Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease, with no proven disease-modifying treatments. Adrenomedullin, a vasoactive peptide, has angiogenic, vasodilation, anti-inflammatory, and anti-oxidative properties and could have triple sites of action on components of the neuro-glial-vascular unit consisting of vessels, microglia and oligodendrocytes or, more specifically, on the white matter oligovascular unit. The aim of the AMCAD trial is to assess the safety and efficacy of Adrenomedullin in CADASIL patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Dosing at 15 ng/kg/min for 8 hours is continued for 14 days.
National Cerebral and Cardiovascular Center
Suita, Osaka, Japan
Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe
Time frame: at 28 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe
Time frame: at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by arterial spin labeling
Whole brain mean and each area
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in times of Trail making test-A/B from baseline evaluation
Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Montreal cognitive assessment from baseline evaluation
Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation
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Time frame: at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Occurence of cerebral infarction
Time frame: at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Cerebral blood flow change rate evaluated by single photon emission computed tomography
Frontal lobe
Time frame: at 28 days post adrenomedullin administration
Safety: Serious adverse event
Time frame: From the initiation of adrenomedullin administration to 28 days post