Long-term Effects of Repetitive TMS in Chronic Neuropathic Pain in People With SCI

Around 80% of people with spinal cord injury (SCI) develop chronic neuropathic pain (CNP). This is a debilitating condition with major negative impacts on people's quality of life. Many treatment options have been offered (invasive stimulation, drugs) but provide limited effects and many secondary effects. There is a critical need to develop a new generation of therapies. Transcranial magnetic stimulation (TMS) is a non-invasive and painless brain stimulation technique that allows researchers to explore and change brain excitability that has shown promising effects in neuropathic pain. However there is not enough evidence of what are the long lasting effects of the different protocols. In this study, 30 SCI subjects with CNP in their hands will participate in the study. The objective is to evaluate the efficacy of real versus sham repetitive transcranial magnetic stimulation (rTMS) and investigate 1) short and long term effects on pain and 2) the behavioral and neurophysiological qualities of responders and non-responders to this treatment.This will be a randomized sham controlled trial with two groups: real or sham high frequency repetitive TMS protocol (20Hz). The protocol will be done daily for two weeks. Clinical, functional and neurophysiological evaluations will be assessed at baseline, post intervention and at 6-week follow up.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Pain; Neuralgia; Spinal Cord Injuries
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Abilities Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• presence of chronic neuropathic pain at or below SCI level for at least 6 months following trauma or disease of the spinal cord.
• cervical lesion.
• CNP in the upper extremity.
• pain intensity of at least 4 out of 10 in the numerical rating scale (NRS) in the NPS both screening (baseline) and randomization (pre-evaluation).both screening (baseline) and randomization (pre-evaluation).
• stable pharmacological treatment for at least 2 weeks prior to the study and throughout the trial.
• complete or incomplete lesion.

Exclusion criteria:

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: Real rTMS group; Repetitive TMS at 20Hz frequency over the M1 will be performed for five consecutive days for 2 weeks (using 90% of the resting motor threshold/total of 500 pulses). The rTMS will be applied through a figure-8 coil connected to a magnetic stimulator, which provides a biphasic pulse. This protocol was developed in accordance with the guidelines for the safe use of rTMS.	Device: Transcranial Magnetic Stimulation; Transcranial magnetic stimulation (TMS) is a non-invasive and painless brain stimulation technique that allows the brain excitability to change based on Faraday's Law of Electromagnetic induction . Since the presentation of the CNP is usually bilateral, the coil will be targeting the dominant hand abductor pollicis brevis (APB) muscle. If the pain is more intense in one of the arms, that arm will be targeted. This protocol was developed in accordance with the guidelines for the safe use of rTMS.
Sham Comparator: Sham group; Sham stimulation will be performed for five consecutive days for 2 weeks (using 90% of the resting motor threshold/total of 500 pulses). For the sham stimulation a sham coil will be used.	Device: Transcranial Magnetic Stimulation; Transcranial magnetic stimulation (TMS) is a non-invasive and painless brain stimulation technique that allows the brain excitability to change based on Faraday's Law of Electromagnetic induction . Since the presentation of the CNP is usually bilateral, the coil will be targeting the dominant hand abductor pollicis brevis (APB) muscle. If the pain is more intense in one of the arms, that arm will be targeted. This protocol was developed in accordance with the guidelines for the safe use of rTMS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain Scale (NPS)	This scale was developed to assess both the quantitative and qualitative qualities of NP. It includes 11 items, assessing global pain intensity, unpleasantness, and one item which allows the patient to describe the temporal aspects of their pain and its qualities in their own words. The remaining 8 items assess specific NP qualities: "Sharp," "Hot," "Dull," "Cold," "Sensitive," "Itchy," "Deep," and "Surface." This is a sensitive tool for measuring changes in neuropathic pain after a therapeutic intervention. Total scale from 0-10, with higher score indicating more pain.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS)	NRS to measure pain sensation, total score from 0-10, higher score indicates more intense pain.	6 weeks
Short-Form McGill Pain Questionnaire. (SF-MPQ)	The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or, 3 = severe. The SF-MPQ can be scored in several ways: a) number of words/descriptors chosen by the patient. Total scale from 0 to 45, with higher score indicating higher the pain experienced.	6 weeks
Present Pain Intensity (PPI) index	In the PPI index the adjectives/descriptors are ranked according to increasing intensity so each descriptor can be assigned a higher score: 0= no pain, 1=mild, 2=discomforting, 3= distressing, 4= horrible, 5= excruciating. Full range from 0 to 75, with higher score indicating higher intensity pain experienced.	6 weeks
Visual Analogue Scale (VAS)	The Visual Analogue Scale is the pain rating scale. Full scale from 0 to 10, with higher score indicating more pain.	6 weeks
The American Spinal Injury Association Impairment Scale (ASIA scale)	Upper extremity motor score (UEMS) will test the clinical motor strength from 0 to 5 of each key muscle using the ASIA scale in both arms. This sum score will range from 0 (paralyzed) to 25 (normal) in each limb (total of 50 bilaterally). Higher score indicates better health outcomes	6 weeks
Spinal cord independence measure (SCIM III)	Spinal cord independence measure (SCIM III) measures the ability of patients with SCI to perform everyday tasks. SCIM is used for quantitative functional outcome assessment following interventions designed to promote recovery from spinal cord injury and to increase functional achievement; it covers 19 tasks in 16 categories, with a total score range 0-100; all activities of daily living, grouped into four areas of function (subscales): Self-Care (scored 0-20), Respiration and Sphincter Management (0-40), Mobility in Room and Toilet (0-10), and Mobility Indoors and Outdoors (0-30). Higher score indicates better health outcomes.	6 weeks
Modified Ashworth Scale (MAS)	Modified Ashworth Scale (MAS) will measure changes in spasticity in the upper limbs after the stimulation period. For each upper limb, full Score range from 0 to 4, where lower. scores represent normal muscle tone and higher scores represent spasticity or increased resistance to passive movement.	6 weeks
Beck Depression Inventory (BDI)	This questionnaire is a 21-item, selfreport rating inventory that measures characteristic attitudes and symptoms of depression. Scoring is from 0 (minimal) to 3 (severe), with total score from 0-63. Higher total scores indicate more severe depressive symptoms.	6 weeks
Patient's Global Impression of Change (PGIC)	Full scale from 0-7, higher score indicates better health outcomes. he patients will answer the following question: "Since beginning treatment at this program, how would you describe the change (if any) in activity limitations, symptoms, emotions, and overall quality of life related to your condition?"	6 weeks
Resting Motor Threshold (RMT)	Using transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure RMT. Motor threshold is considered to reflect membrane-related intrinsic neuronal excitability.	6 weeks
Recruitment curve (RC)	Using transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure RC. The median amplitude at a given intensity is thought to represent trans-synaptic excitability of the corticospinal pathways.	6 weeks
Short intracortical inhibition (SICI)	Using transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure SICI. A single pulse TMS stimulus can be inhibited if preceded by a subthreshold conditioning stimulus 3 milliseconds apart. The SICI determines if changes in corticospinal output are related to altered intracortical excitability.	6 weeks
Silent period (SP):	Using transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure SP. During muscle contraction, the MEP is followed by a period of silent EMG activity. Changes in intracortical inhibition are reflected in altered SP duration.	6 weeks
Sensory threshold (ST):	Using a constant current electrical stimulator (Digitimer), sensory threshold can be quantified. It is defined as the weakest stimulus that can be detected.	6 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Mar Cortes, M.D., Icahn School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Chronic Pain; Transcranial Magnetic Stimulation; Spinal Cord Injuries; Neuropathic; Neural Plasticity
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Chronic Pain; Neuralgia; Spinal Cord Injuries
• Other Study ID Numbers: STUDY-20-00230; 19-1382-00001-01-PD (Other Grant/Funding Number: New York State Department Of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. For individual participant data meta-analysis. Proposals should be directed to mar.cortes@mountsinai.org. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be tbd).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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