Tadalafil as a treatment against cerebral small vessel disease and stroke.

Phase 1

• Conditions: Cerebral small vessel disease and stroke.; MedDRA version: 21.1Level: LLTClassification code 10070879Term: Cerebral small vessel ischemic diseaseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 22.1Level: PTClassification code 10076994Term: Lacunar strokeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-002329-27-DK
• Lead Sponsor: Herlev Gentofte Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-25
• Last Update Posted: 7 February 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

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 < 5 years ago; OR b) transient ischemic attack (TIA) with symptoms lasting < 24 hours AND with MR-DWI imaging performed acutely showing small vessel occlusion stroke, occurring < 5 years ago; OR c) TIA with symptoms lasting < 24 hours AND no acute MRI-DWI lesion but MRI/CT evidence of CSVD with old small vessel occlusion stroke(s) (involving =1.5cm) and/or confluent deep white matter hyperintensities (= grade 2 on Fazekas’s scale).
3.Age = 50 years.
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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 < 90 and/or diastolic BP < 50
10.Known severe renal impairment (eGFR < 30ml/min)
11.Known severe hepatic impairment (Child-Pugh > 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

Study & Design

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

Primary Outcome Measures

Name	Time	Method
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:<br>Cerebral blood perfusion<br>Cerebrovascular reactivity<br>Blood brain barrier function<br>Signs of cerebral small vessel disease on MRI<br>Cognition<br>Blood endothelial and inflammatory biomarkers<br>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.