Clinical trial NCT01803178: The Effect of Plant Sterols on Vascular Function
Official title: The Effect of Plant Sterols on Vascular Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vascular Diseases
Hypercholesterolemia
Keywords: vascular function
plant sterols
blood lipids
Lead sponsor: Unilever R&D
Sponsor class: INDUSTRY
First posted: 2013-03-04
Enrollment: 240
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The main aim of the study is to investigate, in humans, the effect of plant sterols on vascular function by measuring flow-mediated dilation (FMD).

This study also aims to study the effect of plant sterols on pulse wave velocity (PWV), aortic augmentation index (Aix), central blood pressure (CBP), office blood pressure (BP), blood lipids and plasma plant sterol concentration. At last, the effects of plant sterols on z-scores of circulating biomarkers of endothelial dysfunction and low-grade inflammation will be assessed.

For all study outcomes, effect sizes and 95% confidence intervals will be estimated.

Hypothesis: Based on available evidence, it is hypothesized that plant sterols modestly increase FMD.

Detailed description: Plant sterols are well known for their LDL-cholesterol lowering benefit. Elevated cholesterol and especially LDL-cholesterol concentrations are established risk factors for coronary heart disease (CHD) and reducing these concentrations by dietary modification or drug treatment have been shown to reduce the risk of CHD. Direct evidence supporting a reduced risk of CHD has so far not been generated. Investigating the effects of consuming plant sterols on intermediate risk factors beyond cholesterol-lowering is therefore warranted.

Eligibility criteria: Inclusion Criteria:

* Apparently healthy men and post-menopausal women
* BMI ≥ 18 and ≤ 30 kg/m2.
* Aged between 40 - 65 years.
* Having elevated LDL-cholesterol concentrations at screening (130-190 mg/dL or 3.4-4.9 mmol/L).
* Blood pressure, heart rate, haematological and clinical chemical parameters within the normal reference range as judged by the research physician

Exclusion Criteria:

* Having (previous) cardiovascular event(s) (stroke, TIA, angina, myocardial infarction, heart failure), systemic inflammatory conditions or diabetes mellitus.
* Use of over-the-counter and prescribed medication which may interfere with study measurements (i.e. statins, ezetimibe, fibrates, diabetic drugs, ARB and ACE inhibitors), to be judged by the Principal Investigator.
* Use of medical treatment for elevated TG concentrations.
* Use of antibiotics in the three months prior to screening.
* Currently smoking or being a non-smoker for less than 6 months and reported use of any nicotine containing products in the 6 months prior to screening and/or during the study.

Primary outcomes:
measure: Change in flow-mediated dilation
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
Secondary outcomes:
measure: Change in pulse wave velocity
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
Other outcomes:
measure: Change in blood lipids
timeFrame: At baseline (after 4 weeks run-in period) and after 4, 8 and 12 weeks intervention
measure: Change in plasma plant sterols
timeFrame: At baseline (after 4 weeks run-in period) and after 4, 8 and 12 weeks intervention
measure: Change in plasma biomarkers of endothelial dysfunction and low-grade inflammation
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
measure: Change in aortic augmentation index
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
measure: Change in central blood pressure
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
measure: Change in office blood pressure
timeFrame: At baseline (after 4 weeks run-in period) and after 12 weeks intervention
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation
Study officials:
affiliation: Unilever Research & Development
name: Wieneke Koppenol, MSc
role: STUDY_DIRECTOR
References:
citation: Ras RT, Fuchs D, Koppenol WP, Schalkwijk CG, Otten-Hofman A, Garczarek U, Greyling A, Wagner F, Trautwein EA. Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects. J Nutr Sci. 2016 Dec 6;5:e44. doi: 10.1017/jns.2016.40. eCollection 2016.
citation: Ras RT, Koppenol WP, Garczarek U, Otten-Hofman A, Fuchs D, Wagner F, Trautwein EA. Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism. Nutr Metab Cardiovasc Dis. 2016 Apr;26(4):302-9. doi: 10.1016/j.numecd.2015.11.007. Epub 2015 Dec 12.
citation: Ras RT, Fuchs D, Koppenol WP, Garczarek U, Greyling A, Keicher C, Verhoeven C, Bouzamondo H, Wagner F, Trautwein EA. The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study. Am J Clin Nutr. 2015 Apr;101(4):733-41. doi: 10.3945/ajcn.114.102053.