Beta-blockade in Unruptured Intracranial Aneurysm
- Registration Number
- NCT06249802
- Lead Sponsor
- Jagiellonian University
- Brief Summary
Subarachnoid haemorrhage is a devastating type of stroke, with high mortality and morbidity rate. In approximately 85% of cases, it is caused by an intracranial aneurysm rupture. Majority of patients with diagnosed intracranial aneurysm are eligible for interventional treatment, however, some patients are managed conservatively. Currently, the only recommendations for patients with conservatively managed intracranial aneurysms, are routine imaging follow-ups and minimization of rupture risk factors. There are no medications proven to decrease risk of aneurysm rupture, that might be prescribed to such patients. In preliminary study the investigators found that patients with intracranial aneurysms who took β-blockers had significantly smaller aneurysm rupture rate and dome size, as well as more favorable hemodynamic parameters. No other antihypertensive drugs showed similar associations. Therefore, in this project the investigators aim to further analyze the impact of β-blocker intake on fate of intracranial aneurysm and find possible explanations for its protective role. The investigators aim to perform a randomised, double-blind, placebo-controlled clinical trial. One hundred patients with unruptured intracranial aneurysm, , qualified to conservative management will be enrolled. Two arms (50 patients each) will be receiving nebivolol or matching placebo. Treatment in each arm will last 12 months. The following examinations will be performed at baseline and at 6 and 12 months: clinical assessment, angio-MRI with vessel wall imaging, Doppler ultrasound to extract blood flow waveforms from Internal Carotid Artery, Vertebral Artery Middle Cerebral Artery, Anterior Cerebral Artery and Posterior Cerebral Artery, as well as blood samples. Based on the results the investigators will assess changes in aneurysm size and wall contrast enhancement. The investigators will also analyze levels of possible aneurysm growth biomarkers in peripheral blood. Additionally, the investigators will prepare three-dimensional models of the artery harbouring aneurysm and perform patient-specific computer modelling of blood flow through such artery to assess hemodynamic parameters of aneurysm dome. All obtained measurements will be compared at baseline and at 6 and 12 months. The investigators hypothesize that, in comparison to the placebo group, β-blocker therapy in patients with unruptured intracranial aneurysm will contribute to favorable changes in hemodynamic parameters of aneurysm dome, decrease wall degradation process and prevent from aneurysm growth.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 100
- freshly (within 12 months) diagnosed unruptured intracranial aneurysm, non-eligible for surgical or endovascular treatment
- age > 18 years
- informed consent
- contraindications to β-blockers intake
- previous SAH
- intake of β-blocker currently or in the past
- presence of other intracranial pathology
- history of surgical or endovascular aneurysm treatment
- contraindications for contrast-enhancement MRI examination
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo arm Placebo Patients randomly assigned to receive matching placebo tablets. Nebivolol arm Nebivolol Patients randomly assigned to receive active treatment with escalating doses of nebivolol.
- Primary Outcome Measures
Name Time Method Intracranial aneurysm growth 12 months Any increase in size of intracranial aneurysm assessed by radiology specialist based on Magnetic Resonance Angiography.
Intracranial aneurysm rupture 12 months Fatal or non-fatal intracranial aneurysm rupture. Outcome will be determined based on presence of subarachnoid hemorrhage on head Computer Tomography (performed in case on any symptoms).
- Secondary Outcome Measures
Name Time Method All-cause mortality 12 months Death of any cause
Change in aneurysmal hemodynamic parameters 12 months 5% increase or decrease (relative to measurement at baseline) of one or more following parameters:
* dome fraction very high Oscillatory Shear Index (defined as percentage of aneurysm dome with Oscillatory Shear Index higher than 0.2)
* dome fraction of very low Wall Shear Stress (defined as percentage of aneurysm dome with Wall Shear Stress lower than 0.5)
* Surface Vortex Fraction (defined as as percentage of flow with positive Q-criterion in small layer near aneurysm wall) All parameters will be determined based on computer modelling of blood flow in aneurysm dome.Change in aneurysm growth biomarkers 12 months Any change in serum levels of one or more biomarkers: IL-1,IL-6, IL-15, TGF- β and MCP-1.
Trial Locations
- Locations (1)
University Hospital in Krakow
🇵🇱Kraków, Lesser Poland, Poland