Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarct and Leukoencephalopathy (CADASIL) adrenomedullin, CADASIL, NOTCH3 gene
Conditions
Interventions
Study drug: Adrenomedullin (huAM)
Dosing at 15 ng / kg / min for 8 hours is continued for 14 days.
Sponsors
Ihara Masafumi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients who have given written informed consent from the patient or the sponsor to participate in the clinical trial 2) Patients aged between 20 and 90 at the time of obtaining consent 3) Patients diagnosed as CADASIL after confirming NOTCH3 gene mutation by genetic testing 4) Patients with Mini-mental state examination-J score of 10-27 or Trail maiking test score (age ajustment) of average + 1.5 SD (standard deviation) or higher
Exclusion criteria
Exclusion criteria: 1) Patients who cannot perform cognitive function tests (deafness, blindness, etc., MMSE-J less than 10 points Severe cognitive impairment, etc.) 2) Patients received reatment with prohibited drugs or prohibited therapy within the past 12 weeks from the time of registration 3) Patients who started to take concomitant restriction drugs or changed dosage of concomitant restriction drugs within the past 4 weeks from the time of registration 4) Patients whose Mini-mental state examination-J with 4 or more points improvements between the time of registration and 4 weeks or more at the time of screening (If patients who take concomitant restriction drugs) 5) Patients with active infections requiring antibiotic treatment at registration 6) Patients with a disability equivalent to modified Rankin Scale 5 at registration 7) Patients with severe consciousness impairment (Japan Coma Scale 100 or more) 8) Patients with severe renal impairment (estimated GFR less than 30 mL / min / 1.73m2) at registration 9) Patients with severe liver damage (transaminase AST (GOT) or ALT (GPT) 100 IU / L or more) at registration 10) Patients diagnosed as having cerebral infarction or intracranial hemorrhage or transient ischemic attack or cerebral aneurysm with high probability of rupture within the last 12 weeks from the time of registration 11) Patients with occlusion or severe stenosis of the intracranial main artery or carotid artery at the time of registration 12) Patients with significant ECG abnormalities (atrioventricular block of 2-3 degrees, extension of QRS interval of 120 ms or more, extension of QTcB of 450 msec or more) at registration, or past histroy of acute coronary syndrome or acute heart failure within the last 12 weeks from the time of registration 13) Patients with systolic blood pressure less than 100 mmHg at registration 14) Patients whose pulse rate is less than 45 beats / minute or 120 beats / minute or more at registration 15) Patients with substance abuse or alcoholism 16) Patients who cannot perform MRI 17) Patients with active solid malignant tumors 18) Patients who do not give consent to contraception from the date of obtaining consent until the end of the safety evaluation period 19) Pregnant, lactating, and possibly pregnant 20) Patient who participated in another trial within 24 weeks before registration 21) Other patients judged by the Investigator or Investigator to be ineligible for this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1) Efficacy: Cerebral blood flow change rate evaluated by arterial spin labeling at 28 days post adrenomedullin administration (Frontal lobe) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Safety: Serious adverse event 2) Efficacy: Cerebral blood flow change rate evaluated by arterial spin labeling at 8 hours/15 days/90 days/180 days post adrenomedullin administration (Frontal lobe) 3) Efficacy: Cerebral blood flow change rate evaluated by arterial spin labeling at 8 hours/15 days/28 days/90 days/180 days post adrenomedullin administration (Whole brain mean and each area) 4) Efficacy: Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging at 8 hours/15 days/28 days/90 days/180 days post adrenomedullin administration (Whole brain mean and each area) 5) Efficacy: Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging at 8 hours/15 days/28 days/90 days/180 days post adrenomedullin administration (Whole brain mean and each area) 6) Efficacy: Trail making test change (TMT)-A and B score change at 15 days/28 days/90 daysv180 days post adrenomedullin administration 7) Efficacy: Montreal cognitive assessment (MoCA) score change at 15 days/28 days/90 days/180 days post adrenomedullin administration 8) Efficacy: Wechsler Adult Intelligence Scale-Fourth edition (WAIS-IV) score change at 15 days/28 days/90 days/180 days post adrenomedullin administration 9) Efficacy: Occurence of cerebral infarction at 8 hours/15 days/90 days/180 days post adrenomedullin administration 10) Efficacy: Cerebral blood flow change rate evaluated by Single photon emission computed tomography (SPECT) at 28 days post adrenomedullin administration (Frontal lobe) | — |
Contacts
Public ContactTakami Imazato
National Cerebral and Cardiovascular Center
Outcome results
None listed