Protocol Assessment of Motor Cortex rTMS for Treating Neuropathic Pain

NCT06964243 | Recruiting

• 1 other identifier: 2023-A01582-43
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathic pain is frequent and drugs relieves only 50% of the patients. Repetitive transcranial magnetic stimulation (rTMS) at high frequency (HF, usually 10Hz) applied on the primary motor cortex (M1) is an effective treatment of neuropathic pain. For the treatment of chronic pain, the 'classical' HF-rTMS protocol (CHF-rTMS) include one daily session for one or two weeks as an induction phase of treatment followed by a weekly session to produce analgesic effects. However, another type of protocol is based on a more spaced repetition of HF-rTMS sessions (SHF-rTMS), including intervals of several days or weeks between two sessions, but also resulting in a significant pain relief. However, CHF-rTMS and SHF-rTMS have never been compared regarding their analgesic efficacy. Alongside with pain, depression is the other clinical condition for which HF-rTMS is proposed as an effective therapeutic strategy. Another type of rTMS paradigm, called "accelerated intermittent theta burst stimulation" (ACC-iTBS) protocol has been recently proposed for the treatment of depression, combining a high number of pulses delivered per session and a high number of short-duration sessions grouped into a few days of stimulation. However, this type of protocol has never been applied for the treatment of chronic pain patients. Thus, for the first time we propose to compare in a pilot study the efficacy of three different rTMS protocols for the treatment of chronic neuropathic: CHF-rTMS, SHF-rTMS, and ACC-iTBS. In this study, two protocols two rTMS protocols (CHF-rTMS and ACC-iTBS) will share the same high total number of TMS pulses (i.e. 30 000 pulses) versus an rTMS protocol (SHF-rTMS) based on a lower total number of TMS pulses (i.e. 6 400 pulses), while one protocol (CHF-rTMS) will include a higher number of days of stimulation (i.e. 10 days) compared to the two other protocols (ACC-iTBS and SHF-rTMS) (i.e. 4 days). In all cases, the motor cortical target and the intensity of stimulation will the same. Thus, this study will be able to appraise the respective influence of the number of pulses delivered (the higher the number, the greater the effect) and the number of sessions (the higher the number, the more restrictive the implementation of treatment). That is to say that the new ACC-iTBS protocol could be an optimal compromise of a more efficacious and more easy-to-perform rTMS protocol for the treatment of patients with chronic pain.

Conditions

Chronic Pain Syndrome; Peripheral Neuropathic Pain

Keywords

rTMS; TMS-EEG; EEG; neuropathic pain; chronic pain; peripheral neuropathy; treatment; TBS; thetaburst stimulation; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Interference Scale of the short form of the Brief Pain Inventory (BPI)

  The 7-item Interference Scale of the short form of the Brief Pain Inventory measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. It uses a 0 to 10 numeric rating scales for each item rating. The minimum score is 0 (no interference of pain on daily living activities, ie better outcome) and the maximum score is 70 (maximal interference of pain on daily living activities, ie worse outcome).

  From enrollment to 5 weeks after the last TMS session

Secondary Outcomes (20)

• Average intensity of daily ongoing pain on a 0-10 numeric rating scale (NRS)

  From enrollment to 5 weeks after the last TMS session

• Average intensity of daily ongoing pain on a 0-5 verbal rating scale (VRS)

  From enrollment to 5 weeks after the last TMS session

• Patient global impression of change (PGIC)

  From enrollment to 5 weeks after the last TMS session

• Symptomatic profile of neuropathic pain on the Neuropathic Pain Symptom Inventory (NPSI)

  From enrollment to 1 weeks after the last TMS session

• Tendency to catastrophizing on the Pain Catastrophizing Scale (PCS)

  From enrollment to 1 weeks after the last TMS session

Study Arms (3)

Classical HF-rTMS (CHF-rTMS)

ACTIVE COMPARATOR

Stimulation was applied over the hand knob area of the primary motor cortex (M1), contralateral to the pain side, corresponding to the left hemisphere. The stimulation intensity was set at 80% of the resting motor threshold. Each session consisted of 30 trains of 100 pulses, delivered at a frequency of 10 Hz for 10 seconds per train, with an inter-train interval (ITI) of 20 seconds. This resulted in a total of 3,000 pulses per session, delivered over approximately 15 minutes. The treatment protocol included one session per day for 5 consecutive days during the first week. Subsequently, one session per week was performed during weeks 2, 3, 4, 5, and 7. In total, the protocol consisted of 10 sessions delivered over 7 weeks, with a cumulative number of 30,000 pulses.

Device: transcranial magnetic stimulation (TMS)

Spaced HF-rTMS (SHF-rTMS)

ACTIVE COMPARATOR

Stimulation was applied over the hand knob area of the primary motor cortex (M1), contralateral to the pain side, corresponding to the left hemisphere. The stimulation intensity was set at 80% of the resting motor threshold. Each session consisted of 20 trains of 80 pulses, delivered at a frequency of 20 Hz for 4 seconds per train, with an inter-train interval (ITI) of 80 seconds. This resulted in a total of 1,600 pulses per session, delivered over approximately 28 minutes. The treatment protocol included one session per week during weeks 1, 3, 5, and 7. In total, the protocol consisted of 4 sessions delivered over 4 weeks, with a cumulative number of 6,400 pulses.

Device: transcranial magnetic stimulation (TMS)

Accelerated iTBS (ACC-iTBS)

EXPERIMENTAL

Stimulation was applied over the hand knob area of the primary motor cortex (M1), contralateral to the pain side, corresponding to the left hemisphere. The stimulation intensity was set at 80% of the resting motor threshold. Each session consisted of 50 trains of 30 pulses, corresponding to 10 bursts (delivered at 5 Hz over 2 seconds), with each burst containing 3 pulses at 50 Hz (lasting 60 milliseconds). The inter-train interval (ITI) was 8 seconds. This resulted in a total of 1,500 pulses per session, delivered over approximately 8 minutes. The treatment protocol included 5 sessions per day, with an interval of 45 minutes between sessions, for 2 consecutive days during each stimulation week (from week 1 to week 7). In total, the protocol consisted of 20 sessions delivered over 4 days, with a cumulative number of 30,000 pulses.

Device: transcranial magnetic stimulation (TMS)

Interventions

transcranial magnetic stimulation (TMS) DEVICE

A brief, short, and repeated magnetic field is generated by 2 copper coils inducing an electric current that will propagate within the targeted cortical areas.

Also known as: TMS

Accelerated iTBS (ACC-iTBS); Classical HF-rTMS (CHF-rTMS); Spaced HF-rTMS (SHF-rTMS)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) existence of a definite peripheral neuropathy on both clinical and neurophysiological grounds, present for at least 6 months;
• (2) neuropathic pain clearly related to the neuropathy, as defined by a score ≥ 4/10 on the questionnaire "Douleur Neuropathique en 4 Questions" (DN4) ;
• (3) a score ≥ 4/10 on a 0-10 numerical rating scale (NRS) concerning the average intensity of daily ongoing pain;
• (4) age between 18 and 80 years;
• (5) affiliation with the social security system;
• (6) ability to provide signed informed consent.

You may not qualify if:

• (1) concomitant neurological (neurodegenerative disorders, migraine, epilepsy, stroke, tumor) or psychiatric illness;
• (2) contraindications related to TMS (intracranial ferromagnetic material);
• (3) drug-resistant or active epilepsy.

Sponsors & Collaborators

• Institut pour la Pratique et l'Innovation en PSYchologie appliquée (Institut Pi-Psy): lead

Study Sites (1)

Henri Mondor University Hospital

Créteil, Île-de-France Region, 94000, France

RECRUITING

MeSH Terms

Conditions

Neuralgia; Chronic Pain; Peripheral Nervous System Diseases

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Jean-Pascal Lefaucheur, MD, PhD

CONTACT

800-555-5555; Jean-pascal.lefaucheur@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of PiPsy Institute

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: May 9, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 19, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)