Analgesic Effect of rTMS in Vasculitic Neuropathy

Analgesic Effect of Repetitive Transcranial Magnetic Stimulation in Painful Vasculitic Neuropathy

Vasculitic neuropathy (VN) results from inflammation and destruction of the walls of predominantly small vessels with subsequent ischemic damage of peripheral nerves. VN is painful in vast majority of patients and the pain is intractable with pharmacotherapy in about 40% of cases. 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. The purpose of this study is to compare the effectiveness of analgesic effect of rTMS in vasculitic neuropathy with sham stimulation.

Study Overview

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

Detailed Description

Vasculitic neuropathies (VN) are a group of disorders resulting from inflammation of predominantly small vessels with destruction of their walls and subsequent ischemic damage of peripheral nerves. Neural damage may or may not coexist with the damage of other organs. Examples of conditions associated with VN include diabetes, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, systemic lupus erythematosus and others. VN is painful in about 80% of patients of whom 40% suffer from the pain intractable with pharmacological therapy. 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 widely regarded as one of alternative methods to alleviate pain associated with various kind of neuropathies. The purpose of this study is to compare the effectiveness of analgesic effect of rTMS in vasculitic neuropathy with sham stimulation.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• 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].edu.pl

Study Locations

• Poland
  • Kraków, Poland, 31503
    • Recruiting
    • Jagiellonian University Medical College, Department of Neurology
    • Contact: Jakub M Antczak, MD; Phone Number: +48 795 421 153; Email: [email protected]
    • Contact: Gabriela Rusin, MD; Phone Number: +48 601 661 607; Email: [email protected]
    • Sub-Investigator: Justyna Brączyk, MS

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 vasculitic 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 milimeter or more on the 100 milimeter 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
• Contraindications for rTMS as listed by the Guidelines of the International Federation of Clinical Neurophysiology (Rossi et al. 2009) i.e. seizure in the past, epilepsy, presence of magnetic material in the reach of magnetic field, pregnancy, likelihood to get pregnant, intracranial electrodes, cardiac pacemaker or intracardiac lines, frequent syncopes

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
Experimental: Active repetitive transcranial magnetic stimulation; 10 hertz (Hz) rTMS will be administered over the primary motor area. Therapy will include 5 daily sessions (on consecutive week 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.

What is the study measuring?

Primary 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, immediately after (on same day) 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 four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Visual Analog Scale of Pain Severity	An analog scale of the length of 100 milimeter. Total score of 100, with higher scores representing more severe pain. Change through the study.	Through study completion, an average of 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale after rTMS	Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Hospital Anxiety and Depression Scale First Follow Up	Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Hospital Anxiety and Depression Scale Second Follow Up	Total score 64, with higher scores representing more severe depression. Change from baseline score in the Hospital Anxiety and Depression Scale to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
36-Item Short Form Health Survey after rTMS	Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
36-Item Short Form Health Survey First Follow Up	Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
36-Item Short Form Health Survey Second Follow Up	Total score, range 0 to 800, with lower values representing a worse outcome. Change from baseline score in the 36-Item Short Form Health Survey to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function after rTMS	Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function First Follow Up	Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function Second Follow Up	Total score, range 0 to 100, with lower values representing a worse outcome. Change from baseline score in Neuro-Qol Upper Extremity Function to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of pain threshold to electric stimuli after rTMS	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of sensory threshold to electric stimuli after rTMS	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of pain threshold to electric stimuli First Follow Up	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of sensory threshold to electric stimuli First Follow Up	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of pain threshold to electric stimuli Second Follow Up	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports that the sensation has become painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of sensory threshold to electric stimuli Second Follow Up	Electrocutaneus stimulation with gradually increasing intensity from 0mA until a patient reports the first nonpainful tactile sensation. Change from baseline sensory threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of cold sensation threshold to cold stimuli after rTMS	Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of pain threshold to cold temeprature stimuli after rTMS	Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of cold sensation threshold to cold temeprature stimuli First Follow Up	Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of pain threshold to cold temeprature stimuli First Follow Up	Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of cold sensation threshold to cold temeprature stimuli Second Follow Up	Stimulation with cold temperature stimuli, gradually colder, starting from from 32 degree Celcius until patient will report that he feels cold. Change from baseline cold sensation threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of pain threshold to cold temeprature stimuli Second Follow Up	Stimulation with cold temperature stimuli, gradually colder, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of warmth sensation threshold to warm temeprature stimuli after rTMS	Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of pain threshold to warm temeprature stimuli after rTMS	Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) finishing rTMS.
Assessment of warmth sensation threshold to warm temeprature stimuli First Follow Up	Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of pain threshold to warm temeprature stimuli First Follow Up	Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken two weeks after finishing rTMS.	Before rTMS, two weeks after finishing rTMS
Assessment of warmth sensation threshold to warm temeprature stimuli Second Follow Up	Stimulation with warm temperature stimuli, gradually warmer, starting from from 32 degree Celcius until patient will report that he feels warmth. Change from baseline warmth sensation threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Assessment of pain threshold to warm temeprature stimuli Second Follow Up	Stimulation with warm temperature stimuli, gradually warmer, starting from 32 degree Celcius until patient starts to perceive stimuli as painful. Change from baseline pain threshold to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS
Bilateral Dynamometric Assessment of the strength of the index finger flexion after rTMS	Change from baseline strength of the index finger flexion to the measurement taken after finishing rTMS.	Before rTMS, immediately after (on same day) 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, immediately after (on same day) finishing rTMS.
Bilateral Dynamometric Assessment of the strength of the index finger flexion First Follow Up	Change from baseline strength of the index finger flexion 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 flexion 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 index finger flexion Second Follow Up	Change from baseline strength of the index finger flexion 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 Second Follow Up	Change from baseline strength of the index foot extension to the measurement taken four weeks after finishing rTMS.	Before rTMS, four weeks after finishing rTMS

Collaborators and Investigators

• Sponsor: Jagiellonian University
• Investigators: Study Chair: Justyna Brączyk, MS, Jagiellonian University

Publications and helpful links

General Publications

• Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: January 16, 2021
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: pain; transcranial magnetic stimulation; neuropathy; vasculitis; analgesic effect
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: JagiellonianU63

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 send by e-mail: [email protected]
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; 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