Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03664206
Recruitment Status : Enrolling by invitation
First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
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
Information provided by (Responsible Party):
Sándor Beniczky, Aarhus University Hospital

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.


Condition or disease Intervention/treatment
Amyotrophic Lateral Sclerosis Motor Neuron Disease Cortical Excitability Diagnostic Test: MRS, conventional TMS and treshold tracking TMS

Layout table for study information
Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Assessing Motor Neuron Disease Pathophysiology by Two Novel Methods - Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
Actual Study Start Date : February 16, 2018
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : August 31, 2019


Group/Cohort Intervention/treatment
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

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


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

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





Primary Outcome Measures :
  1. 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

  2. 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

  3. Concentration of GABA and glutamate [ Time Frame: 1 hour ]
    Concentration of GABA and glutamate quantified as a ratio of creatine or tissue water content



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664206


Locations
Layout table for location information
Denmark
Department of Clinical Neurophysiology, Aarhus University Hospital
Aarhus, Denmark, 8000
Turkey
Department of Neurology, Gazi University Hospital
Ankara, Turkey
Sponsors and Collaborators
Sándor Beniczky
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
Investigators
Layout table for investigator information
Study Chair: Hatice Tankisi, MD, PhD Department of Clinical Neuropysiology, Aarhus University Hospital

Layout table for additonal information
Responsible Party: Sándor Beniczky, Professor, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT03664206     History of Changes
Other Study ID Numbers: AMND
7025-00066B ( Other Grant/Funding Number: Independent Research Fund Denmark )
18-2B-2454 ( Other Grant/Funding Number: Aage og Johanne Louis-Hansens Fond )
17-L-0365 ( Other Grant/Funding Number: The A.P. Møller Foundation )
3530 ( Other Grant/Funding Number: Lundbeck Foundation )
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sándor Beniczky, Aarhus University Hospital:
Treshold Tracking Transcranial Magnetic Stimulation
Magnetic Resonance Spectroscopy
Inter-rater agreement
Reproducibililty of Results
Case-control Studies
Biomarkers
Intra-rater agreement

Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases