SVDs@target: TREAT-SVDs
Research type
Research Study
Full title
TREAT-SVDs: EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases
IRAS ID
217583
Contact name
Alastair Webb
Contact email
Sponsor organisation
Klinikum der Universitaet Muenchen AoeR
Eudract number
2016-002920-10
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 4 months, 31 days
Research summary
Research Summary:
Chronic damage to small blood vessels in the brain are associated with up to 30% of strokes and up to 40% of dementia. High blood pressure is one of the most important risk factors for injury to small vessels in the brain, but it is currently not clear which blood pressure lowering drugs are best at improving small blood vessel function. We propose that the function of the small microvessels in the brain can be influenced by medication. This study will investigate the effects of three common blood pressure lowering tablets on the function of the brain‘s small blood vessels.TREAT-SVDs is a multicentre, non-commercial pharmaceutical study which will be performed in 3 different countries in Europe (Germany, the Netherlands, UK).
The study will be performed over 2 years and recruit 105 participants with either an acute small vessel stroke or cognitive problems plus underlying small vessel injury on brain scans. Each participant will be treated with each of three medications at standard doses (amlodipine 5-10mg, atenolol 50-100mg, losartan 50-100mg), titrated according to blood pressure, in place of their normal anti-hypertensive treatment, for 4 weeks, in random order. If required, a thiazide-like diuretic will be added. At baseline and on each medication, participants will undergo an MRI scan with inhalation of low-concentration carbon dioxide to measure reactivity of cerebral blood vessels, undergo cognitive testing at baseline, and throughout the study they will perform home blood pressure monitoring up to 4 times per day, with readings forwarded to a centralised server over a secured mobile phone network for regular review.
This study will determine the differential effects of three antihypertensive medications on reactivity of blood vessels in the brain and variability in blood pressure, to determine potential mechanisms by which they may have differential effects on stroke risk and progression of small vessel disease.Summary of Results:
TREAT-SVDs was a randomised, controlled, crossover designed trial to test whether 4 weeks of treatment with three commonly used medications to lower blood pressure (amlodipine, losartan and atenolol) improved function of the blood vessels in the brain in people with a condition known as cerebral small vessel disease, and secondly to test whether the drugs had different effects on their blood pressure measured at home. Small vessel disease is very commonly seen on brain scans as damage to the brain due to problems with the small blood vessels and is a common cause of stroke or dementia. Participants in TREAT-SVDs had to have evidence of one of these problems due to small vessel disease developing in later life (sporadic disease), or had to have a known genetic small vessel disease (CADASIL). To test the function of the blood vessels in the brain, participants underwent a specialised MRI scan during which they breathed in air mixed with carbon dioxide that stimulates blood vessels in the brain to open up to increase blood flow.
Between February 2018 and April 2022, 75 people with sporadic small vessel disease and 26 with CADASIL joined the study, of whom 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) had good quality data allowing us to test the effects of the drugs.
The function of the blood vessels in the brain in response to carbon dioxide was the same on the three different medications but there were differences in patients with CADASIL with improved function on amlodipine or losartan compared to atenolol in particularly This study demonstrated that it is possible to carry out this type of complex trial in this group of patients to test which drugs may improve the function of blood vessels in the brain, but did not confirm that one blood-pressure drug was better than another in the sporadic form of the disease. Further research will be required to confirm whether antihypertensive drug classes differentially affect people with CADASIL and whether they result in improved clinical outcomes in people with small vessel diseases.REC name
South Central - Oxford B Research Ethics Committee
REC reference
17/SC/0338
Date of REC Opinion
2 Aug 2017
REC opinion
Further Information Favourable Opinion