Recruiting

TMS

Sponsor:

Sunnybrook Health Sciences Centre

Code:

NCT05983211

Conditions

Amyotrophic Lateral Sclerosis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Repetitive Transcranial Magnetic Stimulation

Study Details

Brief summary:

Stage 1 \[Enrolment closed\]:

The goal of this open-label pilot clinical trial is to evaluate the safety and feasibility of accelerated, repetitive transcranial magnetic stimulation (rTMS) using continuous theta-burst stimulation (cTBS) in patients with ALS.

Stage 2 \[CURRENTLY ENROLLING\]:

The goal of this open-label pilot clinical trial is to evaluate the safety, tolerability and target engagement of accelerated, high dose cTBS using TMS in patients with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Study ID

NCT05983211

Start date

May 1, 2024

Status verified date

Aug, 2024

Completion date

Apr 15, 2027

Anticipated

Primary completion date

Apr 15, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Diagnosis with ALS as per the 2020 Gold Coast Criteria;
  • Age ≥ 18 years;
  • Able to provide informed consent to study procedures and treatments;
  • Patients are allowed to start or continue the standard of care treatments for ALS. Presently these include oral riluzole, and oral or intravenous edaravone;
  • Able to lie supine without BiPAP or breathing discomfort for at least 1 hour;
  • No contraindications to TMS as follow;
  • Metal implants in the head or neck (such as aneurysm clips, vessel stents), implanted medication pump, implanted brain stimulators, pacemaker, cochlear implants, or history of epilepsy. Dental fillings are permitted;
  • Current use of medications or medical conditions that, at the discretion of the Principal Investigator, could potentially increase the risk of seizures or interfere with stage outcomes;
  • On medications that affect TMS measures in a PRN regimen (as needed). Continuous use of these medications on a fixed dose of 30 days prior to first Baseline Visit or after a wash-out period of 2 weeks is accepted. These medications include, but are not limited to: benzodiazepines, muscle relaxants, tricyclic antidepressants, selective and non-selective serotonin reuptake inhibitors, hypnotics (including anti-histamine drugs) and anticholinergics drugs;
  • History of seizure, convulsion, or epilepsy;

Exclusion Criteria:

  • Known diagnosis of dementia;
  • Definitely or possibly pregnant (if applicable);
  • History of allergy to Ag-AgCl electrode gel (standard neurophysiology electrodes);
  • Unable to tolerate TMS procedures;
  • Lack of MRI brain performed prior to the stage, inability to perform an MRI at baseline due to orthopnea, or:
  • Large body habitus and not fitting comfortably into the scanner;
  • Difficulty laying still for up to 1 hour in the MRI unit or significant claustrophobia;
  • Metallic implants;
  • Any contraindications for receiving rTMS treatment as follow:
  • have received rTMS for any previous indication due to the potential compromise of subject blinding;
  • have increased intracranial pressure, a space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, significant head trauma with clear radiological evidence of cerebrovascular injury on imaging;
  • have an intracranial implant or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
  • have clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians;
  • are currently taking more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy;
  • Any other clinical condition that, in the opinion of the Site Investigator, would place the subject at increased risk or preclude the subject's full compliance with completion of the stage.

Study Design

Enrollment

15 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Accelerated cTBS Neuromodulation

Stage 2 \[CURRENTLY ENROLLING\]:

ALS patients receiving an accelerated schedule of continuous theta burst rTMS bilaterally at multiple M1 regions at a regimen of 40 seconds, 1 minute 20 seconds, 2 minutes, or 4 minutes per treatment for up to 8 treatment sessions per day, delivered one per hour, over 5 days. Additional single-day maintenance treatments will follow these 5 days at a frequency of every 2 weeks for 12 weeks, then every 4 weeks for 12 weeks.

Interventions

Repetitive Transcranial Magnetic Stimulation

Stage 2 \[CURRENTLY ENROLLING\]:

Accelerated rTMS using continuous theta burst stimulation (cTBS) inhibitory paradigms over bilateral M1 including hand, leg, and bulbar regions outputted at 90% of resting motor threshold, using bursts of 3 pulses at 50 Hz. Bursts are repeated at 5 Hz for a total of 600, 1200, 1800, or 3600 pulses over 40 seconds, 1 minute 20 seconds, 2 minutes, or 4 minutes. ALS patients will receive rTMS bilaterally for up to 8 treatment sessions per day, delivered one per hour, over 5 days, followed by single-day maintenance treatments at a frequency of every 2 weeks for 12 weeks, then every 4 weeks for 12 weeks.

Primary outcome measure

  • Safety and Feasibility of cTBS rTMS in patients with ALS [ Time Frame: Up to 30 days before compared to during the initial 5 days of cTBS treatment and up to 24 weeks after ]

Central Contacts and Locations

Central contacts

Agessandro Abrahao, Dr.

(416) 480-6100alsresearch@sunnybrook.ca

Jahan Mookshah

416 480-6100jahan.mookshah@sunnybrook.ca

Locations

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Agessandro Abrahao, Dr

(416) 480-6100alsresearch@sunnybrook.ca

Jahan Mookshah

(416) 480-6100jahan.mookshah@sunnybrook.ca

Principal Investigator:

Agessandro Abrahao, Dr

More Information

Sponsor

Sunnybrook Health Sciences Centre

Last update posted

Sep 19, 2024

Last verified

Aug, 2024

Keywords

  • ALS
  • Repetitive transcranial magnetic stimulation
  • Corticospinal Excitability
  • Motor Neuron Disease
  • MR Spectroscopy
  • Cortical Hyperexcitability

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sunnybrook Health Sciences Centre on 2024-09-19.