Beta-blockade in Unruptured Intracranial Aneurysm

Intracranial Aneurysm Clinical Trial

— BBLURAN  

Official title:

Beta-blockade in Unruptured Intracranial Aneurysm

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06249802
• Other study ID #: BBLURAN-CMUJ-14062023
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2025
• Est. completion date: January 1, 2030

Study information

• Verified date: February 2024
• Source: Jagiellonian University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 1, 2030
• Est. primary completion date: January 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-blockers intake
• previous SAH
• intake of ß-blocker currently or in the past
• presence of other intracranial pathology
• history of surgical or endovascular aneurysm treatment
• contraindications for contrast-enhancement MRI examination

Related Conditions & MeSH terms

• Aneurysm
• Intracranial Aneurysm

Intervention

Drug:
• Nebivolol
12-month intake of medication
• Placebo
12-month intake of matching placebo

Locations

Country	Name	City	State
Poland	University Hospital in Krakow	Kraków	Lesser Poland

Sponsors (2)

Lead Sponsor	Collaborator
Jagiellonian University	University Hospital in Krakow

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	5-year all-cause mortality, intracranial aneurysm rupture or necessity of neurosurgical intervention	Yearly follow-up for all-cause mortality or intracranial aneurysm rupture or neurosurgical intervention	5 years
Primary	Intracranial aneurysm growth	Any increase in size of intracranial aneurysm assessed by radiology specialist based on Magnetic Resonance Angiography.	12 months
Primary	Intracranial aneurysm rupture	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).	12 months
Secondary	All-cause mortality	Death of any cause	12 months
Secondary	Change in aneurysmal hemodynamic parameters	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.	12 months
Secondary	Change in aneurysm growth biomarkers	Any change in serum levels of one or more biomarkers: IL-1,IL-6, IL-15, TGF- ß and MCP-1.	12 months