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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
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.
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
RECRUITINGSafety 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.
Time frame: Up to 30 days before compared to during the initial 5 days of cTBS treatment and up to 24 weeks after
Neurofilament light chain (NfL) levels
Change in concentration of serum neurofilaments from Baseline to Treatment, Week 12, and Week 24
Time frame: Up to 30 days before compared to the last treatment day, 12 weeks, and 24 weeks after cTBS treatment
ALSFRS-R scores
\>/= 6-point decline in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) scores from Baseline to Week 12 and Week 24. The ALSFRS-R measures functional ability in ALS with a minimum 0, maximum 48, and where a higher score means a better outcome.
Time frame: Up to 30 days before compared to 12 and 24 weeks after cTBS treatment
Corticospinal Excitability change measured by quantitative TMS
Change from baseline in Resting Motor Threshold (RMT), Cortical Silent Period (CSP), Short Intracortical Inhibition (SICI), and Short Intracortical Facilitation (SICF). All measurements use the same units.
Time frame: Up to 30 days before compared to 12 and 24 weeks after cTBS treatment
Magnetic Resonance Spectroscopy parameters as measured by MRS
Change from baseline in Glutamate, GABA, neuronal and redox metabolite ratios. All measurements use the same units.
Time frame: Up to 30 days before compared to the end of treatment week, 5 weeks, 12 weeks, and 24 weeks after cTBS treatment
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