Adrenomedullin for CADASIL

NCT06072118 | Completed Phase 2 DMC

• 2 other identifiers: NCVC-AM-CADjRCT2051210117
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cadasil

Outcome Measures

Primary Outcomes (1)

• Cerebral blood flow change rate evaluated by arterial spin labeling

  Frontal lobe

  at 28 days post adrenomedullin administration

Secondary Outcomes (10)

• Cerebral blood flow change rate evaluated by arterial spin labeling

  at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration

• Cerebral blood flow change rate evaluated by arterial spin labeling

  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

  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

  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

  at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration

Study Arms (1)

Adrenomedullin group

EXPERIMENTAL

Drug: Adrenomedullin

Interventions

Adrenomedullin DRUG

Dosing at 15 ng/kg/min for 8 hours is continued for 14 days.

Adrenomedullin group

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have given written informed consent from the patient or the sponsor to participate in the clinical trial
• Patients aged between 20 and 90 at the time of obtaining consent
• Patients diagnosed as CADASIL after confirming NOTCH3 gene mutation by genetic testing
• 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

You may not qualify if:

• Patients who cannot perform cognitive function tests (deafness, blindness, etc., MMSE-J less than 10 points Severe cognitive impairment, etc.)
• Patients received reatment with prohibited drugs or prohibited therapy within the past 12 weeks from the time of registration
• 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
• 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)
• Patients with active infections requiring antibiotic treatment at registration
• Patients with a disability equivalent to modified Rankin Scale 5 at registration
• Patients with severe consciousness impairment (Japan Coma Scale 100 or more)
• Patients with severe renal impairment (estimated GFR less than 30 mL / min / 1.73m2) at registration
• Patients with severe liver damage (transaminase AST (GOT) or ALT (GPT) 100 IU / L or more) at registration
• 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
• Patients with occlusion or severe stenosis of the intracranial main artery or carotid artery at the time of registration
• 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
• Patients with systolic blood pressure less than 100 mmHg at registration
• Patients whose pulse rate is less than 45 beats / minute or 120 beats / minute or more at registration
• Patients with substance abuse or alcoholism

Sponsors & Collaborators

• National Cerebral and Cardiovascular Center, Japan: lead

Study Sites (1)

National Cerebral and Cardiovascular Center

Suita, Osaka, 564-8565, Japan

Location

Related Links

• Trial registration

MeSH Terms

Conditions

CADASIL

Interventions

Adrenomedullin

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neurology, National Cerebral and Cardiovascular Center

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 10, 2023
• Study Start: January 6, 2022
• Primary Completion: January 23, 2023
• Study Completion: June 12, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

JP (1)