The aim of the study is to obtain sufficient data on beneficial effects of Resveratrol on aortic aneurysm expansion rate and functional properties in patients with Marfan syndrome to justify a phase IIb or a phase III randomized trial.
ID
Source
Brief title
Condition
- Congenital cardiac disorders
- Cardiac and vascular disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
There are three main study parameters/endpoints:
1. A decrease in aortic aneurysm expansion rate in > 90% of the study subjects
as measured by echo between baseline (at timepoint of inclusion in the study)
and after twelve months of follow-up (after resveratrol treatment).
2. Any statistical significant beneficial change in aortic elasticity or aortic
wall shear rate as measured by magnetic resonance imaging (MRI) between
baseline (at timepoint of inclusion in the study) and after twelve months of
follow-up (after resveratrol treatment).
3. Any statistical significant beneficial change in endothelial function as
measured by Flow Mediated Dilatation (FMD)
Secondary outcome
1. To evaluate functional cardiac parameters by echocardiography in Marfan
patients upon treatment with resveratrol.
2. To evaluate changes in blood pressure/heart rate in patients with Marfan
syndrome treated with resveratrol.
3. To evaluate changes in endothelial cell function in patients with Marfan
syndrome treated with resveratrol by flow mediated dilation measurement (FMD).
4. To evaluate differences between Marfan patients who have had aortic
replacement and Marfan patients with a native aorta, before or after
resveratrol.
5. To evaluate differences between Marfan patients who have a haploinsufficient
(HI) FBN1 mutation or a dominant negative (DN) FBN1 mutation. Geneticists
determine the HI or DN status, however, skin cultures may provide conclusive
results when the mutation effect is unpredictable.
Background summary
We have shown that the food supplement Resveratrol inhibits aortic growth and
promotes aortic repair in Marfan Syndrome mice (doi:
10.1161/ATVBAHA.116.307841). The hypothesis is that Resveratrol treatment will
also be protective against aortic dilatation and functional deterioration in
humans with Marfan syndrome.
Study objective
The aim of the study is to obtain sufficient data on beneficial effects of
Resveratrol on aortic aneurysm expansion rate and functional properties in
patients with Marfan syndrome to justify a phase IIb or a phase III randomized
trial.
Study design
A pre-post observational design with evaluation of cardiovascular parameters
(primary and secondary outcomes) before and after 12 months of resveratrol
treatment.
Intervention
Resveratrol 500 mg/day for one year
Study burden and risks
Study subjects will be evaluated before and after 1 year of Resveratrol
treatment (2x) with various measurements. They will undergo echo, MRI, FMD,
blood sampling and skin biopsy. Furthermore, patients will complete a
Well-being questionnaire before and after 1 year of treatment.
Mijbergdreef 9
Amsterdam 1105 AZ
NL
Mijbergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Marfan patients with a known FBN1 mutation
- Between 18-50 years of age
- Native aortic root (n<=50) or aortic root replacement (n<=50)
- At least 2 echocardiography measurements and 1 MRI scan of the aorta prior to
the study
- Sinus rythm
Exclusion criteria
- More than one vascular prosthesis
- Aortic root diameter > 45 mm
- Aortic surgery likely within 6 months of inclusion
- Aortic surgery in the last 6 months prior to inclusion
- Aortic dissection
- Contraindications for MR imaging
- Mental retardation
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66127.018.18 |