Beta-blockade in Unruptured Intracranial Aneurysm

NCT06249802 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: BBLURAN-CMUJ-14062023
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Intracranial Aneurysm

Keywords

beta-blocker; intracranial aneurysm; rupture prevention; hemodynamic analysis; randomized clinical trial

Outcome Measures

Primary Outcomes (2)

• Intracranial aneurysm growth

  Any increase in size of intracranial aneurysm assessed by radiology specialist based on Magnetic Resonance Angiography.

  12 months

• 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 Outcomes (3)

• All-cause mortality

  12 months

• Change in aneurysmal hemodynamic parameters

  12 months

• Change in aneurysm growth biomarkers

  12 months

Other Outcomes (1)

• 5-year all-cause mortality, intracranial aneurysm rupture or necessity of neurosurgical intervention

  5 years

Study Arms (2)

Nebivolol arm

EXPERIMENTAL

Patients randomly assigned to receive active treatment with escalating doses of nebivolol.

Drug: Nebivolol

Placebo arm

PLACEBO COMPARATOR

Patients randomly assigned to receive matching placebo tablets.

Drug: Placebo

Interventions

Nebivolol DRUG

12-month intake of medication

Nebivolol arm

Placebo DRUG

12-month intake of matching placebo

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jagiellonian University: lead
• University Hospital in Krakow: collaborator

Study Sites (1)

University Hospital in Krakow

Krakow, Lesser Poland Voivodeship, 30-688, Poland

Location

MeSH Terms

Conditions

Intracranial Aneurysm

Interventions

Nebivolol

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aneurysm; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: 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.

Study Record Dates

• First Submitted: January 6, 2024
• First Posted: February 8, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

PL (1)