Analgesic Effect of Accelerated Repetitive Transcranial Magnetic Stimulation in Neuropathic Pain

Analgesic Effect of Accelerated Repetitive Transcranial Magnetic Stimulation in Pain Related to Peripheral Neuropathy

Peripheral neuropathy is a frequent condition, commonly associated with pain. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity and is regarded as one of alternative methods to alleviate pain associated with various kind of neuropathies. rTMS is usually performed once a day and the whole therapy of neuropathic pain lasts one week. In a number of recent clinical trials including patients with depression and some other disorders, rTMS was delivered several times a day, which reduced the time of the whole therapy. This approach was termed an accelerated rTMS. The purpose of this study is to investigate feasibility of accelerated rTMS in treatment of neuropathic pain.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Neuropathy
• Intervention / Treatment: Device: Active repetitive transcranial magnetic stimulation; Device: Sham repetitive transcranial magnetic stimulation

Detailed Description

Peripheral neuropathy is a frequent condition, commonly associated with pain, which is often drug resistant. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity. In this method, series of magnetic stimuli are delivered to the cerebral cortex, where they turn to electric current and depolarize repetitively the targeted neurons. If the stimulation is repeated during subsequent days it is capable to modify the activity of targeted cortical area for weeks or even months and by this way to achieve therapeutic effect. rTMS is most commonly used to treat drug-resistant depression but a number of other psychiatric and neurologic conditions is increasingly being regarded as therapeutic indication for rTMS. In patients suffering from neuropathic pain rTMS is delivered with high frequency, over primary motor areas (PMA). Stimulation of PMA should result in modulation of thalamic activity, achieved by antidromic excitation of thalamocortical connections. rTMS is usually performed once a day and the whole therapy of neuropathic pain lasts one week. In a number of recent clinical trials including patients with depression and some other disorders, rTMS was delivered several times a day, which reduced the time of the whole therapy. This approach was termed an accelerated rTMS. The purpose of this study is to investigate feasibility of accelerated rTMS in treatment of neuropathic pain.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jakub M Antczak, MD; Phone Number: +48 795 421 153; Email: [email protected]
• Study Contact Backup: Name: Gabriela G Rusin, MD; Phone Number: +48 601 661 607; Email: [email protected]

Study Locations

• Poland
  • Kraków, Poland, 31008
    • Recruiting
    • Jagiellonian University Medical College
    • Contact: Jakub Antczak, MD; Email: [email protected]

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of peripheral neuropathy
• Neuropathic pain of constant severity since not less than a month and requiring use of analgesics more than once a week
• Score of 30 millimeter or more on the 100 millimeter visual analog scale of pain intensity at inclusion

Exclusion Criteria:

• Severe depression
• Personality disorders and other psychiatric conditions, which could disturb the participation in the study
• Cognitive deficits, which could disturb the participation in the study
• Epilepsy
• Presence of magnetic material in the reach of magnetic field
• Pregnancy
• Likelihood to get pregnant
• Intracranial electrodes

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active repetitive transcranial magnetic stimulation; 10 hertz (Hz) rTMS will be administered over the primary motor area. Therapy will include 6 sessions (three sessions in two consecutive days). In every sessions 1500 magnetic pulses of 90% of the resting motor threshold intensity will be elicited.	Device: Active repetitive transcranial magnetic stimulation; High frequency rTMS over the primary motor area to induce the long term potentiation of primary motor areas for the muscles of upper extremity.
Sham Comparator: Sham repetitive transcranial magnetic stimulation; Sham stimulation will mimic the active one except that the stimulating coil will be held perpendicularly to the scalp, which assures similar impression as the active stimulation but prevents that significant magnetic field will reach brain tissue.	Device: Sham repetitive transcranial magnetic stimulation; Sham stimulation to mimic the high frequency rTMS over the primary motor area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale of Pain Severity after rTMS	An analog scale of the length of 100 millimeter. Total score of 100, with higher scores representing more severe pain. Change from baseline score in the Visual Analogue Scale to the measurement taken after finishing rTMS.	Through study completion, an average of 1 year.
Visual Analogue Scale of Pain Severity First Follow-up	An analog scale of the length of 100 millimeter. Total score of 100, with higher scores representing more severe pain. Change from baseline score in the Visual Analogue Scale to the measurement taken after two weeks after finishing rTMS.	Before rTMS, up to one day after finishing rTMS.
Visual Analogue Scale of Pain Severity Second Follow-up	An analog scale of the length of 100 millimeter. Total score of 100, with higher scores representing more severe pain. Change from baseline score in the Visual Analogue Scale to the measurement taken after four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Pain Severity Scale after rTMS	Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken after finishing rTMS.	Before rTMS, up to one day after finishing rTMS.
Numeric Pain Severity Scale First Follow-up	Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS.
Numeric Pain Severity Scale Second Follow-up	Total score 10, with higher scores representing more severe pain. Change from baseline score in the Numeric Pain Severity Scale to the measurement taken after four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS.
Neuropathic Pain Symptoms Inventory after rTMS	Total score 120, with higher scores representing more severe pain and other symptoms of neuropathy. Change from baseline score in the Neuropathic Pain Symptoms Inventory to the measurement taken after finishing rTMS.	Before rTMS, up to one day after finishing rTMS.
Neuropathic Pain Symptoms Inventory First Follow-up	Total score 120, with higher scores representing more severe pain and other symptoms of neuropathy. Change from baseline score in the Neuropathic Pain Symptoms Inventory to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS.
Neuropathic Pain Symptoms Inventory Second Follow-up	Total score 120, with higher scores representing more severe pain and other symptoms of neuropathy. Change from baseline score in the Neuropathic Pain Symptoms Inventory to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS.
Athens Insomnia Scale after rTMS	Total score 24, with higher scores representing more severe insomnia. Change from baseline score in the Athens Insomnia Scale to the measurement taken after finishing rTMS.	Before rTMS, up to one day after finishing rTMS.
Athens Insomnia Scale First Follow-up	Total score 24, with higher scores representing more severe insomnia. Change from baseline score in the Athens Insomnia Scale to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS.
Athens Insomnia Scale Second Follow-up	Total score 24, with higher scores representing more severe insomnia. Change from baseline score in the Athens Insomnia Scale to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS.
Bilateral Dynamometric Assessment of the strength of the foot extension after rTMS	Change from baseline strength of the foot extension to the measurement taken after finishing rTMS.	Before rTMS, up to one day after finishing rTMS.
Bilateral Dynamometric Assessment of the strength of the foot extension First Follow-up	Change from baseline strength of the foot extension to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS.
Bilateral Dynamometric Assessment of the strength of the foot extension Second Follow-up	Change from baseline strength of the foot extension to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS.

Collaborators and Investigators

• Sponsor: Jakub Antczak
• Investigators: Study Chair: Tomasz Klupa, Professor, Jagiellonian University

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 16, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Neuropathic pain; rTMS; Peripheral neuropathy; analgesic effect
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: JagiellonianU69

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After completing the study, the age and gender of participants as well as the scores and results of all outcome measurements made at baseline, after rTMS, at the first and at the second follow-up will be made available to other researchers on request.
• IPD Sharing Time Frame: The data will become available after the study results will be published.
• IPD Sharing Access Criteria: On request sent by e-mail to [email protected]
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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