Quantitative and Repetitive TMS in ALS - Recruiting for Stage 2

NCT ID: NCT05983211

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2027-04-15

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.

Detailed Description

Stage 1 [Enrolment closed]:

The purpose of this stage is to evaluate the safety, feasibility, and changes in neuronal excitability biomarkers of accelerated repetitive transcranial magnetic stimulation (rTMS) using continuous theta-burst stimulation (cTBS) inhibitory paradigms over M1 in patients with ALS.

Stage 2 [CURRENTLY ENROLLING]:

The purpose of this study is to:

1. Assess the safety and feasibility of accelerated cTBS treatment with maintenance cTBS treatments in individuals with ALS over a 24-week period.

2. Assess changes in MR spectroscopy measures of glutamate and GABA, ATP and metabolites markers, and neuronal structure markers, changes in serum neurofilament light chain, and changes in corticohyperexcitability biomarkers measured by single and paired pulse quantitative TMS.

3. Assess the changes in ALSFRS-R and muscle strength dynamometry.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

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.

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.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agessandro Abrahao, Dr.

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre; University of Toronto

Lorne Zinman, Dr.

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre; University of Toronto

Sean Nestor, Dr.

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Research Institute; University of Toronto

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Agessandro Abrahao, Dr.

Role: CONTACT

alsresearch@sunnybrook.ca

(416) 480-6100 ext. 687561

Jahan Mookshah

Role: CONTACT

jahan.mookshah@sunnybrook.ca

416 480-6100 ext. 687561

Facility Contacts

Agessandro Abrahao, Dr

Role: primary

alsresearch@sunnybrook.ca

(416) 480-6100 ext. 687561

Jahan Mookshah

Role: backup

jahan.mookshah@sunnybrook.ca

(416) 480-6100 ext. 687561

Other Identifiers

QuARTS ALS

Identifier Type: -

Identifier Source: org_study_id