Role of cerebral hypoperfusion in multiple sclerosis (ROCHIMS)

Autor: Ayla Pauwels, Hubert Raeymaekers, Veronique Michiels, Stéphanie Hostenbach, Miguel D'haeseleer, Anne-Marie Van Binst, Jacques De Keyser, Annick Van Merhaeghen-Wieleman, Peter Van Schuerbeek
Přispěvatelé: Neuroprotection & Neuromodulation, Faculty of Medicine and Pharmacy, Clinical sciences, Neurology, Radiology, Brain, Body and Cognition, Psychiatry, Medical Imaging
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Endothelin Receptor Antagonists
Time Factors
N-acetyl aspartate
Ultrasonography
Doppler
Transcranial
ENERGY-METABOLISM
Medicine (miscellaneous)
Axonal degeneration
Research & Experimental Medicine
FATIGUE
Bosentan/adverse effects
law.invention
Multiple Sclerosis
Relapsing-Remitting/diagnostic imaging
Study Protocol
0302 clinical medicine
Randomized controlled trial
Belgium
law
Centrum semiovale
magnetic resonance imaging
Pharmacology (medical)
030212 general & internal medicine
Cognitive decline
Depression (differential diagnoses)
SCALE
Randomized Controlled Trials as Topic
Cerebrovascular Circulation/drug effects
lcsh:R5-920
Cerebral blood flow
IMPAIRMENT
medicine.anatomical_structure
Treatment Outcome
Medicine
Research & Experimental
Cerebrovascular Circulation
Cardiology
lcsh:Medicine (General)
Life Sciences & Biomedicine
medicine.drug
APPEARING WHITE-MATTER
medicine.medical_specialty
Endothelin Receptor Antagonists/adverse effects
Proof of Concept Study
White matter
Multiple sclerosis
03 medical and health sciences
Multiple Sclerosis
Relapsing-Remitting
Double-Blind Method
Internal medicine
medicine
Humans
INTERNATIONAL COGNITIVE ASSESSMENT
Science & Technology
business.industry
Bosentan
medicine.disease
business
030217 neurology & neurosurgery
Zdroj: Trials, Vol 20, Iss 1, Pp 1-7 (2019)
TRIALS, 20:164. BMC
Trials
ISSN: 1745-6215
DOI: 10.1186/s13063-019-3252-4
Popis: Background Axonal degeneration is related to long-term disability in patients with multiple sclerosis (MS). The underlying mechanism remains ill understood but appears to involve axonal energetic dysfunction. A globally impaired cerebral blood flow (CBF) has been observed in the normal-appearing white matter (NAWM) of patients with MS, which is probably related to astrocytic overexpression of endothelin-1 (ET-1). Cerebral hypoperfusion has been associated with reduced mitochondrial activity and disabling symptoms (e.g. fatigue and cognitive decline) of MS. Countering this process could therefore be beneficial in the disease course. Short-term CBF restoration with a single 62.5-mg dose of the ET-1 receptor antagonist bosentan has already been demonstrated in patients with MS. Methods The ROCHIMS study is a proof-of-concept double-blind randomized clinical trial in which patients with relapsing-remitting MS will receive either 62.5 mg bosentan or matching placebo twice daily during 28 ± 2 days. Clinical evaluation and brain magnetic resonance imaging (MRI) will be performed at baseline and treatment termination. Based on previous work, we expect a global increase of CBF in the individuals treated with bosentan. The primary outcome measure is the change of N-acetyl aspartate in centrum semiovale NAWM, which is a marker of regional axonal mitochondrial activity. Other parameters of interest include changes in fatigue, cognition, motor function, depression, and brain volume. Discussion We hypothesize that restoring cerebral hypoperfusion in MS patients improves axonal metabolism. Early positive effects on fatigue and cognitive dysfunction related to MS might additionally be detected. There is a medical need for drugs that can slow down the progressive axonal degeneration in MS, making this an important topic of interest. Trial registration Clinical Trials Register, EudraCT 2017-001253-13. Registered on 15 February 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3252-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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