Amyotrophic Lateral SclerosisQuARTS-ALSNCT05983211
Quantitative and Repetitive TMS in ALS - Recruiting for Stage 2
A study testing Repetitive Transcranial Magnetic Stimulation in people with Amyotrophic Lateral Sclerosis, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2024to 15 Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Agessandro Abrahao, Dr, (416) 480-6100 ext. 687561, alsresearch@sunnybrook.ca
Jahan Mookshah, (416) 480-6100 ext. 687561, jahan.mookshah@sunnybrook.ca
About this study
Official title: A Biomarker-Directed Neuromodulation Trial Using Quantitative and Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis (The QuARTS-ALS Trial)
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.
Read the 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:
- Assess the safety and feasibility of accelerated cTBS treatment with maintenance cTBS treatments in individuals with ALS over a 24-week period.
- 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.
- Assess the changes in ALSFRS-R and muscle strength dynamometry.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Repetitive Transcranial Magnetic Stimulation
- Keywords
- ALS, Repetitive transcranial magnetic stimulation, Corticospinal Excitability, Motor Neuron Disease, MR Spectroscopy, Cortical Hyperexcitability
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Change in concentration of serum neurofilaments from Baseline to Treatment, Week 12, and Week 24
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 30 days before compared to the end of treatment week, 5 weeks, 12 weeks, and 24 weeks after cTBS treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2023
- Study start1 May 2024
- Primary completion15 Apr 2026 (estimated)
- Study completion15 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agessandro Abrahao, Dr., Principal investigator, Sunnybrook Health Sciences Centre; University of TorontoLorne Zinman, Dr., Principal investigator, Sunnybrook Health Sciences Centre; University of TorontoSean Nestor, Dr., Principal investigator, Sunnybrook Research Institute; University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05983211
- Sponsor's protocol ID
- QuARTS ALS
- Acronym
- QuARTS-ALS
- Status last verified
- Aug 2024
- First submitted
- 11 Jul 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Biomarker-Directed Neuromodulation Trial Using Quantitative and Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis (The QuARTS-ALS Trial)
- ClinicalTrials.gov ID
- NCT05983211
- Acronym / sponsor ID
- QuARTS-ALS / QuARTS ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Repetitive transcranial magnetic stimulation, Corticospinal Excitability, Motor Neuron Disease, MR Spectroscopy, Cortical Hyperexcitability
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 1 May 2024 (actual)
- Primary completion
- 15 Apr 2026 (estimated)
- Study completion
- 15 Apr 2027 (estimated)
- First posted
- 9 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Assess the safety and feasibility of accelerated cTBS treatment with maintenance cTBS treatments in individuals with ALS over a 24-week period.
- 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.
- Assess the changes in ALSFRS-R and muscle strength dynamometry.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Accelerated cTBS Neuromodulation | Experimental | Device: Repetitive Transcranial Magnetic StimulationStage 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationStage 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. | Device | Accelerated cTBS Neuromodulation |
Primary outcome
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
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.
4 secondary outcomes
Neurofilament light chain (NfL) levels
Time frame: Up to 30 days before compared to the last treatment day, 12 weeks, and 24 weeks after cTBS treatment
ALSFRS-R scores
Time frame: Up to 30 days before compared to 12 and 24 weeks after cTBS treatment
Corticospinal Excitability change measured by quantitative TMS
Time frame: Up to 30 days before compared to 12 and 24 weeks after cTBS treatment
Magnetic Resonance Spectroscopy parameters as measured by MRS
Time frame: Up to 30 days before compared to the end of treatment week, 5 weeks, 12 weeks, and 24 weeks after cTBS treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Agessandro Abrahao, Dr. principal investigator
Sunnybrook Health Sciences Centre; University of Toronto
Lorne Zinman, Dr. principal investigator
Sunnybrook Health Sciences Centre; University of Toronto
Sean Nestor, Dr. principal investigator
Sunnybrook Research Institute; University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation in people with Amyotrophic Lateral Sclerosis, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agessandro Abrahao, Dr. ((416) 480-6100 ext. 687561, alsresearch@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.