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A multicenter, single-arm, clinical trial of adrenomedullin for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Adrenomedullin for CADASIL (AMCAD)

Ihara Masafumi

National Cerebral and Cardiovascular Center

6-1 Kishibe-Shimmachi, Suita, Osaka

ihara@ncvc.go.jp

Imazato Takami

National Cerebral and Cardiovascular Center

6-1 Kishibe-Shimmachi, Suita, Osaka

+81-6-6170-1070

AMCAD@ncvc.go.jp

Not Recruiting

Nov. 01, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

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

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

Both

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarct and Leukoencephalopathy (CADASIL)

Study drug: Adrenomedullin (huAM)
Dosing at 15 ng / kg / min for 8 hours is continued for 14 days.

adrenomedullin, CADASIL, NOTCH3 gene

intravenous, continuous

D046589

D007262

1) Efficacy: Cerebral blood flow change rate evaluated by arterial spin labeling at 28 days post adrenomedullin administration (Frontal lobe)

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)

+81-6-6170-1070

No

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