Study of rTMS Analgesic Effect in Chronic Neuropathic Pain, (NEUROSTIM)

Randomized Double-blind Study of rTMS Analgesic Effect in Chronic Neuropathic Pain. Comparison Between Three Groups: Motor Cortex Stimulation by the Classic Coil B65, Deeper Stimulation by the Coil B70 and Placebo Stimulation. Analysis of Long-term rTMS-induced Brain Changes Using fMRI.

The purpose of this study is to compare the analgesic effectiveness of three modes of repetitive Transcranial Magnetic Stimulation (rTMS) in chronic neuropathic pain:

• Classical rTMS stimulation
• Deeper rTMS stimulation
• Sham rTMS stimulation

Study Overview

• Status: Recruiting
• Conditions: Chronic Neuropathic Pain
• Intervention / Treatment: Device: RepetitiveTranscranial Magnetic Stimulation (rTMS)

Detailed Description

Conduct of study:

• Entry into the study: After informed consent, patients will be randomised. The physician responsible for conducting neurostimulation sessions will make the randomization via an interactive web response system (IWRS). Only this physician will have the knowledge of the group allocated to the patient.
• Baseline : Patients, will record on a diary form, a daily Visual Numeric Scale(VNS) of Pain Intensity for 1 week.
• Treatment sessions: after the baseline, sessions of neurostimulation will begin for seven weeks.
• After the end of neurostimulation sessions, patients will be followed for 2 weeks.
• Throughout their participation in the study, patients will plot on a diary form their daily VNS.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hasan HODAJ, MD; Phone Number: 33 04-76-76-52-13; Email: HHodaj@chu-grenoble.fr

Study Locations

• France
  • Isère
    • Grenoble, Isère, France, 38043
      • Recruiting
      • Centre de la douleur, CHU Grenoble Alpes
      • Contact: HODAj Hasan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient's written consent
• Affiliated with social security system
• Male or female, suffering for more than a year from unilateral refractory neuropathic pain: hemi-body, upper limb, lower limb and facial chronic pain.
• Patient whose analgesic treatment, is stable for at least 1 month.
• Patient not responding to conventional treatments
• Prescreening EVN >3

Exclusion Criteria:

• History of drug addiction, epilepsy, cranial trauma
• History of psychiatric disorder
• Patients previously treated with rTMS
• Patient with intracranial ferromagnetic material or implanted stimulator
• New treatment for less than one month
• Pregnant or Breastfeeding woman
• Patient who does not understand the study protocol
• Persons who are protected under the act.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Classic rTMS Stimulation using the B65 Coil	Device: RepetitiveTranscranial Magnetic Stimulation (rTMS); The rTMS protocol consist of one session per day for five days during the first week, then three sessions the second week and then one session the third week, followed by two monthly sessions.
Experimental: Deeper rTMS Stimulation using the B70 Coil	Device: RepetitiveTranscranial Magnetic Stimulation (rTMS); The rTMS protocol consist of one session per day for five days during the first week, then three sessions the second week and then one session the third week, followed by two monthly sessions.
Sham Comparator: control group with a sham stimulation using a sham coil	Device: RepetitiveTranscranial Magnetic Stimulation (rTMS); The rTMS protocol consist of one session per day for five days during the first week, then three sessions the second week and then one session the third week, followed by two monthly sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of Pain.	Comparison between the 3 groups of the evolution of the weekly value of the Visual Numeric Scale (VNS): The patient will raise his pain level on a follow-up diary each day. The VNS average will be calculated for each week. The NSV is a 10-point scale, ranging from 0 (worse) to 10 (better).	Pain progression will be assessed from week 1 (before treatment) to week 7 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assesment of Potential Changes in Sensory-motor Cortical Maps Induced by rTMS	Comparison between the 3 groups of changes in sensory-motor cortical maps using Functional magnetic resonance imaging (FMRI).	Day 60 from the beginning of rTMS treatment compared to baseline.
Rate of Responding Patients.	Comparison between the 3 groups of the rate of responding patients. Responding patients is defined by a 30% reduction in pain intensity assessed with VNS.	week 7 compared with baseline
Assessment of Overall Patient Improvement.	Comparison between the 3 groups of the overall patient improvement using the Clinical Global Impression of Change scale (CGI).The CGI is a 7-point scale, ranging from 1 (better) to 7 (worse).	Day 30 and day 60 from the beginning of rTMS treatment compared to baseline
Quality of Life Improvement.	Comparison between the 3 groups of the improvement of quality of life using the SF12 (Short Form 12) questionnaire.SF12 includes a mental and social score ranging from 5.89 to 71.97 and a physical score ranging from 9.95 to 70. a high score indicates a better quality of life.	Day 30 and day 60 from the beginning of rTMS treatment compared to baseline
Evolution of Anxiety and Depressive Traits.	Comparison between the 3 groups of the improvement of anxiety and depressive traits using the HADS questionnaire (Hospital Anxiety and Depression Scale).the HADS score varies between 0 and 42. zero corresponding to the best score.	Day 30 and day 60 from the beginning of rTMS treatment compared to baseline
Evolution of Symptomatological Profiles of Neuropathic Pain.	Comparison between the 3 groups of symptomatological profiles of neuropathic pain using NPSI questionnaire (Neuropathic Pain Symptom Inventory).	Day 30 and day 60 from the beginning of rTMS treatment compared to baseline.
Sympathetic Autonomic System Injury and Small Fiber Neuropathy.	Comparison between the 3 groups of sympathetic autonomic system injury and small fiber neuropathy using the Sudoscan® device.	Day 60 from the beginning of rTMS treatment compared to baseline.
Autonomous System Assessement.	Comparison between the 3 groups of changes in skin tension and conductance during fMRI examination.	Day 60 from the beginning of rTMS treatment compared to baseline.
Evolution of the use of analgesic treatments.	Comparison between the 3 groups of the evolution of the use of analgesic treatments reported on the diary.	From baseline to day 60.
Analgesic Response Analysis	Comparison between the 3 groups of the evolution of the weekly EVN average according to the clinical profile of patients	From baseline to day 60.
Improvement of pain triggered by a stimulus (allodynia).	Comparison between the 3 groups of allodynia improvement.	Day 30 and day 60 from the beginning of rTMS treatment compared to baseline.

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Hasan HODAJ, MD, CHUGA

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Estimate): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: rTMS; Repetitive Transcranial Magnetic Stimulation; Chronic neuropathic pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 38RC20192

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No