EffecTs of Amlodipine and other Blood PREssure Lowering Agents on responsiveness of small brain blood vessels in chronic vascular brain disease.

Phase 1

• Conditions: Cerebral small vessel disease; MedDRA version: 20.0Level: LLTClassification code 10051765Term: LeukoaraiosisSystem Organ Class: 100000004852; MedDRA version: 20.1Level: LLTClassification code 10070557Term: White matter hyperintensitiesSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-002920-10-GB
• Lead Sponsor: Klinikum der Universitaet Muenchen AoeR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-15
• Last Update Posted: 21 May 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Patients may be enrolled in the trial if all of the following criteria have been met:

- Symptomatic SVD defined as
o History 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.
o or cognitive impairment defined as visiting a memory clinic with cognitive complaints, and a clinical dementia rating (CDR) score of =0.5, and capacity to consent, and with confluent deep white matter hyperintensities (WMH) on MRI (defined on the Fazekas scale as deep WMH score = 2)
o or 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):
o Hypertension defined as SBP =140mmHg or diastolic BP (DBP) =90mmHg without antihypertensive treatment or use of an antihypertensive drug for previously diagnosed hypertension
o Prior 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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Patients will be excluded from the trial for any of the following reasons:
o Inclusion criteria are not met
o Unwillingness or inability to give written consent
o 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
(http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion
o Contraindications to MRI (pacemaker, aneurysm clip, cochlear implant etc.)
o Other major neurological or psychiatric conditions affecting the brain and interfering with the trial design (e.g. multiple sclerosis)
o In case of clinical lacunar stroke syndrome other causes of stroke such as
- =50% luminal stenosis (NASCET) in large arteries supplying the area of ischaemia
- major-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)
- other specific causes of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse)
o Other stroke risk factor requiring immediate intervention that would preclude involvement in the trial
o Renal impairment (eGFR <35ml/min)
o Life expectancy <2 years
o Use of >2 antihypertensive drugs for an appropriate BP control
o Contraindications to the applied antihypertensive drugs as known
o Severe aortic stenosis
o Bilateral renal artery stenosis
o Severe arterial circulatory disorders
o Atrioventricular block II° or III° or sick sinus syndrome
o Heart failure (NYHA III or IV)
o Bradycardia, resting heart rate <50/min
o Bronchospastic diseases such as severe bronchial asthma
o Severe hepatic dysfunction such as liver cirrhosis
o Use of monoamine oxidase (MAO)-A-blockers
o Use of simvastatin >20mg/d
o Metabolic acidosis
o Disturbed electrolyte homeostasis such as hypercalcaemia, hypokalaemia, and hyponatraemia
o Symptomatic hyperuricaemia (gout)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified