 Dec 16;144(11):3328-3339. doi: 10.1093/brain/awab208.