Assessing Motor Neuron Disease Mechanisms by Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Assessing Motor Neuron Disease Pathophysiology by Two Novel Methods - Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03664206
• Other study ID #: AMND
• Secondary ID: 7025-00066B18-2B
• Status: Withdrawn
• Start date: February 16, 2018
• Est. completion date: February 1, 2024

Study information

• Verified date: February 2024
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Cortical Excitability
• Motor Neuron Disease

Intervention

Diagnostic Test:
• MRS, conventional TMS and treshold tracking TMS
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

Locations

Country	Name	City	State
Denmark	Department of Clinical Neurophysiology, Aarhus University Hospital	Aarhus

Sponsors (7)

Lead Sponsor	Collaborator
Sándor Beniczky	Aage og Johanne Louis-Hansens Fond, Aarhus University Hospital, Central Denmark Region, Danish Council for Independent Research, Lundbeck Foundation, The A.P Moeller Foundation for Advancement of Medical Science

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	8 hours
Primary	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	8 hours
Primary	Concentration of GABA and glutamate	Concentration of GABA and glutamate quantified as a ratio of creatine or tissue water content	1 hour