Amyotrophic Lateral SclerosisNCT03664206
Assessing Motor Neuron Disease Mechanisms by Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
An observational study of Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by Sándor Beniczky at 1 site in Denmark.
Trial summary
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which cases the death of neurons controlling the voluntary muscles. The death of motor neurons leads eventually to muscle weakness and muscle atrophy and as a consequence thereof, ALS patients die in average within three years after symptom onset due to… Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Cortical Excitability
- What is being tested?
- MRS, conventional TMS and treshold tracking TMS
- How many people
- 0 participants
- Where
- 1 siteDenmark
- Study dates
- 16 Feb 2018to 1 Feb 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients will be recruited among patients examined at the Department of Neurophysiology who are referred for diagnostic neurophysiological examinations without any relation to the proposed project and at the Department of Neurology who are being examining for routine controls. The healthy participants will be recruited by announcement at the homepage www.forsoegsperson.dk/ and by announcement at Aarhus University and Aarhus University Hospital
Who may be able to join
- Patients with
- possible, probable or definite ALS according to international criteria;
- progressive muscular atrophy;
- clinical suspicion of motor neuron disease or ALS
- Healthy participants: no younger than 45 years of age
Who cannot join
- Patients and healthy participants:
- ealier central or peripheral nervous system disease
- pacemaker or other implants
- pregnancy
- use of medications known to affect central nervous system
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Clinical Neurophysiology, Aarhus University Hospital
Aarhus, 8000
About this study
Official title: Assessing Motor Neuron Disease Pathophysiology by Two Novel Methods - Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which cases the death of neurons controlling the voluntary muscles. The death of motor neurons leads eventually to muscle weakness and muscle atrophy and as a consequence thereof, ALS patients die in average within three years after symptom onset due to respiratory failure.
No cure for ALS is currently known, and the medical diagnosis and clinical treatment are impeded by the lack of reliable diagnostic tools for objective disease assessment, and by the limited insight in disease pathophysiology since the underlying disease mechanisms still have not been fully elucidated.
Read more
An unbalance in the concentrations of GABA and glutamate, the most important inhibitory and excitatory brain metabolites, is suggested to play a role in the disease mechanisms of ALS. By applying Magnetic Resonance Spectroscopy (MRS), a magnetic resonance method which allows for quantification of brain metabolites, GABA and glutamate concentration can be quantified and thus hopefully elucidate their role in ALS disease mechanism.
Threshold Tracking Transcranial Magnetic Stimulation (TT-TMS) studies carried out by a single research group have demonstrated cortical hyperexcitability (a physiology state in which neurons in the cerebral cortex are easier activated) as an early feature in ALS patients. For this reason, TT-TMS was suggested as a biomarker of ALS by the research group. However, to be able to suggest a test as a biomarker, one must show the test is reliable and reproducible.
The objectives of this study are therefore: to explore the pathophysiology of ALS by investigating the interaction between neuronal networks as assessed by TT-TMS and conventional TMS and MRS, and to investigate the reliability and reproducibility of TT-TMS. The aim is to examine the utility of TT-TMS and MRS as diagnostic tools for objective detection of ALS in the early disease stage.
The study will include 60 participants in total, subdivided into two groups: 30 healthy participants and 30 patients with clinical suspicion of motor neuron disease or ALS. Each participant will undergo examination with TMS and MRS, the primary outcomes will be compared between the two groups and the results from the TMS examinations and the MRS-scans will be correlated.
- Being tested
- MRS, conventional TMS and treshold tracking TMS
- Keywords
- Treshold Tracking Transcranial Magnetic Stimulation, Magnetic Resonance Spectroscopy, Inter-rater agreement, Reproducibililty of Results, Case-control Studies, Biomarkers, Intra-rater agreement
- 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.
MRS, conventional TMS and treshold tracking TMSDiagnostic test
Using
- two MagStim 200 magnetic stimulator and a figure-of-eightc double 70 mm coil
- SPECIAL MR Spectroscopy sequence
In addition, each group will undergo neurological examination
| Study group | Role | What they receive |
|---|---|---|
| Patients | MRS, conventional TMS and treshold tracking TMS
The participants will be told not to consume coffee or alcohol or do exhausting exercise 12, 24 and 48 hours, respectively, prior to the examinations Receives: Diagnostic Test: MRS, conventional TMS and treshold tracking TMS | |
| Healthy subjects | MRS, conventional TMS and treshold tracking TMS
The participants will be told not to consume coffee or alcohol or do exhausting exercise 12, 24 and 48 hours, respectively, prior to the examinations Receives: Diagnostic Test: MRS, conventional TMS and treshold tracking TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
short interval intracortical inhibition (SICI) measured by threshold tracking TMS
Measurement of the relative change in resting motor threshold during different interstimulus intervals and stimulus intensities
Measured: 8 hours
short interval intracortical inihibition (SICI) measured by conventional TMS
Measurement of the size of motor evoked potentials (MEP) during different interstimulus intervals and a predetermined stimulus intensity
Measured: 8 hours
Concentration of GABA and glutamate
Concentration of GABA and glutamate quantified as a ratio of creatine or tissue water content
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start16 Feb 2018
- Primary completion31 Dec 2023 (estimated)
- Study completion1 Feb 2024 (estimated)
Why it stopped: The part on MRS could not be completed
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.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sándor Beniczky
- Sponsor type
- University, hospital or other
- Collaborators
- Lundbeck Foundation, Aage og Johanne Louis-Hansens Fond, The A.P Moeller Foundation for Advancement of Medical Science, Danish Council for Independent Research, Aarhus University Hospital, Central Denmark Region
- Responsible party
- Sponsor-investigator, Sándor Beniczky, Aarhus University Hospital
- Investigators
- Hatice Tankisi, MD, PhD, Study chair, Department of Clinical Neuropysiology, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03664206
- Sponsor's protocol ID
- AMND
- Other IDs
- 7025-00066B, 18-2B-2454, 17-L-0365, 3530
- Status last verified
- Feb 2024
- First submitted
- 7 Sep 2018
- Last updated
- 2 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Motor Neuron Disease Pathophysiology by Two Novel Methods - Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
- ClinicalTrials.gov ID
- NCT03664206
- Acronym / sponsor ID
- AMND
- Keywords
- Treshold Tracking Transcranial Magnetic Stimulation, Magnetic Resonance Spectroscopy, Inter-rater agreement, Reproducibililty of Results, Case-control Studies, Biomarkers, Intra-rater agreement
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: The part on MRS could not be completed
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sándor BeniczkyUniversity, hospital or other
- Collaborators
- Lundbeck Foundation, Aage og Johanne Louis-Hansens Fond, The A.P Moeller Foundation for Advancement of Medical Science, Danish Council for Independent Research, Aarhus University Hospital, Central Denmark Region
- Study start
- 16 Feb 2018 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 10 Sep 2018 (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.
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which cases the death of neurons controlling the voluntary muscles. The death of motor neurons leads eventually to muscle weakness and muscle atrophy and as a consequence thereof, ALS patients die in average within three years after symptom onset due to respiratory failure.
No cure for ALS is currently known, and the medical diagnosis and clinical treatment are impeded by the lack of reliable diagnostic tools for objective disease assessment, and by the limited insight in disease pathophysiology since the underlying disease mechanisms still have not been fully elucidated.
An unbalance in the concentrations of GABA and glutamate, the most important inhibitory and excitatory brain metabolites, is suggested to play a role in the disease mechanisms of ALS. By applying Magnetic Resonance Spectroscopy (MRS), a magnetic resonance method which allows for quantification of brain metabolites, GABA and glutamate concentration can be quantified and thus hopefully elucidate their role in ALS disease mechanism.
Threshold Tracking Transcranial Magnetic Stimulation (TT-TMS) studies carried out by a single research group have demonstrated cortical hyperexcitability (a physiology state in which neurons in the cerebral cortex are easier activated) as an early feature in ALS patients. For this reason, TT-TMS was suggested as a biomarker of ALS by the research group. However, to be able to suggest a test as a biomarker, one must show the test is reliable and reproducible.
The objectives of this study are therefore: to explore the pathophysiology of ALS by investigating the interaction between neuronal networks as assessed by TT-TMS and conventional TMS and MRS, and to investigate the reliability and reproducibility of TT-TMS. The aim is to examine the utility of TT-TMS and MRS as diagnostic tools for objective detection of ALS in the early disease stage.
The study will include 60 participants in total, subdivided into two groups: 30 healthy participants and 30 patients with clinical suspicion of motor neuron disease or ALS. Each participant will undergo examination with TMS and MRS, the primary outcomes will be compared between the two groups and the results from the TMS examinations and the MRS-scans will be correlated.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Diagnostic Test: MRS, conventional TMS and treshold tracking TMSMRS, conventional TMS and treshold tracking TMS The participants will be told not to consume coffee or alcohol or do exhausting exercise 12, 24 and 48 hours, respectively, prior to the examinations |
| Healthy subjects | – | Diagnostic Test: MRS, conventional TMS and treshold tracking TMSMRS, conventional TMS and treshold tracking TMS The participants will be told not to consume coffee or alcohol or do exhausting exercise 12, 24 and 48 hours, respectively, prior to the examinations |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients will be recruited among patients examined at the Department of Neurophysiology who are referred for diagnostic neurophysiological examinations without any relation to the proposed project and at the Department of Neurology who are being examining for routine controls. The healthy participants will be recruited by announcement at the homepage www.forsoegsperson.dk/ and by announcement at Aarhus University and Aarhus University Hospital
Key inclusion criteria (5 listed)
- Patients with
- possible, probable or definite ALS according to international criteria;
- progressive muscular atrophy;
- clinical suspicion of motor neuron disease or ALS
- Healthy participants: no younger than 45 years of age
Key exclusion criteria (5 listed)
- ealier central or peripheral nervous system disease
- pacemaker or other implants
- pregnancy
- use of medications known to affect central nervous system
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 |
|---|---|---|
| MRS, conventional TMS and treshold tracking TMSUsing * two MagStim 200 magnetic stimulator and a figure-of-eightc double 70 mm coil * SPECIAL MR Spectroscopy sequence In addition, each group will undergo neurological examination | Diagnostic test | Healthy subjects, Patients |
Primary outcome
short interval intracortical inhibition (SICI) measured by threshold tracking TMS
Time frame: 8 hours
Measurement of the relative change in resting motor threshold during different interstimulus intervals and stimulus intensities
short interval intracortical inihibition (SICI) measured by conventional TMS
Time frame: 8 hours
Measurement of the size of motor evoked potentials (MEP) during different interstimulus intervals and a predetermined stimulus intensity
Concentration of GABA and glutamate
Time frame: 1 hour
Concentration of GABA and glutamate quantified as a ratio of creatine or tissue water content
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2024.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Hatice Tankisi, MD, PhD study chair
Department of Clinical Neuropysiology, Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by Sándor Beniczky at 1 site in Denmark.
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 5 inclusion and 5 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: withdrawn, as of the sponsor's last update on 2 Feb 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 Denmark. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
short interval intracortical inhibition (SICI) measured by threshold tracking TMS (time frame: 8 hours). The study lists 3 primary outcomes in all. 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 2 Feb 2024; AzTrials last refreshed its copy on 6 Nov 2026.