Perfusion by Arterial Spin Labelling Following Single Dose Tadalafil in Small Vessel Disease (PASTIS) Trial

1. Radiological evidence of cerebral small vessel disease defined as: MRI evidence of lacunar infarct(s) (≤ 1.5 cm maximum diameter) and/or confluent deep white matter leukoaraiosis (≥ grade 2 on Fazekas scale)

2. Clinical evidence of cerebral small vessel disease can be:

1. lacunar stroke syndrome with symptoms lasting >24 hours, occurring at least 6 months previously; OR:

2. transient ischaemic attack lasting < 24 hours with limb weakness, hemi-sensory loss or dysarthria at least 6 months previously AND with MRI DWI performed acutely showing lacunar infarction, OR if MRI is not performed within 10 days of TIA, a lacunar infarction in an anatomically appropriate position is demonstrated on a subsequent MRI

3. Age ≥ 55 years.

4. Imaging of the carotid arteries with Doppler ultrasound, CT angiography or MR angiography in the previous 12 months, demonstrating < 70% stenosis in both internal carotid arteries

1. Known diagnosis of dementia

2. Cortical infarction (>1.5 cm maximum diameter)

3. Systolic BP <90 and/or diastolic BP < 50

4. Creatinine Clearance<50ml/min

5. Severe hepatic impairment

6. History of Lactose intolerance

7. Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, vardenafil.

8. Concomitant use of alpha-blockers e.g. alfuzosin, doxazosin, indoramin, prazosin, tamsulosin, and terazosin can all increase the risk of postural hypotension.

9. Participants receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate

10. weight > 130kg

11 Uncontrolled cardiac failure

12. Persistent or paroxysmal atrial fibrillation

13. History of gastric ulceration

14. History of 'sick sinus syndrome' or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block

15. Uncontrolled COPD

16. Stroke or TIA within the last 6 months

17. MRI not tolerated or contra-indicated : MRI exclusion criteria -Participant has a cardiac pacemaker; recent surgery; vascular clips; metal implants or joint replacements; have had metal fragments in their eyes; has ever worked on a lathe; has shrapnel from a war injury; possibility of pregnancy

18. Known monogenic causes of stroke e.g.. CADASIL

19 Unable to provide informed consent

20. enrolled in another CTIMP study