Clinical trial NCT04613427: Predictors of Rupture Risk of Intracranial Aneurysms
Official title: Predictors of Rupture Risk of Intracranial Aneurysms - Impact of Lipid Metabolism and Mitochondrial Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Intracranial Aneurysm
Lead sponsor: University of Bergen
Sponsor class: OTHER
First posted: 2020-11-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to Haukeland University Hospital with either aneurysmal subarachnoid hemorrhage or unruptured intracranial aneurysm.

Brief summary: Patients admitted to Haukeland University Hospital with either UIA or aSAH underwent a measurement of bioelectrical impedance and body mass composition using InBody 10. Lipids and lipoproteins were collected from plasma. 60 patients in total were included in the study.

Detailed description: Subarachnoid hemorrhage (SAH) is a condition mainly caused by the rupture of intracranial aneurysms. The estimated prevalence of intracranial aneurysms in the general population is 1-2%, with an annual incidence of aneurysm rupture causing subarachnoid hemorrhage estimated around 1% in Norway. The mortality rates for aneurysmal subarachnoid hemorrhage (aSAH) are as high as 35%, and for the survivors the condition represents a significant morbidity with long-term cognitive impairment and other challenges. With a mean age of 51-55 years at presentation, the burden, both for the patients themselves and on health care resources, is substantial.

Thus, the risk assessment and management of patients with unruptured intracranial aneurysms (UIA) represents a substantial challenge. The number of patients with incidentally discovered cerebral aneurysms is rapidly growing with the increasing use of non-invasive intracranial magnetic resonance imaging (MRI). Therapy options are endovascular coiling, neurosurgical clipping, or observation. To decide whether to perform a potentially harmful prophylactic procedure or not, better tools to predict the risk of rupture in the given individual are required.

Some risk factors, both for the development of an intracranial aneurysm and for the rupture leading to hemorrhage are identified, such as hypertension, age and smoking. Recent research has shown that obesity and hypercholesterolemia is surprisingly associated with an apparent lower risk of aSAH. However, underlying body composition and dyslipidemic patterns has not yet been explored. Increased knowledge of predictors for aneurysm rupture is required, both to improve the patient care and the decision-making concerning the neurosurgical prevention of aSAH.

In the RAPID project, the investigators aim to identify potential new risk factors for the rupture of intracranial aneurysms by comparing the lipid and lipoprotein profile and the body mass composition in patients with UIA and aSAH.

Direct-segmental multisegmental bioimpedance analysis (DSM-BIA) is a valid tool for the assessment of total body and segmental composition and has shown excellent agreements when compared with dual energy X-ray absorptiometry (DEXA). Body composition will be analysed within day 2 after intervention or surgery using a DSM-BIA scanner (InBody S10, BioSpace Ltd, Seoul, South Korea).

Lipids will be measured enzymatically in ethylenediaminetetraacetic acid (EDTA) plasma/serum on a Hitachi 917 system (Roche Diagnostics GmbH, Mannheim, Germany) using the triacylglycerol (GPO-PAP), cholesterol (CHOD-PAP), HDL-cholesterol plus and LDL-cholesterol plus kit from Roche Diagnostics, and the non-esterifies fatty acid (NEFA FD) kit and the phospholipids kit (Phospholipids FS) from "DiaSys Diagnostic Systems GmbH" (Holzheim, Germany). Glucose will be measured in EDTA-plasma using the Gluco-quant Glucose/HK (GLU) kit from Roche. The total fatty acid composition in EDTA-plasma will be analysed using gas chromatography/mass spectrometry (GC/MS).

Lipoprotein particle size analysis will be performed by proton nuclear magnetic resonance (NMR) spectroscopy. Particle concentrations of lipoproteins of different sizes will be calculated from the measured amplitudes of their spectroscopically lipid methyl group NMR signals. Lipoprotein particle size will be derived from the sum of diameter of each subclass multiplied by its relative mass percentage based on the amplitude of its methyl NMR signal. Particle size analysis will be performed by the Norwegian University of Science and Technology (NTNU).

Eligibility criteria: Inclusion Criteria:

* Admitted electively for treatment of unruptured intracranial aneurysm
* Admitted acutely for aneurysmal subarachnoid hemorrhage
* Informed consent form signed by patient or close relative

Exclusion Criteria:

* Pregnant
* Pacemaker
* Subarachnoid hemorrhage without identified aneurysmal rupture
* Unruptured aneurysm with previous SAH/intracranial hemorrhage

Primary outcomes:
measure: Anthropometric risk factors of ruptured versus unruptured intracranial aneurysms
timeFrame: The anthropometric data will be collected within 96 hours after admittance, as well as information on the predictors and risk factors from the patient journal.
Secondary outcomes:
measure: Standard lipid risk factors of ruptured versus unruptured intracranial aneurysms
timeFrame: Blood samples collection within 96 hours after admittance. Calculations will be performed within 3 years after study completion (June 2022).
measure: Lipid ratios as risk factors of ruptured versus unruptured intracranial aneurysms
timeFrame: The calculations will be performed prior to statistical analyses within 3 years after study completion (June 2022).
measure: Apolipoprotein risk factors of ruptured versus unruptured intracranial aneurysms
timeFrame: Blood samples collection within 96 hours after admittance.
measure: Apolipoprotein A1/B ratio as a risk factor of ruptured versus unruptured intracranial aneurysms
timeFrame: Calculations will be performed within 3 years after study completion (June 2022).
measure: Lipoprotein subclass risk factors of ruptured versus unruptured intracranial aneurysms.
timeFrame: Blood samples collection within 96 hours after admittance.
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: University of Bergen
state: Hordaland
Study officials:
affiliation: Haukeland University Hospital
name: Christian A Helland, MD PhD
role: STUDY_DIRECTOR
References: