Adrenomedullin for CADASIL

Cadasil Clinical Trial

— AMCAD  

Official title:

A Multicenter, Single-arm, Clinical Trial of Adrenomedullin for Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06072118
• Other study ID #: NCVC-AM-CAD
• Secondary ID: jRCT2051210117
• Status: Completed
• Phase: Phase 2
• Start date: January 6, 2022
• Est. completion date: June 12, 2023

Study information

• Verified date: October 2023
• Source: National Cerebral and Cardiovascular Center, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 12, 2023
• Est. primary completion date: January 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 90 Years

Eligibility

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:

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

Related Conditions & MeSH terms

• Cadasil
• Dementia, Multi-Infarct

Intervention

Drug:
• Adrenomedullin
Dosing at 15 ng/kg/min for 8 hours is continued for 14 days.

Locations

Country	Name	City	State
Japan	National Cerebral and Cardiovascular Center	Suita	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
National Cerebral and Cardiovascular Center, Japan

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral blood flow change rate evaluated by arterial spin labeling	Frontal lobe	at 28 days post adrenomedullin administration
Secondary	Cerebral blood flow change rate evaluated by arterial spin labeling	Frontal lobe	at 8 hours / 15 days / 90 days / 180 days post adrenomedullin administration
Secondary	Cerebral blood flow change rate evaluated by arterial spin labeling	Whole brain mean and each area	at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Mean diffusivity change rate of the white matter evaluated by MR diffusion tensor imaging	Whole brain mean and each area	at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Fractional anisotropy change rate of the white matter evaluated by MR diffusion tensor imaging	Whole brain mean and each area	at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Change in times of Trail making test-A/B from baseline evaluation		at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Change in scores of Montreal cognitive assessment from baseline evaluation		at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Change in scores of Wechsler Adult Intelligence Scale-Fourth edition from baseline evaluation		at 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Occurence of cerebral infarction		at 8 hours / 15 days / 28 days / 90 days / 180 days post adrenomedullin administration
Secondary	Cerebral blood flow change rate evaluated by single photon emission computed tomography	Frontal lobe	at 28 days post adrenomedullin administration
Secondary	Safety: Serious adverse event		From the initiation of adrenomedullin administration to 28 days post

External Links

•   Trial registration