Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06128824
Other study ID # HIFI-CAA-01
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date March 19, 2019
Est. completion date March 31, 2026

Study information

Verified date November 2023
Source Ludwig-Maximilians - University of Munich
Contact Martin Dichgans, MD
Phone +49 89 4400
Email martin.dichgans@med.uni-muenchen.de
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Cerebral amyloid angiopathy (CAA), caused by amyloid beta depositions in the walls of small cerebral vessels, is remarkably common in the elderly. Its major clinical consequences include intracerebral hemorrhages (ICH) typically in lobar location, functional dependence (disability) and cognitive impairment. Cortical superficial siderosis (cSS) is a common finding in CAA patients and can even be the only magnetic resonance imaging sign of CAA. cSS is of high prognostic relevance regarding future intracerebral haemorrhage and disability. Previous studies suggest that cSS is caused by recurrent focal subarachnoid hemorrhages (fSAH). However, the exact mechanisms and the temporal dynamics of this highly relevant imaging finding are largely unknown. In addition to hemorrhagic manifestations, such as cSS, CAA patients also show ischemic lesions. Of particular interest are acute ischemic lesions as detected by diffusion imaging, which seem to be highly prevalent. Since haemorrhagic and ischemic lesions require fundamentally different therapeutic strategies, understanding the relevance and interplay of both lesion types is highly important for clinical decision making. The HIFI-CAA cohort study aims to provide novel insights into cSS, acute ischemic lesions and other relevant brain alterations in CAA through high-frequency (monthly) serial magnetic resonance imaging.


Description:

Cerebral amyloid angiopathy (CAA) is defined as the deposition of β-amyloid in the walls of small cortical cerebral vessels. It is very common in the elderly population with prevalence rates up to 60% and is associated with Alzheimer´s disease. Intracerebral lobar macrohemorrhages (ICH) are the most devastating presentation of CAA and the main cause of morbidity and mortality. In addition to developing clinically manifest strokes, CAA patients may also suffer from transient neurological symptoms and progressive cognitive impairment ultimately resulting in dementia. Apart from ICH, typical MRI signs of CAA include multiple cerebral microbleeds (CMB) in a cortical-subcortical localization, white matter hyperintensities on T2-weighted images and supratentorial cortical superficial siderosis (cSS). Main risk factors for recurrence of CAA-related ICH are apolipoprotein E ε2 or ε4 alleles, previous ICHs and CMB on follow-up imaging. Recently, cSS emerged as an additional, major independent risk factor for ICH and disability. In CAA, siderosis affects the convexity of the cerebral hemispheres, and thus is termed cortical superficial siderosis (cSS). This is in contrast to infratentorial superficial siderosis, which is not linked to CAA. CSS is likely caused by recurrent non-traumatic, focal convexity subarachnoid hemorrhages (fSAH). There are causes of fSAH and cSS other than CAA, and these causes seem to vary depending on age: in younger patients (< 60 years of age) fSAH and cSS are most commonly seen in the context of trauma, vasculitis and reversible cerebral vasoconstriction syndrome, while CAA seems to be the by far most common cause in subjects above 60 years of age. cSS is common (> 60%) in patients with histologically proven CAA, and may be the only hemorrhagic imaging sign on MRI. Lesions on diffusion-weighted imaging, i.e. areas of restricted diffusion, are a very frequent finding in CAA. These diffusion restrictions can be found in 25% to 50% of CAA patients when performing a single MRI. One recent study even suggests a spatial relationship with cSS. The clinical significance of these lesions is not yet fully established. The most likely pathophysiology behind these lesions is acute ischemia, or to be more precise cytotoxic edema after brain ischemia/infarction. However, subcortical infarcts as detected through a diffusion-restricted lesion can have vastly different fates, ranging from disappearance to complete brain tissue loss (cavitation). An important step in the understanding of these lesions is the precise estimation of prevalence and tissue consequences. A critical point in this endeavour is that these diffusion restricted lesions are typically only visible for a few weeks. Thus, they can remain completely undetected in studies using conventional study designs with follow-up intervals as long as 6 months, one year or even longer. While small subcortical and cortical ischemic lesions (detectable as diffusion restrictions) are a common finding in CAA patients, their exact prevalence and relevance for disease progression are unclear. Overall, temporal dynamics of the processes leading to hemorrhagic and ischemic manifestations of CAA as well as their interrelationships are insufficiently understood. These critical aspects can be addressed by a novel study design with serial, monthly magnetic resonance imaging. The study design is inspired by a recent high-frequency serial imaging study in patients with sporadic, non-amyloid cerebral small vessel disease conducted at Nijmegen (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort - Investigating The origin and Evolution of cerebral small vessel disease, RUN DMC - InTENse). The primary aim of this study is to prospectively evaluate the development and temporal evolution of incident and prevalent fSAH & cSS in CAA patients. Secondary aims are i) to assess the monthly incidence of acute ischemic lesions (diffusion restrictions) in CAA patients with cSS/fSAH and to compare the incidence with lobar ICH survivors, and ii) to assess the inter-relationship between hemorrhagic lesions (fSAH/cSS/CMB) and acute ischemic lesions as well as the association between these lesions and cerebrovascular event rates and functional status.


Recruitment information / eligibility

Status Recruiting
Enrollment 75
Est. completion date March 31, 2026
Est. primary completion date March 31, 2025
Accepts healthy volunteers No
Gender All
Age group 50 Years and older
Eligibility Inclusion Criteria: - Probable CAA according to the modified Boston criteria with evidence of 1. cSS or fSAH 2. lobar ICH survivors without cSS or fSAH - Absence of ICH or microbleed in deep locations (basal ganglia, thalamus, brain stem) - Absence of infratentorial siderosis or infratentorial SAH - MR-/CT-/DS-angiography without evidence of cerebral aneurysm, AVM, AV-fistula or other possible etiology for the observed haemorrhagic manifestations - No history of head trauma resulting in loss of consciousness or radiologically visible traumatic brain injury - Written informed consent by patient herself/himself prior to study enrolment Exclusion Criteria: - Unwillingness to participate in high-frequency (monthly) follow-up - Severe medical condition with expected life expectancy <1 year - Contraindications for MRI (following local guidelines of the respective study center)

Study Design


Related Conditions & MeSH terms


Intervention

Other:
MR Imaging
Serial magnetic resonance imaging (MRI)

Locations

Country Name City State
Germany DZNE/Bonn - Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn Bonn
Germany DZNE/Magdeburg - Universitätsklinikum Magdeburg Magdeburg
Germany Insitute for Stroke and Dementia Research Munich

Sponsors (1)

Lead Sponsor Collaborator
Martin Dichgans

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary new hemorrhagic features as determined by heme-sensitive MRI new hemorrhagic features (e.g., cSS) as determined by heme-sensitive magnetic resonance imaging such as T2*-weighted gradient echo (GRE) and susceptibility weighted imaging (SWI) monthly up to 12 months
Secondary DWI+ lesions on diffusion weighted imaging MRI DWI+ lesions on diffusion weighted imaging (DWI) on magnetic resonance imaging monthly up to 12 months
Secondary modified Rankin Scale functional outcome on modified Rankin Scale (score [0-6] with higher scores meaning a worse outcome) monthly up to 12 months
Secondary neuropsychological evaluation (global cognition using MoCA) neuropsychological evaluation of cognition using the Montreal Cognitive Assessment (MoCA) (score [0-30] with higher scores meaning a better outcome) baseline and after 12 months
Secondary neuropsychological evaluation (global cognition using MMSE) neuropsychological evaluation of cognition using the Mini Mental State Examination (MMSE) (score [0-30] with higher scores meaning a better outcome) baseline and after 12 months
Secondary neuropsychological evaluation (processing speed and executive function) neuropsychological evaluation of processing speed and executive function using the Trail Making Test (TMT) A and TMT B measuring the time in seconds to complete the task; age- and education-corrected z-scores will be derived baseline and after 12 months
Secondary reaction time (attention) reaction time assessed with Test of Attentional Performance (TAP) test monthly up to 12 months
See also
  Status Clinical Trial Phase
Completed NCT05486897 - Periventricular White Matter Hyperintensities in Cerebral Amyloid Angiopathy and Hypertensive Arteriopathy
Recruiting NCT03969732 - Multimodal Biomarkers for Diagnosis and Prognosis in CAA Phase 3
Completed NCT03542656 - Application of Amyloid PET in Cerebral Amyloid Angiopathy Phase 3
Recruiting NCT04604587 - MRI-visible Enlarged Perivascular Spaces and the Alteration of Lymphatic Drainage System in CAA Phase 3
Completed NCT05565144 - Brain Hemorrhage and Functional Outcome in Stroke Patients With CAA Features on Pre-thrombolysis MRI Treated With Intravenous Thrombolysis (Thrombolysis in CAA) ( Thromb in CAA )
Active, not recruiting NCT03464344 - Cortical Superficial Siderosis and Risk of Recurrent Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy. N/A
Completed NCT03824197 - Auburn University Research on Olive Oil for Alzheimer's Disease (AU-ROOAD) N/A
Recruiting NCT06393712 - A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy Phase 2
Active, not recruiting NCT01856699 - Superficial Siderosis in Patients With Suspected Cerebral Amyloid Angiopathy N/A
Completed NCT01821118 - Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy Phase 2
Not yet recruiting NCT06421532 - Stimulating Amyloid Clearance in Cerebral Amyloid Angiopathy Phase 2
Completed NCT05394636 - Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy
Recruiting NCT04204642 - SEarchiNg biomarkErs Cerebral Amyloid Angiopathy (SENECA)
Recruiting NCT05207475 - Safety and Efficacy of Remote Ischemic Conditioning on Cerebral Amyloid Angiopathy. (RIC-CAA) N/A
Recruiting NCT04757597 - Remote Ischemic Conditioning for Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage N/A
Not yet recruiting NCT02361411 - Methods of Etiological Diagnosis of Cerebral Amyloid Angiopathy N/A
Not yet recruiting NCT04654026 - the Safety and Efficacy of Antiplatelet Therapy in Patients of CAA
Completed NCT05082194 - Balance Eyesight and Muscle Tension in the Cervical Spine in Cerebral Amyloid Angiopathy
Completed NCT04825808 - Detailed Clinical and MRI Characteristics in Primary Non-traumatic Convexity Subarachnoid Haemorrhage Elderly Patients.
Recruiting NCT05680389 - Antibiotics Against Amyloid Angiopathy Phase 1/Phase 2