Clinical Research Directory

Florida Cerebrovascular Disease Biorepository and Genomics Center

The purpose of this study is to create a state-wide biorepository and resource center for cerebrovascular diseases in Florida, which will include collecting medical history information and blood from subjects affected by cerebrovascular disease. The information and blood samples collected may be used in future research for the study of cerebrovascular disease and to learn about, prevent or treat other health problems.

Follow-up Extension Study of Regular Physical Exercise in Patients With Symptomatic Intracranial Arterial Stenosis

This study will include the subjects with symptomatic intracranial arterial stenosis (ICAS) who have participated in and completed the 1-year follow-up of RESIST trial (NCT06615726). The aim is to observe the long-term clinical outcomes over 3 years after a 1-year regular physical exercise intervention in patients with symptomatic ICAS.

Diagnosis of Transient Ischemic Attacks in the Emergency Department

Patients presenting a Transient Ischemic Attack (TIA) and admitted to the Emergency Department should be referred to a neurovascular specialist. In recent years, several hospitals have established TIA clinics. These units are day hospitals where all the necessary examinations are performed. Access to this expertise has proven beneficial in reducing cardiovascular morbidity and mortality, particularly the risk of early recurrence. Unfortunately, this access is limited by issues of medical demographics and unequal access to the healthcare system. In practice, this ideal care is not always possible. A portion of the TIA population is at low risk, and diagnostic and therapeutic interventions are limited, not always requiring neurovascular expertise. The hypothesis of this research is that the management of a patient who has suffered a TIA (additional examinations, treatment, referral) is not linked to their cardiovascular risk and that the performance of additional examinations and therapies is incomplete.

Regular Physical Exercise in Patients With Symptomatic Intracranial Arterial Stenosis

The objective of this study is to evaluate the effectiveness and safety of regular physical exercise in preventing ischemic stroke events in patients with symptomatic intracranial arterial stenosis.

Symptomatic Carotid Outcomes Registry

The purpose of this study is to build upon trials done over 30 years ago, which did not include statins, new antiplatelet agents, and newer antihypertensive medications. Since the landmark trials (NASCET, ECST), there have been new developments in medical stroke prevention, which creates a gap in knowledge. The aim of this study is to evaluate that clinical care with Intensive Medical Therapy (IMT) alone, the one year stroke rate in patients with symptomatic carotid stenosis and low risk clinical features will be \<5%.

Radiofrequency and Cryoablation of the Posterior Wall of the Left Atrium

Atrial fibrillation (AF) is the cause of 20% of strokes, and the risk of stroke in a person suffering from this arrhythmia increases by 5 times. Ischemic stroke in patients with AF is often fatal and, compared with stroke of other etiology, leads to the most pronounced disability and more often recurs. Accordingly, the risk of death in patients with AF-related stroke is 2 times higher, and treatment costs increase 1.5 times. The main interventional method of treating AF, available in most medical institutions, is the use of radio frequency and/or cryoenergy to eliminate destructive damage to the left atrium (LA). The aim of this study is to compare two different interventional methods and identify predictors of recurrence in patients with persistent and long-term AF.

Stroke School -Including Physical Exercise, Patient Education and Individual Follow-up Sessions

In a randomized controlled trial the effect of 12 weeks of cross-sectorial physical exercise combined with patient education and individual follow-up session is investigated in patients with minor stroke or non-disabling stroke.

Ticagrelor Based De-Escalation of Dual Antiplatelet Therapy in Ischemic Stroke

This is a randomized, controlled, outcome assessor blind, parallel group design pilot study on 100 patient with diagnosis of ischemic stroke admitted in Bou-Ali Sina Hospital, Sari,Iran.The aim of study is to compare the efficacy of 90 mg ticagrelor BID plus aspirin for 1 month and 60 mg ticagrelor BID plus aspirin for 6 months in reduce of non-disabling non-cardioembolic ischemic stroke or high risk TIA recurrence during first 12 months.

Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke

This prospective non-interventional cohort study investigates the pathophysiology of Atrial Fibrillation Detected After Stroke or transient ischemic attack (AFDAS) by comparing the autonomic function and inflammation between patients with AFDAS, patients with atrial fibrillation (AF) diagnosed before the ischemic event or known AF (KAF), and patients with normal sinus rhythm (NSR) after 14 day of cardiac monitoring following the event onset.

Empowerment and Mobile Technology in the Control of Cardiovascular Risk Factors in Patients With Ischemic Stroke

The CARDIOSTROKE is a randomized trial comparing mobile-device assisted control of hypertension together with screening of occult atrial fibrillation to standard care in patients with recent ischemic stroke or transient ischemic attack.

Imaging and Serological Biomarkers of Autonomic Dysfunction After Ischemic Stroke

The goal of this observational study is to * to investigate the prevalence and time course of autonomic dysfunction in acute ischemic stroke patients; * to evaluate the influence of lesion location on autonomic dysfunction; * to identify patterns of structural and functional brain connectivity within the central autonomic control circuits associated with autonomic dysfunction; and * to explore causal models of the link between brain lesions; cardiac, immunological and endocrine biomarkers; and dysautonomia. Researchers will compare patients with acute ischemic stroke to patients with transient ischemic attacks to study the effect of acute ischemic brain lesions. Participants will * undergo cardiovascular autonomic function testing; * receive structural and functional MR imaging; * provide blood samples for determinaton of serological biomarkers auf dysautonomia.

Stroke-Card Registry

Stroke is the second leading cause of death and one of the main contributors to disability. Patients who survive the acute phase of ischemic stroke and those with transient ischemic attack (TIA) are at high risk of subsequent vascular events. Importantly, recurrent strokes are associated with a higher social and economic impact, higher case fatality, and worse clinical outcome than first-ever strokes. The burden of post-stroke complications, residual deficits, and inadequate medical and psychosocial care all contribute to long-term disability and reduced quality of life in these patients. The Department of Neurology of the Medical University Innsbruck undertook the STROKE-CARD trial (NCT02156778) between 2014 and 2018 with follow-up until 2019 to evaluate the efficacy of the Post-Stroke disease-management program STROKE-CARD care. After implementation of STROKE-CARD care, the investigators aim to document the quality of post-stroke care and compare outcome parameters to historical cohorts and the change over time. Furthermore the investigators aim to gain a large data-resource for future research of biomarkers, disease mechanisms, prognosis and imaging mechanisms for R\&D.

StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Randomized Controlled Trial

Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST - RCT, the investigators will assess the impact of starting versus not starting a statin in frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA) on their health-related quality of life and Major Adverse Cardiovascular Events (MACE) free survival during a two-year follow-up period.

Smartwatches for Detection of Atrial Fibrillation (AFib) in Secondary Prevention of Cryptogenic Stroke

Scientific Background: In secondary prevention of ischemic stroke, detection of atrial fibrillation (AFib) and subsequent anticoagulation therapy reduce the risk of recurrent stroke by approximately 60%. Prolonged electrocardiogram (ECG) monitoring up to 6 months significantly increases detection of AFib in cryptogenic stroke. Wearables like smartwatches have recently been shown to adequately detect AFib in the general population. Thus, prolonged ECG monitoring after cryptogenic ischemic stroke or transient ischemic attack (TIA) using a smartwatch could lead to a reduction of recurrent stroke by prompting adequate anticoagulation therapy and may constitute a cost-effective, non-invasive, and broadly-available alternative to the current standard of care. Hypothesis: The investigators hypothesize that AFib detection via smartwatch in patients with cryptogenic TIA or ischemic stroke is accurate compared to an implantable event recorder. Methods: The investigators introduce a prospective, intraindividual-controlled, multicentre clinical study in patients with cryptogenic ischemic stroke or TIA. In addition to an implanted event recorder as indicated by clinical standard, included patients receive a smartwatch for detection of AFib. ECG-data from smartwatches will be continuously monitored by two independent cardiologists. As soon as AFib is confirmed, a doctoral appointment is set to evaluate start of anticoagulation. The follow-up period will be six months. The study consists of four study visits: a baseline visit, two phone visits at one and three months, and an end of trial visit at six months. Primary Objective: To compare smartwatch and event recorder based analysis for sensitivity and specificity of AFib detection per patient after six months

Genotype Guided Antiplatelet Therapy in Ischemic Stroke

A fifth of ischemic stroke or transient ischemic attack (TIA) patients will have recurrent events within the first 3 months \[Refs 1-3\] despite aggressive medical therapy with antiplatelets and risk factor control. Clopidogrel is one of the mainstays of antiplatelet secondary prevention therapy in patients with ischemic stroke. CYP2C19 loss of function (LOF) mutations impair the effectiveness of clopidogrel \[Ref 4\]. The prevalence of LOF mutations is approximately 60% in the local population \[Ref 5\], rendering the effectiveness of empiric clopidogrel treatment doubtful. For patients who have LOF mutations, other treatment options for secondary prevention of ischemic stroke need to be tested. This study aims to determine the feasibility and clinical impact of genetic testing guided antiplatelet therapy in ischemic stroke patients on the prevention of major adverse cardiovascular or cerebrovascular events. Clopidogrel naive ischemic stroke or TIA patients aged 21 years and above will be randomised to genetic testing guided antiplatelet therapy or standard medical therapy within 7 days of their index event. Patients allocated to testing group will have blood sample drawn for diagnosis of CYP2C19 LOF mutations. Patients who test positive for an LOF mutation (intermediate and poor metabolisers) will be offered alternative antiplatelet therapy in the form of aspirn (for those who need monotherapy) or aspirin plus ticagrelor or dipyridamole (for those who need dual antiplatelet therapy) to be decided by the managing physician. Patients who test negative for LOF mutation will continue on clopidogrel. Platelet reactivity index (enables the identification of patients with an inadequate response to antiplatelet agents) will be measured at baseline.

Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE

Antiphospholipid syndrome (APS) has a close association with ischemic stroke; however, the optimal treatment strategy for APS-related stroke has yet to be established. The clinical guidelines suggest using warfarin for APS-related stroke, but these suggestions are largely based on retrospective studies from the 1990s and expert opinion, rather than high-quality clinical trials. Moreover, the evidence on the role of antiplatelet drugs other than aspirin (e.g., clopidogrel) in APS-related stroke is particularly limited. Considering the relatively young age of patients with APS and the high clinical burden of using warfarin, it is necessary to verify whether warfarin is essential. Thus, the investigators aim to compare clopidogrel-based antiplatelet therapy and warfarin as a secondary preventive medication for patients with APS-related stroke. APS-STROKE is an exploratory, multicenter, prospective, randomized, open, blinded-endpoint clinical trial. Adult patients with definite APS who have a history of ischemic stroke will be included. Patients with high-risk APS (triple positivity or persistently high titers of anti-cardiolipin or anti-β2-glycoprotein I antibodies), systemic lupus erythematous, or indications for continued antiplatelet or anticoagulant therapy will be excluded. Eligible patients will be 1:1 randomized to receive clopidogrel-based antiplatelet therapy or warfarin. Patients assigned to the clopidogrel-based antiplatelet therapy group will be permitted to use additional antiplatelet drugs other than clopidogrel at the investigator's discretion. The primary outcome is a composite of any death, major adverse cardiovascular events, systemic thromboembolic events, and major bleeding during a follow-up period of at least 4 years. This study would provide valuable information for determining the optimal secondary prevention strategy for APS-related stroke.

Extracellular Vesicles and Dysregulated Coagulation in the Prediction of Stroke

Annually 100,000 strokes occur, placing stroke as the largest cause of disability in the UK. 90% of strokes are preventable, leading to national focus on programmes including "The National Stroke Programme" to act on preventing, treating, and improving post-stroke care. Importantly, over 25% of ischaemic stroke sufferers have previously had a Transient Ischaemic Attack (TIA), which presents the biggest concern for TIA patients. There are no measures which reliably identify TIA patients most likely to suffer a stroke. Novel biomarkers for predicting stroke are key to addressing this problem. The PREDICT-EV study aims to screen 300 TIA patients and follow them over 12-months. The investigators will determine if a novel biomarker we've identified to increase thrombotic risk (endothelial derived extracellular vesicles) and the resulting increased prothrombin time is associated with patients at highest risk of stroke.

TIA Scores' Mortality Predictions and Recurrent TIA and Stroke Prediction

Our study adopts a prospective design. Our research aims to determine the significance of ABCD2, ABCD3-I, Canadian TIA Score, and NIHSS Score in predicting the likelihood of ischemic stroke within 30 days in patients presenting to the emergency department with transient ischemic attack (TIA)

European Blood Pressure Intensive Control After Stroke

Stroke is the third most common cause of death worldwide and the leading cause of disability. High blood pressure is an important risk factor for stroke. Lowering a person's blood pressure reduces the risk of future stroke or heart attack, and current guidelines recommend treatment to a target of \<130mmHg for secondary prevention. Home blood pressure measurement and telemonitoring are acceptable to patients, but there is uncertainty over the use of out of office blood pressure measurements in stroke patients in guidelines. This is a study designed to establish the feasibility of a larger clinical trial, comparing home blood pressure monitoring, telemonitoring and medication titration with standard care. The study hypothesis is that home BP measurement and telemonitoring with medication titration may lead to improved BP control compared to standard of care clinical practice.

Mobility Assessment in Multi-morbidity

Multimorbidity (the presence of two or more coexisting long-term conditions) is a significant challenge facing the NHS, especially given UK's ageing population and the association with high levels of illness burden and healthcare costs. Over 50% of adults \>65 years have multiple long-term conditions (MLTCs). Our group has validated a broad range of algorithms applied to single wearable sensors that have the potential to capture walking-related mobility outcomes (such as walking cadence and walking speed) accurately and reliably during activities of daily living across five single long-term conditions. These algorithms, however, cannot be readily applied to people with MLTCs because the effect of multimorbidity on mobility is amplified compared to single long-term conditions secondary to a greater number of complications and sequelae. Accordingly, the aim of this study is to validate algorithms that would allow robust estimation of walking-related mobility outcomes during daily life activities in MLTCs. To meet our objectives, the investigators will perform: i) laboratory-based technical validation of existing and newly developed algorithms for walking-related mobility outcome detection; ii) unsupervised real-life validation of selected algorithms; and iii) examination of how well the validated walking-related mobility outcomes reflect global and disease specific characteristics in older adults with multimorbidity. The investigators will adopt an integrated patient-centric approach where patients with MLTCs will be engaged early in the project to provide input of their perception and concerns regarding mobility limitation in daily life activities. The investigators aim to recruit 55 older adults (\>65 years), men and women, with multiple long-term conditions with the following inclusion criteria: having two or more of the following conditions including osteoarthritis, rheumatoid arthritis, osteoporosis, type 2 diabetes, depression and/or anxiety, hypertension, coronary heart disease, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, asthma, bronchiectasis, chronic kidney disease, cancer, or stroke within the last 5 years.

Cerebrovascular Disease: Quality of Life (CODE: QoL)

The goal of this observational study is to learn about quality of life, stress and caregiver burden in patients with stroke and their caregivers. The main question is: • to discover the factors associated with quality of life and stress in patient-caregiver dyads. Participants will be asked to fill out questionnaires and agree to provide a hair sample (in order to measure stress hormones in hair) and consent to use of their routine clinical and laboratory data. Researchers will compare a group of participants without stroke to establish a comparable baseline.

Florbetaben for Imaging of Vascular Amyloid

The Primary Objective is to determine if a new nuclear tracer (named 18F-Florbetaben) used with nuclear imaging (PET imaging) can detect inflamed plaque in patients with recent ACS or stroke/TIA.

Life After Transient Ischemic Attack

Background: Transient ischemic attack (TIA) is defined as acute neurological symptoms of vascular origin, which resolves completely within 24 hours. However, emerging evidence indicates that up to 1/3 of patients is experiencing (non-focal) lasting symptoms, such as fatigue, depression, and anxiety. Aim: The aim of this study is to investigate self-reported lasting symptoms after TIA, timing of these symptoms as well as their potential resolution and characterize patients who have high risk for developing these symptoms. Method: This is a prospective cohort study which will include 350-400 patients with TIA from a single comprehensive stroke care center which serves the population in North Denmark Region, one of five administrative regions in Denmark (Stroke Unit, Aalborg University Hospital). Outcome measures include patient-reported outcomes collected at discharge, 3, 6 and 12 months and semi-structured interviews with a selected sample of patients. Perspective: This study will provide much needed insights into the development of lasting symptoms in patients with TIA in a cohort with presumed high external validity. Based on these results, a person-centered intervention will be designed to support the return to everyday life for patients with TIA.

Angiogenic Markers in Cerebrovascular Disease (ANFIS)

Intracranial atherosclerosis (ICAS) is the most common cause of stroke worldwide. It carries a worse prognosis than other stroke etiologies, with an annual rate of recurrent stroke and death of 15% despite intensive medical management, and as high as 35% in certain populations. Overall, treatment and prevention of stroke due to ICAS has been unsuccessful. While two recent clinical trials have shown modest improvement in the efficacy of intensive medical treatment, these trials were terminated early given the elevated rate of complications, stroke, and death in the interventional arms. In fact, intensive medical management appears to reduce the risk of embolism; however, medical management alone does not address the progression of intracranial arterial stenosis or the pathophysiologic components of hypoperfusion and poor collateral circulation. Levels and types of various angiogenic factors in the blood and tissues have been proposed to be predictive of patient outcome after ischemic stroke and treatment for stroke. This study therefore pursues a new paradigm to investigate responses to ICAS treatment from the perspective of cerebral collateral vessel generation and the role of angiogenic factors. Specifically, pro- and anti-angiogenic factors in patients with ICAS are evaluated at baseline and longitudinally in response to both medical and surgical treatment. For this we have developed methodologies for the isolation and measurement of these growth factors in plasma of patients with ICAS. These methodologies will enable us to obtain a detailed understanding of the variation and dynamic properties of local and circulating angiogenic factors over time in response to medical and surgical treatment, and their association to outcome phenotypes. This analysis is complemented by studies of angiographic development of neovascularization. If successful, this study will help to better understand the role of angiogenesis in ICAS and create a foundation from which to explore therapeutic treatments for ICAS which harness the natural processes of angiogenesis.