Comparison of rTMS and H Coil in Neuropathic Pain (HNEP)

October 13, 2022 updated by: Nadine ATTAL, Hospital Ambroise Paré Paris

Comparison of the Analgesic Effects of Two Methods of Repetitive Magnetic Transcranial Stimulation: A Randomized Double Blind Sham Controlled Study in Patients With Central Neuropathic Pain

rTMS of the motor cortex is an increasingly established analgesic technique for the treatment of neuropathic pain. However its efficacy is generally modest. One reason may be the that conventional rTMS targets only superficial and small cortical regions of the human brain. A newer cooled coil, the Hesed (H) coils, now allows deep and larger surface of stimulation and has been suggested to have analgesic effects in a small pilot trial in diabetic painful polyneuropathy. Based on its deeper mechanism of action and larger surface of stimulation, we hypothesize that this technique will be more effective than rTMS in patients with central pain, a highly unmet medical need. The primary objective of the present study will be to compare the efficacy of H coil, conventional rTMS and sham stimulation of the primary motor cortex in patients central neuropathic pain. Major secondary objectives will be to directly compare the analgesic efficacy of H coil versus conventional rTMS, and compare the efficacy of both techniques in patients with lower limb pain and those with upper limb pain/face. This will be a randomized tricentric sham controlled study

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This will be a tricenter randomized double blind sham controlled trial with stratified randomization based on the area of pain. Patients will first undergo MRI of the skull to determine the exact position of the coil of the motor cortex for neuronavigation with conventional rTMS. After providing informed consent, they will be randomly assigned to one of 2 treatment groups: active rTMS and Hcoil or sham rTMS and sham Hcoil, according to a 2 : 1 ratio (2 for active, 1 for placebo). For each treatment group (active or sham), the order of sessions will be again randomized according to a crossover design : thus each patient will receive successively either active rTMS followed by active H coil or active H coil followed by active rTMS or two sham stimulations (rTMS and H coil). Each treatment will be applied by an independent investigator not involved in the assessment or selection of patients. The treatment protocol will include 2 periods separated by an interval of 5 to 6 weeks depending on the potential residual analgesic effects to avoid carryover effects (patients whose pain intensity remains minimal after 6 weeks, eg less than 4 /10 on NRS, will not participate in the second crossover period of the study). Each session will consist of 5 consecutive stimulation visits of (active or sham) rTMS and H coil over 5 consecutive days. Each patient will thus receive a total of 10 stimulations (2 series of 5 active rTMS or H coil or 2 series of 5 sham rTMS or H coils) and will have a total of 15 visits, including one screening visit (V1), 10 stimulation visits (V2-V5 and V8-V13), and 4 poststimulation visits 1 and 3 weeks after each treatment period (V6, V7, V14, V15). Conventional magnetic stimulations will be applied with a MacPROX100 machine using neuronavigation system and sessions will consist of 30 series of 10 second pulses with a frequency of 10 Hz and an interval of 20 seconds between each. The stimulation intensity used will be 80 % of the resting motor threshold. Conventional rTMS stimulations will target the primary motor cortex contralateral to the painful area or left side in case of bilateral pain and sham stimulation will be carried out with the opposite face of the coil (biface coil) of identical size, color and shape emitting a sound similar to that emitted by the active coil. H-coil rTMS will be delivered with the Brainsway H-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head corresponding to the primary motor cortex (H10 coil) and connected to a Masgtim Rapid2 stimulatior (Mastim, Whitland, UK), while sham stimulation will be delivered with a sham coil placed in the helmet encasing the active rTMS coil. Active rTMS sessions with H-coil will use exactly the same parameters of stimulation as conventional rTMS, e.g. 30 consecutive trains of stimuli delivered at 10 Hz, at 80 % resting motor threshold (RMT), separated by intertrain intervals of 20 seconds.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Oslo, Norway, 0424
        • Department of Pain Management and Research, Oslo University Hospital and Faculty of Medicine, University of Oslo, Norway

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age over 18 years and less than 80 years
  • Average pain intensity ≥ 4/10 at screening and randomization
  • Persistent pain for at least 6 months
  • Stable pharmacological treatment for pain
  • Central neuropathic pain as diagnosed by DN4 and NeuPSIG classification algorithm related to stable multiple sclerosis, spinal cord lesion or past stroke

Exclusion Criteria:

  • Any clinically significant or unstable medical or psychiatric disorder
  • History of substance abuse
  • Litigation
  • Pregnancy/lactation
  • Contraindication to rTMS or Hcoil
  • Intermittent pain, more severe pain than neuropathic pain and diffuse pain

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Active rTMS and H coil
Device: rTMS
Conventional magnetic stimulations will be applied with a MacPROX100 machine using neuronavigation system. H-coil rTMS will be delivered with the Brainsway H-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head corresponding to the primary motor cortex (H10 coil) and connected to a Masgtim Rapid2 stimulatior (Mastim, Whitland, UK), while sham stimulation will be delivered with a sham coil placed in the helmet encasing the active rTMS coil. Active rTMS sessions with H-coil will use exactly the same parameters of stimulation as conventional rTMS.
Placebo Comparator: sham rTMS and Hcoil
Device: rTMS
Conventional magnetic stimulations will be applied with a MacPROX100 machine using neuronavigation system. H-coil rTMS will be delivered with the Brainsway H-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head corresponding to the primary motor cortex (H10 coil) and connected to a Masgtim Rapid2 stimulatior (Mastim, Whitland, UK), while sham stimulation will be delivered with a sham coil placed in the helmet encasing the active rTMS coil. Active rTMS sessions with H-coil will use exactly the same parameters of stimulation as conventional rTMS.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the self reported average pain intensity (NRS from 0 to 10) over the past 24 hours from baseline to week 3 after the end of the last stimulation
Time Frame: the average of pain scores (NRS for pain intensity) will be conducted before each treatment for up to 3 weeks after each treatment session (treatment effect)
Comparison between the efficacy of sham, rTMS and H coil on average pain intensity over the course of the treatment
the average of pain scores (NRS for pain intensity) will be conducted before each treatment for up to 3 weeks after each treatment session (treatment effect)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Score of each neuropathic dimension (ie symptom combinations) on the Neuropathic pain symptom inventory (NPSI) (Bouhassira et al 2004) .
Time Frame: 1 week and 3 weeks after the end of each stimulation period
This validated questionnaire for neuropathic pain quantifies the mean intensity of 10 neuropathic symptoms and their combination into 5 distinct dimensions during the last 24 hours on 11-point (0-10) numerical scales.
1 week and 3 weeks after the end of each stimulation period
proportion of responders
Time Frame: 1 week and 3 weeks after the end of each stimulation period
proportion of patients achieving at least 30 % and 50 % pain relief as compared to prestimulation values allowing to calculate Numbers Needed to Treat for 30 % and 50 % pain relief.
1 week and 3 weeks after the end of each stimulation period
intensity of average pain
Time Frame: 1 week and 3 weeks after the end of each stimulation period
Numerical pain scale for average pain intensity from the the Brief Pain Inventory (BPI) rated from 0 (no pain) to 10 (maximal pain imaginable)
1 week and 3 weeks after the end of each stimulation period
Pain interference
Time Frame: 1 week and 3 weeks after the end of each stimulation period
7 items for pain interference of the BPI rated from 0 (does not interfere), to 10 (complete interference) to measure the impact of pain on general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life
1 week and 3 weeks after the end of each stimulation period
Hospital Anxiety and Depression Scale (HAD)
Time Frame: 1 week and 3 weeks after the end of each stimulation period
14 items scored as anxiety and depression scores (each on 21)
1 week and 3 weeks after the end of each stimulation period
French version of the Pain Catastrophizing Scale (PCS)
Time Frame: 1 week and 3 weeks after the end of each stimulation period
The PCS consists of 13 items describing the thoughts and feelings that individuals may experience when in pain (range 0-52); the patients' overall impression of change (PGIC) on a 7-point scale (from very much improved to very much worse).
1 week and 3 weeks after the end of each stimulation period
Intensity of maximal pain over the past 24 hours
Time Frame: 1 week and 3 weeks after the end of each stimulation period
Maximal pain intensity from the Brief Pain Inventory
1 week and 3 weeks after the end of each stimulation period
sensory and affective score of the short form McGill Pain questionnaire
Time Frame: 1 week and 3 weeks after the end of each stimulation period
15 items, of which 11 assess the sensory dimension of pain (rated on 44) and 4 assess the affective dimension of pain (rated on 15).
1 week and 3 weeks after the end of each stimulation period
Intensity of least pain over the past 24 hours
Time Frame: 1 week and 3 weeks after the end of each stimulation period
Intensity of least pain on NRS from the Brief Pain Inventory
1 week and 3 weeks after the end of each stimulation period
intensity of brush induced allodynia
Time Frame: 1 week and 3 weeks after the end of each stimulation period
measured with a brush (SOMEDIC) (mean of 3 stimulations) in the area of maximal pain on a 0-10 NRS
1 week and 3 weeks after the end of each stimulation period
side effects
Time Frame: immediately after each rTMS session
specific side effects questionnaire specifically designed for assessment of safety in rTMS studies
immediately after each rTMS session
blinding
Time Frame: 3 weeks after the end of the second stimulation period
blinding questionnaire
3 weeks after the end of the second stimulation period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Ambroise Paré Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Nadine ATTAL, Coordinator of the study

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 3, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 1, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HNEP4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

No plan to make individual participant data available to other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Central Pain Syndrome

Clinical Trials on rTMS

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings