Effect of Plant Sterols on the Lipid Profile of Patients With Hypercholesterolaemia

Study Overview
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Brief Summary
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Background information Studies have been conducted on supplementing the daily diet with plant sterol ester-enriched milk derivatives in order to reduce LDL-cholesterol levels and, consequently, cardiovascular risk. However, clinical practice guidelines on hypercholesterolaemia state that there is not sufficient evidence to recommend their use in subjects with hypercholesterolaemia. The null hypothesis establishes that there is no relationship between the decrease in blood LDL-cholesterol levels and the consumption of stanol ester enriched liquid yoghurt. The alternative hypothesis establishes a relationship between such consumption and the incidence of the primary variable. The main objective of this study is to determine the efficacy of the intake of 2 g of plant sterol esters a day in lowering LDL-cholesterol levels in patients diagnosed with hypercholesterolaemia. The specific objectives are: 1) to quantify the efficacy of the daily intake of plant sterol esters in lowering LDL-cholesterol, total cholesterol and cardiovascular risk in patients with hypercholesterolaemia; 2) to evaluate the occurrence of adverse effects of the daily intake of plant sterol esters; 3) to identify the factors that determine a greater reduction in lipid levels in subjects receiving plant sterol ester supplements. Study design Randomised, double-blind, placebo controlled experimental trial carried out at family doctors' surgeries at three health centres in the Health Area of Albacete (Spain). The study subjects will be adults diagnosed with limit or defined hypercholesterolaemia and who have LDL cholesterol levels of 130 mg/dl or over. A dairy product in the form of liquid yoghurt containing 2 g of plant sterol ester per container will be administered daily after the main meal, for a period of 24 months. The control group will receive a daily unit of yogurt not supplemented with plant sterol esters that has a similar appearance to the enriched yoghurt. The primary variable is the change in lipid profile at 1, 3, 6, 12, 18 and 24 months. The secondary variables are: change in cardiovascular risk, adherence to the dairy product, adverse effects, adherence to dietary recommendations, frequency of food consumption, basic physical examination data, health problems, lipid-lowering medication, physical activity, smoking habits and socio-demographic variables.

Official Title
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EFFECT OF PLANT STEROLS ON THE LIPID PROFILE OF PATIENTS WITH HYPERCHOLESTEROLAEMIA. RANDOMISED, EXPERIMENTAL STUDY

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: Plant stanol esters


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with limit hypercholesterolaemia (total cholesterol 200-249 mg/dl) or defined hypercholesterolaemia (total cholesterol equal to or above 250 mg/dl) who have LDL-cholesterol levels equal to or above 130 mg/dl Subjects aged 18 years or over attending the participating health centres Subjects who give their consent to participate after being informed of the study objectives Exclusion Criteria: Known hypersensitivity to sterol esters or to the other components of the food that contains them (liquid yoghurt) Contraindication for treatment with sterol esters or any of the components of the food Physical disability that hinders collaboration Significant chronic organic or psychiatric disease Not obtaining informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liquid yoghurt with plant stanol esters<br>Dairy product in the form of liquid yoghurt, marketed in Spain, that contains 2 g per container of plant stanol esters: sitostanol and campestanol (AHA recommended dose - 1.5 to 3 g). It also contains: proteins 1.8 g, carbohydrates 9.8 g, fat 1.4 g, plant stanol 2 g, vitamin B6 0.6 mg, folic acid 60 mg. | Dietary Supplement: Plant stanol esters<br>* The administration of a dairy product in the form of liquid yoghurt, marketed in Spain, that contains 2 g per container of plant stanol esters: sitostanol and campestanol (AHA recommended dose - 1.5 to 3 g). The enriched product and the placebo will have the same characteristics (composition and outward appearance), but the placebo will not contain stanol esters. The dose will be one container a day, after the main meal, for 24 months. The participants may continue with their previously prescribed lipid-lowering treatment and new treatment needed for this disease or for other diseases. Composition per container: proteins 1.8 g, carbohydrates 9.8 g, fat (except stanol) 1.4 g, plant stanol 2 g, vitamin B6 0.6 mg, folic acid 60 mg. The control group will receive one unit a day of yoghurt not supplemented with stanol esters that has a similar appearance to the enriched yoghurt.<br>|
| Placebo Comparator: Yoghurt without plant stanol esters<br>Composition per container: proteins 1.8 g, carbohydrates 9.8 g, fat (except stanol) 1.4 g, plant stanol 2 g, vitamin B6 0.6 mg, folic acid 60 mg. | Dietary Supplement: Plant stanol esters<br>* The administration of a dairy product in the form of liquid yoghurt, marketed in Spain, that contains 2 g per container of plant stanol esters: sitostanol and campestanol (AHA recommended dose - 1.5 to 3 g). The enriched product and the placebo will have the same characteristics (composition and outward appearance), but the placebo will not contain stanol esters. The dose will be one container a day, after the main meal, for 24 months. The participants may continue with their previously prescribed lipid-lowering treatment and new treatment needed for this disease or for other diseases. Composition per container: proteins 1.8 g, carbohydrates 9.8 g, fat (except stanol) 1.4 g, plant stanol 2 g, vitamin B6 0.6 mg, folic acid 60 mg. The control group will receive one unit a day of yoghurt not supplemented with stanol esters that has a similar appearance to the enriched yoghurt.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipid profile | Lipid levels will be measured in both plasma and capillary blood at the initial visit. The validity of the capillary blood lipid levels can be checked with the Cardiochek analyser (by total cholesterol, HDL-cholesterol and triglyceride strips, and subsequent calculation of LDL-cholesterol using the Friedewald formula). The measurements at 3, 12 and 24 months will be in plasma. At 1, 6 and 18 months they will only be in capillary blood. | At 1, 3, 6, 12, 18 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiovascular risk | SCORE and REGICOR tables will be used for the evaluation. | At 1, 3, 6, 12, 18 and 24 months | 
| Adherence to the dairy product (liquid yoghurt) | By self-report and Morisky-Green scale, which determines the degree of coincidence between the patient's behaviour and the doctor's advice (a non-complier is one who answers one of the four questions of the scale inappropriately). | At 1, 3, 6, 12, 18 and 24 months | 
| Adverse events | Considered as any undesirable event in any patient included in the study, even though it does not have a causal relation with the product. Known adverse events of phytosterols in the diet at the proposed doses: occasionally mild digestive alterations. | At 1, 3, 6, 12, 18 and 24 months | 
| Adherence to the dietary recommendations | 5-point Likert scale | At 1, 3, 6, 12, 18 and 24 months | 
| Frequency of food intake | Using the CDC-FFQ questionnaire, validated in Spain (Aguirre, 2008) considered appropriate to classify the subjects according to their intake of food and nutrients. | At 1, 3, 6, 12, 18 and 24 months | 
| Occurrence of cardiovascular events | Ischaemic heart disease, atherothrombotic cerebrovascular disease, heart failure and peripheral artery disease. -Weight, height, body mass index (BMI): classification of subjects according to degree of obesity. | At 1, 3, 6, 12, 18 and 24 months | 
| Weight, height, body mass index (BMI) | Classification of subjects according to degree of obesity. | At 1, 3, 6, 12, 18 and 24 months | 
| Physical activity | Amount of aerobic exercise (active if performs aerobic exercise for 30 minutes or more, three or more times a week, partially active if exercises with less frequency and for less time that this and inactive when does not perform any type of exercise). | At 1, 3, 6, 12, 18 and 24 months | 
| Smoking habit | Considered smoker if answers yes to the question do you smoke? | At 1, 3, 6, 12, 18 and 24 months | 
| Systolic and diastolic blood pressure (two measurements): | The result will be the mean of the two measurements. | At 1, 3, 6, 12, 18 and 24 months | 
| Health problems | (WONCA ICPC-2) | At 1, 3, 6, 12, 18 and 24 months | 
| Lipid-lowering pharmacological treatment. | Whether taking lipid-lowering pharmacological treatment. | At 1, 3, 6, 12, 18 and 24 months | 
| Socio-demographic data | Age, gender, marital status, educational level and social class based on occupation (National Classification of Occupations). | Initial visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, Lipids, Cardiovascular disease, Risks factors, Primary Care