Functional cerebral small vessel studies for HTRA1-related cerebral small vessel disease

JRCT ID: jRCT1030230229

Registered date:14/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: CARASIL, HTRA1-related cerebral small vessel disease
• Date of first enrollment: 14/07/2023
• Target sample size: 25
• Study type: Other

Outcome(s)

• Primary Outcome: A before and after comparison in a single group of patients with HTRA1-related cerebral small vessel disease (including CARASIL) will be performed at 6 months. In other words, the amount of change in cerebral blood flow measured by MRI ASL before and after acetazolamide administration will be defined as cerebral blood flow reactivity under acetazolamide stress. This will be measured twice, once at baseline and again at 6 months, and cerebral blood flow reactivity will be compared at baseline and 6 months.

Secondary Outcome

1. difference in cerebral perfusion reactivity between patients with HTRA1-related cerebral small vessel disease (including CARASIL) and healthy controls
2. change in cerebral perfusion reactivity under acetazolamide load over 6 months in the healthy control group.
3. imaging changes in cognitive function, head and neck vessels, and brain parenchyma at 6 months in patients with HTRA1-related cerebral small vessel disease (including CARASIL).

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old

Include criteria

The patient group is defined as those between 20 and 80 years of age with confirmed HTRA1 mutation or with clinical symptoms and imaging findings consistent with HTRA1-associated cerebral small vessel disease in second-degree relatives of HTRA1 mutation-positive patients.
The healthy group is those who are between 20 and 80 years of age and have not been clinically diagnosed with dementia.

Exclude criteria

1) Patients who have been treated with a prohibited concomitant drug within the last 12 weeks prior to enrollment.
2) Patients who have initiated or changed the dosage of a prohibited concomitant medication within the past 4 weeks prior to enrollment.
3) Patients with active infections requiring systemic treatment
4) Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2)
5) Patients with severe hepatic impairment (AST (GOT) or ALT (GPT) > 100 U/L)
6) Patients with abnormal serum sodium or potassium levels requiring therapeutic correction.
7) Patients with a 12-lead ECG showing QT prolongation or shortening requiring therapeutic correction.
8) Patients with a history of cerebral infarction, intracranial hemorrhage, transient ischemic attack, or cerebral aneurysm with a high probability of rupture diagnosed within the last 12 weeks prior to enrollment.
9) Patients being treated for or with a history of coronary artery disease (angina, myocardial infarction).
10) Patients with poorly controlled respiratory disease (asthma, chronic obstructive pulmonary disease, etc.)
11) Patients with occlusion or significant stenosis of the main intracranial artery or carotid artery
12) Patients with systolic blood pressure below 100 mmHg
13) Patients with pulse rate less than 45 beats/minute or greater than 120 beats/minute
14) Patients with drug abuse or alcoholism
15) Patients unable to obtain an adequate head MR scan
16) Patients with active malignant neoplastic disease
17) Patients who are pregnant, lactating, or who may become pregnant between the date of informed consent and the date of study completion.
18) Patients who have participated in other studies involving the administration of investigational products within 24 weeks prior to enrollment.
19) Other patients deemed ineligible for the study by the investigator or others.

Related Information

• Primary Sponsor: Onodera Osamu
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development