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Trial record 1 of 2 for:    19181347 [PUBMED-IDS]
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Transcranial Doppler in Multiple Sclerosis (TRADOMS)

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ClinicalTrials.gov Identifier: NCT02389426
Recruitment Status : Completed
First Posted : March 17, 2015
Last Update Posted : April 17, 2015
Sponsor:
Information provided by (Responsible Party):
Universitair Ziekenhuis Brussel

Brief Summary:
The aim of this study is to investigate the potential of Transcranial doppler (TCD) and Near-Infrared Spectroscopy (NIRS), more simple and non-invasive bedside methods than magnetic resonance imaging (MRI), to evaluate changes in the cerebral circulation between patients with MS and control subjects.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Device: TCD baseline Device: TCD after bosentan administration Device: NIRS baseline Device: NIRS after bosentan administration Not Applicable

Detailed Description:

MS is a poorly understood chronic disease of the central nervous system characterized by focal inflammatory demyelinating lesions and diffuse axonal degeneration. Recent magnetic resonance imaging (MRI) studies demonstrated a widespread decrease in cerebral perfusion - expressed as cerebral blood flow (CBF) - throughout the normal-appearing white matter of patients with MS, which seems not just to be secondary to axonal degeneration with reduced metabolic demands, but in contrast may actively contribute to MS pathology.

Reduced CBF in MS is mediated by elevated levels of the potent vasoconstrictive agent endothelin-1 (ET-1), likely released in the cerebral circulation by reactive astrocytes, and can reversed with administration of the ET-1 antagonist bosentan.

Phase-contrast MRI recently demonstrated reduced cervical arterial blood flow velocities to the brain in patients MS as compared to control subjects. The aim of this study is to investigate the potential of TCD and NIRS, more simple and non-invasive bedside method, to evaluate changes in the cerebral circulation between patients with MS and control subjects.

A baseline TCD examination will be performed in each subject (MS patients and controls) over the temporal bone window on both sides. Middle cerebral artery wave forms will be identified at a depth range of 40-60 mm and a stable forward waveform with good intensity will be selected. TCD probes (2 MHz) will be mounted by a head frame to ensure a constant angle of insonation throughout the procedure. Mean, peak-systolic and end-diastolic blood flow velocities can be directly recorded from the machine. Blood pressure (BP) and heart rate will be measured with a finger plethysmograph. The cuff will be applied to the middle finger of the left hand, first placed at the heart level to calibrate the system, afterwards the hand is placed next to the subject in rest. Near-infrared spectroscopy will be performed to measure cerebral frontal lobe oxygen saturation. NIRS is performed with two large sensors, attached on patient's forehead bilaterally. In bright environments, a light-blocker to cover the sensors will be used to reduce interference from ambient light. Continuously NIRS recording with a 2s interval refreshment. Measurements will be done in upright and supine positions. The expected duration of the entire TCD protocol is 30 minutes.

The TCD examination will be repeated only in the patients with MS (i.e. not in control subjects) 4 h after the oral intake of 62.5 mg bosentan (Tracleer®) (when peak plasma concentrations are expected). This is a purely academic study and Bosentan will be purchased through the hospital pharmacy. The most common side effect of daily treatment with bosentan is hepatotoxicity. Adverse reactions to one single dose are very unlikely. The primary aim is to investigate the potential of TCD to evaluate changes in the cerebral circulation between patients with MS and controls. Bosentan is not the object of investigation in this study but can be considered as a 'Non Investigational Medicinal Product' (N.I.M.P.). Patients with MS will receive the product to increase CBF, an effect which has already been demonstrated in an earlier perfusion-weighted MRI study.

Fifteen patients with relapsing-remitting or progressive MS and 15 healthy controls, matched for sex and age, will be included in this study. Sample size calculation is based on the number of inclusion in previous studies regarding cerebral hemodynamic parameters in MS (mostly between 10 and 30).

The statistical analyses will be conducted with Statistical Package for the Social Sciences (SPSS) software. Mann Whitney U or Wilcoxon signed rank tests will be used where appropriate.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Evaluation of Cerebrovascular Hemodynamics With Transcranial Doppler and Near-infrared Spectroscopy in Patients With Multiple Sclerosis
Study Start Date : December 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan

Arm Intervention/treatment
Experimental: Patients with Multiple Sclerosis
One examination with TCD baseline and with NIRS baseline, and a second examination with TCD after bosentan administration and with NIRS after bosentan administration will be performed; The examination will be repeated only in the patients with MS (i.e. not in control subjects) 4 h after the oral intake of one tablet 62.5 mg bosentan (Tracleer®) (when peak plasma concentrations are expected).
Device: TCD baseline

Measurement of cerebral circulation parameters with transcranial doppler baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Other Name: Transcranial doppler

Device: TCD after bosentan administration

Measurement of cerebral circulation parameters with transcranial doppler after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

Other Names:
  • Transcranial doppler
  • Tracleer
  • Endothelin-1 receptor antagonist

Device: NIRS baseline

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Other Names:
  • Near-infrared spectroscopy
  • ForeSight

Device: NIRS after bosentan administration

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

Other Names:
  • Near-infrared Spectroscopy
  • Endothelin-1 receptor antagonist
  • Tracleer

Experimental: Healthy controls
Only one examination with TCD baseline and NIRS baseline will be performed, without administration of bosentan.
Device: TCD baseline

Measurement of cerebral circulation parameters with transcranial doppler baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Other Name: Transcranial doppler

Device: NIRS baseline

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Other Names:
  • Near-infrared spectroscopy
  • ForeSight




Primary Outcome Measures :
  1. Detection of hemodynamic differences between MS patients and Healthy controls with TCD baseline. [ Time Frame: a 10 minute recording with TCD baseline ]
    Evaluation of cerebral circulation parameters altogether with measured blood pressure and heart rate values.


Secondary Outcome Measures :
  1. Hemodynamic changes in MS patients detected with TCD after administration of Bosentan [ Time Frame: baseline and 4 hours after administration of bosentan a 10 minute recording with TCD ]
    Evaluation of cerebral circulation parameters altogether with measured blood pressure and heart rate values in MS patients, compared before and after administration of bosentan.

  2. Detection of frontal lobe oxygen saturation differences between patients with multiple sclerosis and healthy controls with near-infrared spectroscopy. [ Time Frame: a 10 minute recording with NIRS baseline ]
    Analysis of oxygen saturation measurements of the left and right frontal cerebral lobe.

  3. Frontal lobe oxygen saturation changes in MS patients detected with NIRS after administration of Bosentan [ Time Frame: baseline and 4 hours after administration of bosentan a 10 minute recording with NIRS ]
    Analysis of oxygen saturation measurements of the left and right frontal cerebral lobe in MS patients, compared before and after administration of bosentan.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients with the diagnosis of relapsing-remitting, primary progressive of secondary progressive MS, according to the 2010 revised McDonald criteria.
  • Written informed consent must be obtained.

Exclusion Criteria:

  • MS patients with a known contra-indication for bosentan: liver dysfunction, use of cyclosporine A, allergy.
  • Pregnancy
  • No evidence of MS relapse within the 3 months prior to inclusion.

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): NCT02389426


Locations
Belgium
Department of Neurology, Universitair Ziekenhuis (UZ) Brussel. Center for Neurosciences, Vrije Universiteit Brussel
Jette, Vlaams-Brabant, Belgium, 1090
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Investigators
Principal Investigator: Ilse AS Peeters, Student Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium
Study Chair: Miguel D'haeseleer, MD, PhD Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium
Study Director: Jacques De Keyser, MD, PhD Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

Publications:

Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT02389426     History of Changes
Other Study ID Numbers: B.U.N. 1432101422450
First Posted: March 17, 2015    Key Record Dates
Last Update Posted: April 17, 2015
Last Verified: February 2015

Keywords provided by Universitair Ziekenhuis Brussel:
Multiple Sclerosis
Cerebral hemodynamics
Cerebral hypoperfusion
Cerebral circulation

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Bosentan
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action