Effect of Tadalafil on Cerebral Large Arteries in Stroke

• Status: Completed
• Trial end date: 2017-08-04
• Target enrollment: 0
• Participant gender: All

Summary

In a double blind placebo-controlled cross-over study the effect of tadalafil on blood flow velocity in the large arteries of the brain, cortical brain oxygenation, peripheral endothelial function, and endothelial biomarkers will be tested in patients with lacunar stroke caused by cerebral small vessel disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Christina Kruuse
• Treatments: Tadalafil

Criteria

Inclusion Criteria:

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 5 months previously; OR

2. transient ischemic attack (TIA) lasting < 24 hours with limb weakness, hemi-sensory loss or dysarthria at least 5 months previously AND with MR DWI performed acutely showing lacunar infarction, OR if MRI is not performed within ten days of TIA, a lacunar infarction in an anatomically appropriate position is demonstrated on a subsequent MRI.

3. Age ≥ 50 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.

Exclusion Criteria:

1. Known diagnosis of dementia

2. Pregnancy or nursing

3. Cortical infarction (>1.5 cm maximum diameter)

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

5. eGFR < 30 ml/min/1,73m2

6. Severe hepatic impairment

7. History of Lactose intolerance

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

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

10. Body weight > 130kg

11. Uncontrolled cardiac failure

12. Persistent or paroxysmal atrial fibrillation

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

14. Uncontrolled COPD

15. Stroke or TIA within the last 5 months.

16. MRI not tolerated or contraindicated: MRI exclusion criteria: Participant has a cardiac pacemaker; recent surgery; vascular clips; metal implants or joint replacements that are not compatible with MRI; have had metal fragments in their eyes; has ever worked on a lathe; has shrapnel from a war injury; possibility of pregnancy

17. Known monogenic causes of stroke i.e. CADASIL

18. The patient does not wish to know important results from MRI

19. Unable to provide informed consent

20. Not possible to localise a. cerebri media bilaterally on inclusion day with Transcranial Doppler