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

NCT ID: NCT03664206

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-16
• Study Completion Date: 2024-02-01

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Cortical Excitability

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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

MRS, conventional TMS and treshold tracking TMS

Intervention Type: DIAGNOSTIC_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

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

MRS, conventional TMS and treshold tracking TMS

Intervention Type: DIAGNOSTIC_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

Interventions

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Lundbeck Foundation

OTHER

Sponsor Role: collaborator

Aage og Johanne Louis-Hansens Fond

OTHER

Sponsor Role: collaborator

The A.P Moeller Foundation for Advancement of Medical Science

UNKNOWN

Sponsor Role: collaborator

Danish Council for Independent Research

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

Central Denmark Region

OTHER

Sponsor Role: collaborator

Sándor Beniczky

OTHER

Sponsor Role: lead

Responsible Party

Sándor Beniczky

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hatice Tankisi, MD, PhD

Role: STUDY_CHAIR

Department of Clinical Neuropysiology, Aarhus University Hospital

Locations

Department of Clinical Neurophysiology, Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

7025-00066B

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

18-2B-2454

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

17-L-0365

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

3530

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AMND

Identifier Type: -

Identifier Source: org_study_id