Cerebral small vessel disease and stroke. MedDRA version: 21.1 Level: LLT Classification code 10070879 Term: Cerebral small vessel ischemic disease System Organ Class: 10029205 - Nervous system disorders MedDRA version: 22.1 Level: PT Classification code 10076994 Term: Lacunar stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Tadalafil Stada
Pharmaceutical Form: Capsule
INN or Proposed INN: Tadalafil
CAS Number: 171596-29-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Sponsors
Herlev Gentofte Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. MRI/computed tomography (CT) evidence of small vessel occlusion stroke(s)/lacunar stroke(s) (involving =2 cm in the acute phase and =1.5cm in the late phase) and/or confluent deep white matter hyperintensities (= grade 2 on Fazekas’s scale). 2. Clinical evidence of cerebral small vessel disease can be: a) small vessel occlusion stroke (lacunar stroke) syndrome with symptoms lasting > 24 hours, occurring =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Known diagnosis of dementia, medical treated dementia, or under investigaton for dementia 2. Pregnancy or nursing 3. Women of childbearing age not taking contraception 4. Known cortical infarction (> 1.5 cm maximum diameter) 5. Known carotid artery stenosis = 50 % with Doppler ultrasound, CT angiography, or MRI angiography diagnosed within the last five years 6. Known carotid or vertebral dissection as a cause of stroke 7. Stroke after carotid or heart surgery 8. Known hypercoagulable disease 9. Systolic BP B) 12. History of non-arthritic anterior ischemic optic neuropathy 13. Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, and vardenafil during trial period 14. Patients receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate 15. History of acute myocardial infarction in the last three months before trial intervention 16. Body weight > 130kg 17. Known cardiac failure (NYHA = II) 18. Known persistent or paroxysmal atrial fibrillation/flutter 19. History of “sick sinus syndrome” or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block (2nd of 3rd degree) 20. Other known cardiogenic cause of stroke 21. Contraindication to CO2 challage, eg severe respiratory disease 22. MRI not tolerated or contraindicated 23. Known monogenic causes of stroke i.e. CADASIL 24. Unable to provide informed consent 25. The participant does not wish to be informed about results from the MRI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We aim to investigate the feasibility of daily tadalafil for three months compared to placebo in cerebral small vessel disease patients with stroke. ;Secondary Objective: Secondary objectives are to investigate if daily tadalafil for three months compared to placebo have any effect on: Cerebral blood perfusion Cerebrovascular reactivity Blood brain barrier function Signs of cerebral small vessel disease on MRI Cognition Blood endothelial and inflammatory biomarkers Death in three and five years;Primary end point(s): Drop-out rate and proportion of participants achieving target dose assessed by diary and pharmacy tablet count. ;Timepoint(s) of evaluation of this end point: After one and three months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Cognitive evaluations will be assessed using the well validated Montreal Cognitive Assessment (MoCA) tool and Symbol Digit Modalities Test (SDMT). Different paper- and pencil tests and computerized tests will also be used to assess processing speed, attention, verbal and visual working memory, learning and memory, executive functions, and to estimate premorbid intelligence. • Adverse events will be registered during the trial period according to GCP. • Blood pressure and heart rate are registered at baseline, after one month, and three months. • Anatomical evaluations based on MRI will be performed at baseline and after three months intervention according to the STRIVE criteria. The following sequences will be included: 3D T1-weigthed, diffusion weighted imaging (DWI), T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion tensor imaging (DTI), MRI angiography, and susceptibility weighted imaging (SWI). • Register based outcome assessment with a composite measure of death, any ischemic event, hemorrhagic event or dementia per patient registry after three and five years respectively from end of trial. • Blood biomarkers - endothelial-, inflammatory-, and neuronal biomarkers and micro RNA. By use of MRI, dynamical cerebro-vascular evaluations will be performed at baseline and after three months in accordance with previous well documented MRI-protocols. The following MRI sequences will be used for dynamical evaluations: Pseudo-continuous arterial spin labeling (pCASL), Functional MRI (fMRI) - blood-oxygen-level dependent (BOLD), and dynamic contrast enhanced sequence (DCE). ;Timepoint(s) of evaluation of this end point: After three months. | — |
Countries
Denmark
Contacts
Public ContactChristina Kruuse
Herlev Gentofte Hospital
Outcome results
None listed