Clinical trial NCT06249802: Beta-blockade in Unruptured Intracranial Aneurysm
Official title: Beta-blockade in Unruptured Intracranial Aneurysm
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Intracranial Aneurysm
Keywords: beta-blocker
intracranial aneurysm
rupture prevention
hemodynamic analysis
randomized clinical trial
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
Collaborators: name: University Hospital in Krakow
First posted: 2024-02-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patient recruitment into study will be continuous during first three years of project duration. Two arms will be created - receiving nebivolol or placebo. Dosage of nebivolol will be determined based on blood pressure and heart rate. The investigators aim to enroll a total of 100 patients - 50 for β-blocker treatment arm and 50 for placebo arm. At baseline, included patients will undergo detailed clinical examination, MRI to assess aneurysm morphology and wall, as well as vascular Doppler ultrasound to provide boundary condition for computer modelling. During first 6 months of trial, monthly control visits for each patient will be established, during which they will undergo physical examination. After 6 and 12 months all examinations will be repeated. Further follow-up will then be adopted.
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* freshly (within 12 months) diagnosed unruptured intracranial aneurysm, non-eligible for surgical or endovascular treatment
* age \> 18 years
* informed consent

Exclusion Criteria:

* 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

Primary outcomes:
measure: Intracranial aneurysm growth
timeFrame: 12 months
measure: Intracranial aneurysm rupture
timeFrame: 12 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: 12 months
measure: Change in aneurysmal hemodynamic parameters
timeFrame: 12 months
measure: Change in aneurysm growth biomarkers
timeFrame: 12 months
Other outcomes:
measure: 5-year all-cause mortality, intracranial aneurysm rupture or necessity of neurosurgical intervention
timeFrame: 5 years
Locations:
city: Kraków
country: Poland
facility: University Hospital in Krakow
state: Lesser Poland
Study officials:
References: