An interventional study of TCD baseline and TCD after bosentan administration in Multiple Sclerosis, sponsored by Universitair Ziekenhuis Brussel. Completed at 1 site in Belgium. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-04-17.
Sponsored by Universitair Ziekenhuis Brussel · Not applicable and Interventional
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.
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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 30 is below the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Universitair Ziekenhuis Brussel is the lead sponsor of 362 studies on the registry; 103 are open to participants now.
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Exclusion Criteria:
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 · Device: TCD after bosentan administration · Device: NIRS baseline · Device: NIRS after bosentan administration
Only one examination with TCD baseline and NIRS baseline will be performed, without administration of bosentan.
Device: TCD baseline · Device: NIRS baseline
Measurement of cerebral circulation parameters with transcranial doppler baseline. This examination will be performed in patients with multiple sclerosis and in healthy controls.
Also known as: Transcranial doppler
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.
Also known as: Transcranial doppler, Tracleer, Endothelin-1 receptor antagonist
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.
Also known as: Near-infrared spectroscopy, ForeSight
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.
Also known as: Near-infrared Spectroscopy, Endothelin-1 receptor antagonist, Tracleer
Detection of hemodynamic differences between MS patients and Healthy controls with TCD baseline.
Evaluation of cerebral circulation parameters altogether with measured blood pressure and heart rate values.
Time frame: a 10 minute recording with TCD baseline
Hemodynamic changes in MS patients detected with TCD after administration of Bosentan
Evaluation of cerebral circulation parameters altogether with measured blood pressure and heart rate values in MS patients, compared before and after administration of bosentan.
Time frame: baseline and 4 hours after administration of bosentan a 10 minute recording with TCD
Detection of frontal lobe oxygen saturation differences between patients with multiple sclerosis and healthy controls with near-infrared spectroscopy.
Analysis of oxygen saturation measurements of the left and right frontal cerebral lobe.
Time frame: a 10 minute recording with NIRS baseline
Frontal lobe oxygen saturation changes in MS patients detected with NIRS after administration of Bosentan
Analysis of oxygen saturation measurements of the left and right frontal cerebral lobe in MS patients, compared before and after administration of bosentan.
Time frame: baseline and 4 hours after administration of bosentan a 10 minute recording with NIRS
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Universitair Ziekenhuis Brussel