Quantitative and Repetitive TMS in ALS - Recruiting for Stage 2

NCT05983211 | Recruiting

• 1 other identifier: QuARTS ALS
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety and Feasibility of cTBS rTMS in patients with ALS

  Incidence of AEs and SAEs after accelerated continuous theta burst stimulation inhibitory intervention in individuals with ALS through the incidence of repetitive TMS treatment related adverse events, serious adverse events, and discontinuations due to adverse events/serious adverse events.

  Up to 30 days before compared to during the initial 5 days of cTBS treatment and up to 24 weeks after

Secondary Outcomes (4)

• Neurofilament light chain (NfL) levels

  Up to 30 days before compared to the last treatment day, 12 weeks, and 24 weeks after cTBS treatment

• ALSFRS-R scores

  Up to 30 days before compared to 12 and 24 weeks after cTBS treatment

• Corticospinal Excitability change measured by quantitative TMS

  Up to 30 days before compared to 12 and 24 weeks after cTBS treatment

• Magnetic Resonance Spectroscopy parameters as measured by MRS

  Up to 30 days before compared to the end of treatment week, 5 weeks, 12 weeks, and 24 weeks after cTBS treatment

Study Arms (1)

Accelerated cTBS Neuromodulation

EXPERIMENTAL

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.

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic Stimulation 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.

Accelerated cTBS Neuromodulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Agessandro Abrahao, Dr.

  Sunnybrook Health Sciences Centre; University of Toronto

  PRINCIPAL INVESTIGATOR

• Lorne Zinman, Dr.

  Sunnybrook Health Sciences Centre; University of Toronto

  PRINCIPAL INVESTIGATOR

• Sean Nestor, Dr.

  Sunnybrook Research Institute; University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agessandro Abrahao, Dr.

CONTACT

(416) 480-6100; alsresearch@sunnybrook.ca

Jahan Mookshah

CONTACT

416 480-6100; jahan.mookshah@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Stage 1 \[Enrolment closed\]: A prospective, single-arm, open-label pilot trial evaluating the safety, feasibility and changes in neuronal excitability biomarkers of accelerated rTMS using cTBS inhibitory paradigms over M1 in patients with ALS Stage 2 \[CURRENTLY ENROLING\]: A prospective, single-arm, open-label pilot trial evaluating the safety, target engagement via biomarkers, and dose discovery of multi-targeted, accelerated continuous theta burst stimulation (cTBS) regimen of repetitive transcranial magnetic stimulation (rTMS) over multiple primary motor cortex (M1) regions bilaterally with repeated maintenance cTBS sessions for 24 weeks in patients with ALS.

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: August 9, 2023
• Study Start: May 1, 2024
• Primary Completion: April 15, 2026
• Study Completion (Estimated): April 15, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)