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Adrenomedullin for CADASIL (AMCAD)

Primary Purpose

Cadasil

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Adrenomedullin
Sponsored by
National Cerebral and Cardiovascular Center, Japan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cadasil

Eligibility Criteria

20 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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 Patients who cannot perform MRI Patients with active solid malignant tumors Patients who do not give consent to contraception from the date of obtaining consent until the end of the safety evaluation period Pregnant, lactating, and possibly pregnant Patient who participated in another trial within 24 weeks before registration Other patients judged by the Investigator or Investigator to be ineligible for this study

Sites / Locations

  • National Cerebral and Cardiovascular Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adrenomedullin group

Arm Description

Outcomes

Primary Outcome Measures

Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe

Secondary Outcome Measures

Cerebral blood flow change rate evaluated by arterial spin labeling
Frontal lobe
Cerebral blood flow change rate evaluated by arterial spin labeling
Whole brain mean and each area
Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging
Whole brain mean and each area
Change in times of Trail making test-A/B from baseline evaluation
Change in scores of Montreal cognitive assessment from baseline evaluation
Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation
Occurence of cerebral infarction
Cerebral blood flow change rate evaluated by single photon emission computed tomography
Frontal lobe
Safety: Serious adverse event

Full Information

First Posted
October 2, 2023
Last Updated
October 2, 2023
Sponsor
National Cerebral and Cardiovascular Center, Japan
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1. Study Identification

Unique Protocol Identification Number
NCT06072118
Brief Title
Adrenomedullin for CADASIL
Acronym
AMCAD
Official Title
A Multicenter, Single-arm, Clinical Trial of Adrenomedullin for Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 6, 2022 (Actual)
Primary Completion Date
January 23, 2023 (Actual)
Study Completion Date
June 12, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cerebral and Cardiovascular Center, Japan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cadasil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adrenomedullin group
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Adrenomedullin
Intervention Description
Dosing at 15 ng/kg/min for 8 hours is continued for 14 days.
Primary Outcome Measure Information:
Title
Cerebral blood flow change rate evaluated by arterial spin labeling
Description
Frontal lobe
Time Frame
at 28 days post adrenomedullin administration
Secondary Outcome Measure Information:
Title
Cerebral blood flow change rate evaluated by arterial spin labeling
Description
Frontal lobe
Time Frame
at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration
Title
Cerebral blood flow change rate evaluated by arterial spin labeling
Description
Whole brain mean and each area
Time Frame
at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging
Description
Whole brain mean and each area
Time Frame
at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging
Description
Whole brain mean and each area
Time Frame
at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
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
Title
Change in scores of Montreal cognitive assessment from baseline evaluation
Time Frame
at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation
Time Frame
at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
Occurence of cerebral infarction
Time Frame
at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Title
Cerebral blood flow change rate evaluated by single photon emission computed tomography
Description
Frontal lobe
Time Frame
at 28 days post adrenomedullin administration
Title
Safety: Serious adverse event
Time Frame
From the initiation of adrenomedullin administration to 28 days post

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Patients who cannot perform MRI Patients with active solid malignant tumors Patients who do not give consent to contraception from the date of obtaining consent until the end of the safety evaluation period Pregnant, lactating, and possibly pregnant Patient who participated in another trial within 24 weeks before registration Other patients judged by the Investigator or Investigator to be ineligible for this study
Facility Information:
Facility Name
National Cerebral and Cardiovascular Center
City
Suita
State/Province
Osaka
ZIP/Postal Code
564-8565
Country
Japan

12. IPD Sharing Statement

Links:
URL
https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117
Description
Trial registration

Learn more about this trial

Adrenomedullin for CADASIL

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