Accelerated repetitive transcranial magnetic stimulation for ALS

A Biomarker-Directed Neuromodulation Trial Using Quantitative and Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis (The QuARTS-ALS Trial)

This study is testing a new type of brain stimulation to see if it can help people with ALS feel better and improve their muscle strength over 24 weeks.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT05983211 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety, tolerability, and effectiveness of accelerated, high-dose continuous theta-burst stimulation (cTBS) using repetitive transcranial magnetic stimulation (rTMS) in patients diagnosed with amyotrophic lateral sclerosis (ALS). The study will assess changes in neuronal excitability biomarkers, including glutamate and GABA levels, over a 24-week treatment period. Participants will also undergo assessments of muscle strength and overall ALS function using standardized scales. The trial is currently enrolling participants who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with ALS who can provide informed consent and do not have contraindications to TMS.

Not a fit: Patients with severe respiratory issues requiring BiPAP or those with contraindications to TMS, such as certain metal implants or a history of epilepsy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option to improve neuronal function and quality of life for patients with ALS.

How similar studies have performed: While this approach is novel in the context of ALS, previous studies using TMS have shown promise in other neurological conditions, suggesting potential for success.

Eligibility criteria

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.

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Agessandro Abrahao, Dr. — Sunnybrook Health Sciences Centre; University of Toronto
• Study coordinator: Agessandro Abrahao, Dr.

Conditions Amyotrophic Lateral Sclerosis; ALS; Repetitive transcranial magnetic stimulation; Corticospinal Excitability; Motor Neuron Disease; MR Spectroscopy; Cortical Hyperexcitability