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The aim of this pilot study is to assess the efficacy of amiloride in reducing wall enhancement in vertebrobasilar dolichoectasia(VBD) on high-resolution magnetic resonance vessel wall imaging(HR-VWI) via anti-inflammatory mechanisms, clarify the efficacy of amiloride in delaying the progression of VBD, evaluate the safety of amiloride in the treatment of VBD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| amiloride | Experimental | Participants will receive oral amiloride hydrochlorothiazide 1 tablet per day (contains 2.5 mg of amiloride and 25 mg of hydrochlorothiazide per tablet) continuously for 6 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amiloride hydrochlorothiazide | Drug | Amiloride, a potassium-sparing diuretic, also an mTORC2 inhibitor, has been widely utilized in clinical settings. It can be employed as an adjunctive agent for hypertension management and has been investigated in completed clinical trials targeting resistant hypertension. |
| Measure | Description | Time Frame |
|---|---|---|
| Longitudinal changes of CAWE on 5T HR-VWI in VBD following 3 and 6 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular CAWE (3D circumferential arterial wall enhancement: mean signal intensity in T1+Gd images) at 3 and 6 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 3 and 6 months |
| Longitudinal changes of SAWE on 5T HR-VWI VBD following 3 and 6 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular SAWE (specific contrast uptake arterial wall enhancement: the difference in mean signal intensity between T1 and T1+Gd) at 3 and 6 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 3 and 6 months |
| Longitudinal changes of FAWE in VBD on 5T HR-VWI 3 and 6 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular FAWE (focal arterial wall enhancement: areas of the diseased artery with increased AWE) at 3 and 6 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 3 and 6 months |
| Longitudinal changes of WEVR on 5T HR-VWI in VBD following 3 and 6 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular WEVR (3D arterial wall enhancement volume rate) at 3 and 6 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. |
| Measure | Description | Time Frame |
|---|---|---|
| Longitudinal changes of CAWE on 5T HR-VWI in VBD following 12 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular CAWE (3D circumferential arterial wall enhancement: mean signal intensity in T1+Gd images) at 12 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Liuxun Hu | Contact | +8615868058299 | 19111220090@fudan.edu.cn | |
| Wei Zhu | Contact | +8615868058299 | drzhuwei@fudan.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital, Fudan University, Shanghai, Shanghai 200040 | Shanghai | Shanghai Municipality | 200040 | China |
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| ID | Term |
|---|---|
| D014715 | Vertebrobasilar Insufficiency |
| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C010247 | amiloride, hydrochlorothiazide drug combination |
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|
| 3 and 6 months |
| 12 months |
| Longitudinal changes of SAWE on 5T HR-VWI VBD following 12 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular SAWE (specific contrast uptake arterial wall enhancement: the difference in mean signal intensity between T1 and T1+Gd) at 12 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 12 months |
| Longitudinal changes of FAWE on 5T HR-VWI VBD 12 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular FAWE (focal arterial wall enhancement: areas of the diseased artery with increased AWE) at 12 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 12 months |
| Longitudinal changes of WEVR on 5T HR-VWI in VBD following 12 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of vascular WEVR (3D arterial wall enhancement volume rate) at 12 months following initiation of amiloride therapy. The primary objective of this study is to determine whether amiloride exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD. | 12 months |
| Longitudinal changes of vascular dilation on 5T MRA in VBD following 3, 6, and 12 months of amiloride treatment. | Using 5T MRA, we quantify longitudinal changes of dilation(maximum diameter of the intracranial segment of the vertebral artery and basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following amiloride treatment. | 3, 6, and 12 months |
| Longitudinal changes of vascular tortuosity on 5T MRA in VBD following 3, 6, and 12 months of amiloride treatment. | Using 5T MRA, we quantify longitudinal changes of tortuosity(displacement distance of the intracranial segment of the vertebral artery and basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following amiloride treatment. | 3, 6, and 12 months |
| Longitudinal changes of vascular elongation on 5T MRA in VBD following 3, 6, and 12 months of amiloride treatment. | Using 5T MRA, we quantify longitudinal changes of elongation(length of the basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following amiloride treatment | 3, 6, and 12 months |
| Longitudinal changes of thrombus volume in VBD following 3, 6, and 12 months of amiloride treatment. | Using 5T HR-VWI, we quantify longitudinal changes of thrombus volume in VBD at 3, 6, and 12 months following amiloride treatment. | 3, 6, and 12 months |
| Longitudinal changes in plasma SGK1 levels following 1, 3, 6, and 12 months of amiloride treatment in VBD patients. | Longitudinal changes in plasma SGK1 levels (quantitative analysis of plasma SGK1 was performed via western blot) following 1, 3, 6, and 12 months of amiloride treatment in VBD patients. | 1, 3, 6, and 12 months |
| Incidence of ischemic stroke in VBD patients at 3, 6, and 12 months. | Incidence of ischemic stroke(newly developed infarct lesion confirmed by CT/MRI after onset of relevant symptoms/signs or newly developed infarct lesion confirmed by follow-up MRI at 3, 6, or 12 months) in VBD patients at 3, 6, and 12 months. | 3, 6, and 12 months |
| Incidence of subarachnoid hemorrhage associated with VBD rupture in VBD patients at 3, 6, and 12 months. | Incidence of subarachnoid hemorrhage associated with VBD rupture(newly developed subarachnoid hemorrhage confirmed by CT/MRI after onset of relevant symptoms/signs or newly developed subarachnoid hemorrhage confirmed by follow-up MRI at 3, 6, or 12 months) at 3, 6, and 12 months. | 3, 6, and 12 months |
| modified Rankin Scale in VBD patients at 3, 6, and 12 months. | modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability is measured in VBD patients at 3, 6, and 12 months. | 3, 6, and 12 months |
| Five-level EuroQol five-dimensional questionnaire in VBD patients at 3, 6, and 12 months. | Five-level EuroQol five-dimensional questionnaire(EQ-5D-5L), a 5-level, measure of quality of life, is performed in VBD patients at 3, 6, and 12 months. | 3, 6, and 12 months |
| The safety of amiloride in VDB patients | A serious adverse event (SAE) is any untoward medical occurrence that meets one or more of the following criteria, regardless of suspected causal relationship to the study intervention: (1) results in death; (2) is life-threatening; (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability or incapacity, or substantially disrupts normal life functions; or (5) constitutes an important medical event that, based on appropriate medical judgment, may jeopardize the patient's health or require medical or surgical intervention to prevent one or more of the outcomes listed in (1)-(4). SAEs will be actively monitored and systematically assessed at all scheduled follow-up visits (at 1, 3, 6, and 12 months post-baseline). In addition, participants are instructed to report any suspected SAE immediately to the study team via a dedicated 24/7 telephone hotline. To ensure timely detection and documentation. | 1, 3, 6, and 12 months |
| The tolerability of amiloride in VDB patients | Based on prior clinical experience and amiloride trial reports, adverse events (AEs) include dizziness, headache, anorexia, nausea, abdominal distension, fluctuations in blood pressure, and mild electrolyte disturbances (such as hyperkalemia or hypokalemia). In addition, arrhythmias (hyperkalemia-related), allergic reactions (rash, dyspnea), and worsening renal function have been observed. Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety, life-threatening event, or death caused by or associated with amiloride, where the nature, severity, or incidence of such effect, event, or death was not previously identified in the investigational plan; or any other unanticipated serious problem related to amiloride that concerns the rights, safety, or welfare of subjects. | 1, 3, 6, and 12 months |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |