Efficacy of rTMS Treatment After Spinal Cord Injury

Investigating the Efficacy of rTMS Treatment in Improving Motor Function After Spinal Cord Injury: A Placebo-controlled Study

There is accumulating evidence that neuromodulation by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex holds promise as a treatment for rehabilitation of motor function following a spinal cord injury. This study is designed to assess the clinical potential of non-invasive stimulation of the primary motor cortex to improve motor functions.The results will help to evaluate the clinical relevance of motor cortex stimulation for motor functions in patients with spinal cord injury. The outcomes of this study could potentially support the initiation of a larger clinical trial and the development of a new routine treatment.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries; Myelopathy
• Intervention / Treatment: Procedure: Placebo stimulation using a placebo coil; Procedure: Repetitive transcranial magnetic stimulation (rTMS)

Detailed Description

The investigators will recruit 20 patients with low cervical or thoracic ASIA C or D spinal cord injuries based on specific inclusion and exclusion criteria. The patients will be randomized into 2 groups. Each group will receive either the theta burst stimulation or the placebo stimulation. rTMS will be delivered using a figure-of-eight coil positioned on the patient's head, targeting the leg area of the primary motor cortex. After the motor threshold (MT) is determined patients will receive a unilateral 90% subthreshold theta burst stimulation for 3 minutes The protocol includes 15 stimulation sessions over a 3-week period. The 12-week follow up consist of a series of electrophysiological and functional tests to assess upper and lower limb function bilaterally. Secondary outcomes include pain using the NRS scale, and self-reported evaluation of autonomic functions before, during, and after the treatment.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mark Züchner, MD, PhD; Phone Number: +47 23070000; Email: mark.zuchner@medisin.uio.no

Study Locations

• Norway
  • Oslo, Norway, 0372
    • Recruiting
    • Oslo University Hospital - Rikshospitalet
    • Contact: Mark Züchner, MD, PhD; Phone Number: +4723070000; Email: mark.zuchner@medisin.uio.no
    • Contact: Jean-Luc Boulland, Assoc. Prof.; Phone Number: +4722851081; Email: j.l.boulland@medisin.uio.no
    • Sub-Investigator: Jean-Luc Boulland, Assoc.Prof.
    • Sub-Investigator: Rozan Albanna, MD
    • Sub-Investigator: Akif Yucesoy, MD cand.
    • Sub-Investigator: Eis Annavini, MSc, PhD
    • Sub-Investigator: Lars Etholm, MD, PhD
    • Sub-Investigator: Sara Maria Allen, MCs
    • Sub-Investigator: Bjørn-Erik Juel, MSc, PhD
    • Principal Investigator: Mark Züchner, MD, PhD
    • Sub-Investigator: Ana Isabel Reinartz Groba, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age over 18 years and less than 80 years
• Chronic patients with an incomplete cervical and/or thoracic spinal cord injury (traumatic and non-traumatic) affecting upper and/or lower extremities (i.e., C4-T12 and classified as ASIA C or D) (Figure 138).
• Capable and willing to provide informed consent and able to adhere to the treatment schedule
• Patients who can be followed for the whole duration of the study

6.3 Exclusion criteria

• Contraindication to rTMS:

  • past severe head trauma
  • history of epilepsy or ongoing epilepsy
  • active cerebral tumor
  • intracranial hypertension
  • implanted ferromagnetic devices such as cardiac pacemaker and neurostimulator and cochlear implants
  • pregnancy or lactation.
• Any clinically significant or unstable medical or psychiatric disorder
• Other ongoing research protocol or recent past protocol within two months before the inclusion
• History of treatment with Deep Brain Stimulation (DBS)
• Subjects protected by law (guardianship or tutelage measure)
• History of substance abuse (alcohol, drugs)
• Pending litigation
• Impossibility to understand the protocol or to fill out the forms
• Chronic use of sedative medication
• Participation in another clinical trial evaluating spinal cord injury

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo stimulation; Patients will receive stimulation from a placebo coil that only delivers skin tingling but no active brain stimulation.	Procedure: Placebo stimulation using a placebo coil; The placebo coil looks identical to the active coil but it only delivers skin tingling and no active brain stimulation.
Active Comparator: Active stimulation; Patients will receive active brain stimulation from a magnetic figure-of-eight-coil.	Procedure: Repetitive transcranial magnetic stimulation (rTMS); Intermittent Theta burst stimulation will be delivered on the on the primary motor cortex using a figure-of-eight coil, supported by neuronavigation. The stimulation intensity will be set to 90% of the motor threshold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor evoked potentials	Motor evoked potentials will be recorded at the start and the end of each stimulation session.	From enrollment to the end of follow up at 12 weeks
Global spasticity	Spasticity will be evaluated by using the modified Ashworth scale from 0 (no spasticity) to 4 (rigid extremities).	From enrollment to the end of follow-up at 12 weeks
Spasticity lower extremities	The Wartenberg pendulum is an objective test to assess the biomechanical properties of spasticity.The test consists of dropping the leg of a relaxed patient from a horizontal position and measuring oscillatory movements with a goniometer.	From enrollment to the end of follow-up at 12 weeks
Nine-Hole Peg Test	The Nine-Hole Peg Test is used to measure manual dexterity in patients with various neurological diagnoses. It is described in the literature to explore upper extremity function. Patients are asked to take nine pegs (7 mm diameter, 32 mm length) from a container (square box measuring 100 x 100 x 10 mm), one by one, and place them into the holes on the board, as quickly as possible. Scores are based on the time taken to complete the test activity, recorded in seconds.	From enrollment to the end of follow-up at 12 weeks
10-meter walking test	The 10-meter walk test (10MWT) is used to assess walking capabilities and walking speed in patients with gait impairments. Three trials will be recorded at the patient's fastest walking speed. The three trials are averaged and the gait speeds are documented in meters/second.	From enrollment to the end of follow-up at 12 weeks
Lower extremities kinematics	Movement kinematics will be extracted from recordings with 3D motion capture trackers that will record joint coordinates in time.	From enrollment to the end of follow-up at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric scale rating for pain evaluation	The analgesic efficacy of the stimulation protocol will be measured by the numeric scale rating (NRS), a self-reported measure in which patients rate their pain on a scale from 0 (no pain) to 10 (worst pain).	From enrollment to the end of follow-up at 12 weeks
European myelopathy score	The European myelopathy score is a reliable tool to assess functional recovery. The score ranges from 5 to 18. Higher values indicate better neurological function (outcome).	From enrollment to the end of follow-up at 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential adverse effect	In general, rTMS is a safe method. The use of exclusion criteria and ear plugs during stimulation will reduce side effects. Potential risks or side effects of rTMS include: Displacement of ferromagnetic device; Headache (3% in conventional rTMS studies) because of the noise generated by the stimulation; Seizures (0,16% in conventional rTMS studies) particularly in those with past epilepsy or brain surgery; Application site pain or discomfort and jaw pain	From enrollment to the end of follow-up at 12 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Study Chair: Bjørn Atle Bjørnbeth, MD,PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: rehabilitation; rTMS; spinal cord injury; motor cortex stimulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: 635283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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