Central Pain SyndromeHNEPNCT03370107
Comparison of rTMS and H Coil in Neuropathic Pain
A study testing rTMS in people with Central Pain Syndrome, run by Hospital Ambroise Paré Paris at 1 site in Norway.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Central Pain Syndrome
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteNorway
- Study dates
- 3 Jan 2018to 30 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Norway1 site
Department of Pain Management and Research, Oslo University Hospital and Faculty of Medicine, University of Oslo, Norway
Oslo, 0424
About this study
Official title: 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
Read the 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.
- Conditions
- Central Pain Syndrome
- Being tested
- rTMS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS and H coil | Active comparator | Not described Receives: Device: rTMS |
| sham rTMS and Hcoil | Placebo comparator | Not described Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Comparison between the efficacy of sham, rTMS and H coil on average pain intensity over the course of the treatment
Measured: 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 outcomes (12)
Score of each neuropathic dimension (ie symptom combinations) on the Neuropathic pain symptom inventory (NPSI) (Bouhassira et al 2004) .
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.
Measured: 1 week and 3 weeks after the end of each stimulation period
proportion of responders
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.
Measured: 1 week and 3 weeks after the end of each stimulation period
intensity of average pain
Numerical pain scale for average pain intensity from the the Brief Pain Inventory (BPI) rated from 0 (no pain) to 10 (maximal pain imaginable)
Measured: 1 week and 3 weeks after the end of each stimulation period
Pain interference
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
Measured: 1 week and 3 weeks after the end of each stimulation period
Hospital Anxiety and Depression Scale (HAD)
14 items scored as anxiety and depression scores (each on 21)
Measured: 1 week and 3 weeks after the end of each stimulation period
French version of the Pain Catastrophizing Scale (PCS)
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).
Measured: 1 week and 3 weeks after the end of each stimulation period
Intensity of maximal pain over the past 24 hours
Maximal pain intensity from the Brief Pain Inventory
Measured: 1 week and 3 weeks after the end of each stimulation period
sensory and affective score of the short form McGill Pain questionnaire
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).
Measured: 1 week and 3 weeks after the end of each stimulation period
Intensity of least pain over the past 24 hours
Intensity of least pain on NRS from the Brief Pain Inventory
Measured: 1 week and 3 weeks after the end of each stimulation period
intensity of brush induced allodynia
measured with a brush (SOMEDIC) (mean of 3 stimulations) in the area of maximal pain on a 0-10 NRS
Measured: 1 week and 3 weeks after the end of each stimulation period
side effects
specific side effects questionnaire specifically designed for assessment of safety in rTMS studies
Measured: immediately after each rTMS session
blinding
blinding questionnaire
Measured: 3 weeks after the end of the second stimulation period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2017
- Study start3 Jan 2018
- Primary completion30 Oct 2021
- Study completion30 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Pain SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Ambroise Paré Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nadine ATTAL, Hospital Ambroise Paré Paris
- Investigators
- Nadine ATTAL, Study director, Coordinator of the study
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03370107
- Sponsor's protocol ID
- HNEP4
- Acronym
- HNEP
- Status last verified
- Oct 2022
- First submitted
- 1 Dec 2017
- Last updated
- 17 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: No plan to make individual participant data available to other researchers
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03370107
- Acronym / sponsor ID
- HNEP / HNEP4
- Conditions
- Central Pain Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Hospital Ambroise Paré ParisUniversity, hospital or other
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Oct 2021 (actual)
- First posted
- 12 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients 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).
| Arm | Type | Receives |
|---|---|---|
| Active rTMS and H coil | Active comparator | Device: rTMS |
| sham rTMS and Hcoil | Placebo comparator | Device: rTMS |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- Any clinically significant or unstable medical or psychiatric disorder
- History of substance abuse
- Litigation
- Pregnancy/lactation
- Contraindication to rTMS or Hcoil
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMSConventional 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. | Device | Active rTMS and H coil, sham rTMS and Hcoil |
Primary outcome
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
12 secondary outcomes
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
proportion of responders
Time frame: 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
Pain interference
Time frame: 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
French version of the Pain Catastrophizing Scale (PCS)
Time frame: 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
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
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 brush induced allodynia
Time frame: 1 week and 3 weeks after the end of each stimulation period
side effects
Time frame: immediately after each rTMS session
blinding
Time frame: 3 weeks after the end of the second stimulation period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2022.
- Individual participant dataSharing planned: Undecided. No plan to make individual participant data available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nadine ATTAL study director
Coordinator of the study
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Central Pain Syndrome, run by Hospital Ambroise Paré Paris at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2022.