Effects of Amlodipine and other blood pressure lowering agents on microvascular function in Small Vessel Diseases
- Conditions
- Cerebral small vessel diseaseTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2016-002920-10-DE
- Lead Sponsor
- Klinikum der Universitaet Muenchen AoeR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 105
•Symptomatic SVD defined as
oHistory of clinical lacunar stroke in the last 5 years with a corresponding recent small subcortical infarct visible on MRI scan or CT scan compatible with the clinical syndrome. On MRI, recent infarct is defined as a DWI lesion on the acute MRI scan. On CT, recent infarct is defined as a novel infarct on CT within 3 weeks after the event that was not visible on the admission CT. Patients admitted to the hospital with an obvious lacunar syndrome and an admission CT/CT perfusion compatible with a lacunar infarct but without an MRI in the (sub)acute stage and no repeat CT performed in the context of clinical care can be recruited for TREAT-SVDs. After providing informed consent they will be invited for the screening visit including a 3T MRI. The 3T MRI will be used to verify the presence of a new lesion, relative to the admission CT, compatible with a lacunar infarct and compatible with the lacunar syndrome. If such a lesion is present the patient will undergo the further TREAT-SVDs workup. If no such lesion is observed the patient will be excluded from the study and considered as a screening failure.
oor cognitive impairment defined as visiting a memory clinic with cognitive complaints, objective cognitive impairment * and capacity to consent, and with confluent deep white matter hyperintensities (WMH) on MRI (defined on the Fazekas scale as deep WMH score = 2) (*concluded by the treating physician based on a validated cognitive measurement tool (for example but not limited to MoCA or CAMCOG))
oor a diagnosis of CADASIL established by molecular genetic testing of the NOTCH3 gene (presence of an archetypical, cysteine-affecting mutation) or the presence of granular osmiophilic material in ultrastructural, electron microscopy analysis of skin biopsy
•Indication for antihypertensive treatment (as defined by meeting one of the following):
oHypertension defined as systolic blood pressure (SBP) =140mmHg or diastolic BP (DBP) =90mmHg without antihypertensive treatment or use of an antihypertensive drug for previously diagnosed hypertension
oPrior history of stroke or transient ischaemic attack (TIA)
•Age 18 years or older
•Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
•Unwillingness or inability to give written consent
•Pregnant or breastfeeding women, women of childbearing age not taking contraception.
Acceptable contraception in women of childbearing age is a highly effective” contraceptive measure as defined by the Clinical Trials Facilitation Group
•Contraindications to MRI (pacemaker, aneurysm clip, cochlear implant etc.)
•Other major neurological or psychiatric conditions affecting the brain and interfering with the trial design (e.g. multiple sclerosis)
•In case of clinical lacunar stroke syndrome other causes of stroke such as
o=50% luminal stenosis (NASCET) in large arteries supplying the area of ischaemia
omajor-risk cardioembolic source of embolism (permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) myocardial infarction, left ventricular ejection fraction less than 30%, valvular vegetations, or infective endocarditis)
oother specific causes of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse)
•Other stroke risk factor requiring immediate intervention that would preclude involvement in the trial
•Renal impairment (eGFR <35ml/min)
•Life expectancy <2 years
•Use of >2 antihypertensive drugs at maximum dose or equivalent (one drug at the maximum dose and two drugs at half of the maximum dose) for an appropriate BP control
•Contraindications to the applied antihypertensive drug
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The calcium channel blocker amlodipine has a superior beneficial effect on cerebrovascular reactivity in patients with symptomatic SVDs when compared to either the Angiotensin II type 1 (AT1) receptor blocker losartan or the beta-blocker atenolol.;Secondary Objective: Losartan has a superior beneficial effect on cerebrovascular reactivity when compared to atenolol.;Primary end point(s): Cerebrovascular reactivity (CVR) as determined by BOLD MRI (T2*) brain scan response to hypercapnic challenge.;Timepoint(s) of evaluation of this end point: end of the 2 week run-in phase and after 4 weeks of monotherapy.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Mean SBP assessed by daily telemetric monitoring within the last week of the run-in phase and within the last week of each treatment phase<br>•Blood pressure variability (BPv) operationalized as coefficient of variation (100*standard deviation (std)/mean SBP) across multiple measurements and assessed by daily telemetric monitoring within the last week of the run-in phase and within the last week of each treatment phase<br>;Timepoint(s) of evaluation of this end point: see E.5.2