SuSPect-CAA: Superficial Siderosis in Patients With Suspected Cerebral Amyloid Angiopathy

Sponsor

Ludwig-Maximilians - University of Munich (Other)

Overall Status

Unknown status

CT.gov ID

NCT01856699

Collaborator

(none)

302

Enrollment

Location

Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aim of the SuSPect-CAA study is to prospectively evaluate the prognostic significance of cortical superficial siderosis in patients with suspected cerebral amyloid angiopathy with a primary focus on future stroke and mortality.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage Cerebral Amyloid Angiopathy Ischemic Stroke

Detailed Description

Non-traumatic cortical superficial siderosis (cSS) is a common finding in patients with cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. The clinical features and course as well as the prognostic significance of cSS in CAA patients remain unclear. In a retrospective study we have previously shown that cSS might be an important predictor or warning sign for future intracranial hemorrhage. However, prospective data are missing.

The Superficial Siderosis in Patients with suspected Cerebral Amyloid Angiopathy (SuSPect-CAA) study is designed as a prospective observational multi-centre cohort study. Primary objective of the study is to evaluate if cSS is a predictor for future stroke and mortality (primary endpoint: combined rate of stroke and death after 36 months). Secondary objectives of the study include 1) to evaluate if cSS represents a marker of future intracranial haemorrhage, especially at the site of initial siderosis, 2) to describe the clinical presentation and course of cSS, 3) to assess to associated imaging findings, 4) to determine the differential diagnoses of cSS.

All subjects presenting to the respective neurological centers (out- or inpatient treatment with neuroimaging) will be screened. The study population will consist of two patient groups:

Patients meeting the modified Boston criteria for probable or possible CAA, i. e. patients with SS +/- lobar intracerebral hemorrhage or microbleeds in cortico-subcortical localization and absence of other cause of hemorrhage than CAA will be assigned to the study group. 2) Patients meeting the classic Boston criteria for possible or probable CAA but without any SS will be assigned to the control group. A total of 100 patients per group will be enrolled. Baseline and follow-up assessment at 6, 12, 24, and 36 months will be performed by visits in the respective neurological outpatient clinic including a structured interview and neurological exam, neuropsychological tests, EEG and MRI.

Study Design

Study Type:

Observational

Actual Enrollment :

302 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Observational Study on the Prognostic Relevance of Supratentorial Superficial Siderosis in Patients With Suspected Cerebral Amyloid Angiopathy

Study Start Date :

May 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Study Group Patients with cortical superficial siderosis and possible or probable cerebral amyloid angiopathy meeting the modified Boston criteria.
Control Group Patients with possible or probable cerebral amyloid angiopathy meeting the classic Boston criteria but without any cortical superficial siderosis.

Outcome Measures

Primary Outcome Measures

Combined rate of stroke and death [36 months]
All cause mortality and stroke (WHO-definition)

Secondary Outcome Measures

Rate of intracranial hemorrhage [6, 12, 24, 36 months]
Rate of any intracranial hemorrhage as assessed by cerebral imaging

Other Outcome Measures

Clinical presentation and course of superficial siderosis [0, 6, 12, 24, 36 months]
A detailed analysis on the clinical presentation and course of superficial siderosis will be performed (detailed questionnaire, comprehensive neurological examinations, disability scales, neuropsychological tests)
Imaging findings associated with superficial siderosis [0, 6, 12, 24, 36 months]
Localization, extent and progression of superficial siderosis will be assessed on MR-imaging. In addition, the prevalence, incidence, localization, number or extent of cerebral microbleeds, white matter disease, and acute ischemic lesions will be determined using follow-up MRI.
Differential causes of superficial siderosis [0, 6, 12, 24, 36 months]
At the time of patient screening and follow-up we will systematically evaluate the underlying causes of superficial siderosis and potential differential diagnoses based on the available clinical, laboratory and imaging data, as well as published diagnostic criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (study group):

Fulfillment of the modified Boston criteria for CAA-related hemorrhage with evidence of supratentorial superficial siderosis on MRI
MR-/CT-/digital subtraction (DS) -angiography without evidence of cerebral aneurysm, arterio-venous malformation (AVM) , AV-fistula or other pathology of relevance (e.g. tumor, hemorrhagic infarction)
A maximum of two lobar or cerebellar intracranial hemorrhages (ICH) (old or acute)
Written informed consent by patient or guardian prior to study participation
Willingness to participate in follow-up

Inclusion Criteria (control group):

Fulfillment of the classic Boston criteria for CAA-related hemorrhage
Absence of superficial siderosis on MRI
A maximum of two lobar or cerebellar ICHs (old or acute)
MR-/CT-/DS -angiography without evidence of cerebral aneurysm, AVM, AV-fistula or other pathology of relevance (e.g. tumor, hemorrhagic infarction)
Written informed consent by patient or guardian prior to study participation
Willingness to participate in follow-up

Exclusion Criteria (both groups):

Severe medical condition with expected life expectancy <3 years
More than two lobar or cerebellar ICH (old or acute)
any intracerebral hemorrhage in the deep grey matter (basal ganglia or thalami) or in the brain stem
History of head trauma resulting in loss of consciousness or radiologically visible traumatic brain injury (contusions, diffuse axonal damage) in the last 5 years prior to inclusion
Cerebral aneurysm or history of aneurysmal subarachnoid hemorrhage
Infratentorial siderosis
Infratentorial subarachnoid hemorrhage

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ludwig-Maximilians-University	Munich		Germany	81377

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

Investigators

Principal Investigator: Frank Wollenweber, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilans-University
Principal Investigator: Jennifer Linn, MD, Department of Neuroradiology, Carl Carus University Dresden
Principal Investigator: Christian Opherk, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilans-University
Study Director: Martin Dichgans, MD, Institute for Stroke and Dementia Research, Ludwig-Maximilians-University