Treatment of Peripheral Neuropathic Pain (BrainStim)

Deep Repetitive Transcranial Magnetic Stimulation for Peripheral Neuropathic Pain. A Randomized Double-blind Sham-controlled Study.

Peripheral neuropathic pain is a disabling chronic pain condition that is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) to the motor cortex is a treatment method with growing evidence in its ability to alleviate neuropathic pain. This also applies to new deep rTMS coils which permits stimulation of larger cortical areas and with deeper penetration. The aim of this study is to investigate the analgesic efficacy of 5 days of deep rTMS compared to sham stimulation. We will also assess effects of deep rTMS on sleep, psychological fatctors, everyday functioning, and executive functioning.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Device: repetitive Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadine Farnes, MSc; Phone Number: 0047 45243835; Email: nadine.farnes@gmail.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 18 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-80 years of age
• Peripheral neuropathic pain related to postherpetic neuralgia, peripheral nerve injury, limb amputation, polyneuropathy or radiculopathy, fulfilling the criteria for probable or definite neuropathic pain (Finnerup et al. 2016)
• Usual pain intensity at least 4/10 over the past 24 hrs using the numerical scale of the BPI at screening
• Daily pain
• Pain for at least 3 months
• Stable pharmacological treatment for pain or no pharmaceutical treatment at least 1 month prior to inclusion participation
• Ability to follow throughout the whole duration of the study

Exclusion Criteria:

atients with phantom limb pain after limb amputation

• Any clinically significant or unstable medical or psychiatric disorder
• Subjects protected by law (guardianship or tutelage measure)
• History of or current substance abuse (alcohol, drugs)
• Pending litigation
• Contraindication to rTMS (past severe head trauma, history of epilepsy or ongoing epilepsy, active cerebral tumour, past neurosurgical intervention, intracranial hypertension, implanted devices not compatible such as cardiac pacemaker and neurostimulator, cochlear implants, pregnancy or lactation. All women of childbearing age will be required to have negative pregnancy test at inclusion and to be using contraception)
• Pain conditions more severe than peripheral neuropathic pain
• Inability to understand the protocol or to fill out the forms
• Other ongoing research protocol or recent past protocol within one month before the inclusion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active and then sham rTMS; Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the arm.	Device: repetitive Transcranial Magnetic Stimulation; Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg.
Sham Comparator: Sham and the active rTMS; Sham stimulation is delivered with a sham coil placed in the helmet encasing the active rTMS coil. Sham rTMS sessions will use exactly the same parameters of stimulation as active rTMS.	Device: repetitive Transcranial Magnetic Stimulation; Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Usual pain intensity over the past 24 hours	Measured every day in a diary at the same hour (end of the day) on an 11-point NRS (0 = no pain, 10 = worst pain intensity imaginable of the current pain condition)	Analgesic efficacy of active and sham treatment is measured as the change in pain intensity scores between baseline values (one week before treatment) and 1 week after the last stimulation. Measurement ends 3 weeks after last stimulation]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Usual pain intensity over the past 24 hours	Measured every day in a diary at the same hour on an 11-point NRS (0 = no pain, 10 = worst pain intensity imaginable of the current pain condition)	Analgesic efficacy of active and sham treatment is measured as the change in pain intensity scores between baseline values and 3 weeks after the last stimulation
Pain intensity over the last 24 hours	Maximum and minimum pain intensity hours, rated from 0 (no pain) to 10 (pain as bad as you can imagine)	Baseline, 1 week and 3 weeks after the end of each stimulation period
Pain unpleasantness during the last 24 hours	Maximum, minimum, and usual pain unpleasantness, rated from 0 (no pain/unpleasantness) to 10 (unpleasantness as bad as you can imagine)	Baseline, 1 week and 3 weeks after the end of each stimulation period
Intensity of dynamic mechanical allodynia	Dynamic mechanical allodynia is assessed using a brush (SOMEDIC). The outcome is the mean pain intensity of 3 brush strokes within 2 seconds intervals. The length of the brush stroke is 3 cm, measured on an 11-point NRS (0 = no pain, 10 = worst pain intensity imaginable), disregarding the spontaneous ongoing pain.	Baseline, 1 week and 3 weeks after the end of each stimulation period
Intensity of static mechanical allodynia	Static mechanical allodynia is measured with a stimulus lightly indenting the skin for 10 seconds. The outcome is the mean pain intensity of three presses, measured on an 11-point NRS (0 = no pain, 10 = worst pain intensity imaginable), disregarding the spontaneous ongoing pain.	Baseline, 1 week and 3 weeks after the end of each stimulation period
Proportion of responders	Proportion of responders with at least 30% and 50% usual pain intensity reduction compared to prestimulation values allowing to calculate Numbers Needed to Treat for 30 % and 50 % pain relief.	Baseline,1 week and 3 weeks after the end of each stimulation period]
Percentage pain intensity reduction	Percentage pain intensity reduction on an 11-point NRS (0 %= no pain reduction; 100% complete pain reduction)	Baseline,1 week and 3 weeks after the end of each stimulation period
Hospital Anxiety and Depression Scale	The Hospital Anxiety and Depression Scale includes 14 items scored as anxiety and depression scores, 7 items assessing depression and 7 anxiety	Baseline,1 week and 3 weeks after the end of each stimulation period
Pain Catastrophizing Scale	Consists of 13 items describing the occurrence of thoughts and feelings that individuals may experience when in pain rated from 0 (not at all) to 4 (all the time)	Baseline,1 week and 3 weeks after the end of each stimulation period
Patient Global Impression of Change	Consists of 7 items to evaluate the subjective improvement or deterioration (from very much improved to very much deteriorated)	Baseline,1 week and 3 weeks after the end of each stimulation period
Insomnia Severity Index	Consists of self-rated questions which maps sleep difficulties specific to insomnia on a 5 point Likert scale	Baseline,1 week and 3 weeks after the end of each stimulation period
Patient-Specific Functional Scale	The Patient-Specific Functional Scale is a numeric rating scale that measures individually chosen functions that are inhibited by the pain. Patients rate from 0 (unable to perform activity) to 10 (able to perform activity)	Baseline,1 week and 3 weeks after the end of each stimulation period
Executive functioning using the CANTAB battery	Composite score and individual analyses of the paired associates learning test, stop signal task, spatial working memory test and the multitasking test weeks after the end of each stimulation period	Baseline,1 week and 3 weeks after the end of each stimulation period
Side-effects	Side effects using a specific side effects questionnaire specifically designed for assessment of safety in rTMS studies	Immediately after the first rTMS session for both stimulation periods and 1 week and 3 weeks after each stimulation period
Blinding	Blinding questionnaire	3 weeks after the end of each stimulation period

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Study Director: Audun Stubhaug, MD, PhD, OUS

Publications and helpful links

General Publications

• Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): November 24, 2023
• Study Completion (Actual): November 24, 2023

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Repetitive Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 428116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified individual participant data collected during the trial will be available to other researchers who provide a methodologically sound proposal, and who adhere to institutional guidelines.

Drug and device information, study documents

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