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

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ClinicalTrials.gov Identifier: NCT03664206
Recruitment Status : Enrolling by invitation
First Posted : September 10, 2018
Last Update Posted : January 14, 2021
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

Tracking Information
First Submitted Date September 7, 2018
First Posted Date September 10, 2018
Last Update Posted Date January 14, 2021
Actual Study Start Date February 16, 2018
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 7, 2018)
  • 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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Assessing Motor Neuron Disease Mechanisms by Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
Official Title Assessing Motor Neuron Disease Pathophysiology by Two Novel Methods - Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy
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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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

Condition
  • Amyotrophic Lateral Sclerosis
  • Motor Neuron Disease
  • Cortical Excitability
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

Study Groups/Cohorts
  • 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

    Intervention: 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

    Intervention: Diagnostic Test: MRS, conventional TMS and treshold tracking TMS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Enrolling by invitation
Estimated Enrollment
 (submitted: September 7, 2018)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Denmark,   Turkey
Removed Location Countries  
 
Administrative Information
NCT Number NCT03664206
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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Sándor Beniczky, Aarhus University Hospital
Study Sponsor Sándor Beniczky
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
Investigators
Study Chair: Hatice Tankisi, MD, PhD Department of Clinical Neuropysiology, Aarhus University Hospital
PRS Account Aarhus University Hospital
Verification Date January 2021