Study Into Genetic Influence on Cholesterol Response to Dietary Fat

Cardiovascular Diseases Clinical Trial

— Satgene  

Official title:

Apolipoprotein E Genotype as a Determinant of LDL-cholesterol Response to Dietary Fat Manipulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01384032
• Other study ID #: WT085045MA
• Status: Completed
• Phase: N/A
• First received: June 20, 2011
• Last updated: June 27, 2011
• Start date: January 2009
• Est. completion date: May 2011

Study information

• Verified date: June 2011
• Source: University of Reading
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Cardiovascular disease (CVD) is recognised as one of the main causes of death in the western world. LDL- cholesterol ('bad' cholesterol) and other lipids (fats) are important CVD risk factors. Apolipoprotein E (apoE) is an important transporter of fats in the blood. ApoE comes in E2, E3 and E4 forms, depending on your genetic make up. Approximately 60% of the UK population are E3/E3, 25% E4 carriers and 15% E2 carriers. There is some evidence to suggest that an E4 genotype may put you at modestly higher risk of CVD. Furthermore although very inconclusive previous studies have suggested that E4 individuals are slightly more sensitive to the LDL-cholesterol modifying effects of dietary fats (saturated fat, total fat, fish oil) showing slightly, greater reductions when low levels of these fat are consumed, and greater increases when high levels of these fat are consumed. Therefore, the aims of the Satgene study is to examine the impact of modifications in dietary total fat and saturated fat intakes, alone and in combination with fish oil supplement on LDL-cholesterol and other blood lipids, in individuals with an E3 and E4 genotype. The levels of total fat and saturated fat used in the current study are within the range observed in a typical UK population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: May 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

Inclusion Criteria:

Men & women 35-70 years BMI 20-32 kg/m2 Haemoglobin (anaemia): 12.5-18.0g/l (men) and > 11.5-16g/l (women) Gamma GT (liver function) (< 80 IU/l), Triglyceride (between 1-4 mmol/l), Plasma total cholesterol (4.5-8 mmol/l) Glucose (World Health organisation recommend <7 mmol/L).

Exclusion Criteria:

• Females who are breast feeding, may be pregnant, or if child-bearing potential are not taking effective contraceptive precautions

• Likely to alter oral contraceptive or HRT usage during the course of the study

• Blood Pressure > 160/100 mm Hg (UK guidelines for stage 2 hypertension)

• Had suffered a myocardial infarction or stroke in the previous 12 months

• Hypertensive medication

• Diabetics type I and II

• Any volunteers on a weight reducing diet, or vegan/vegetarians as study requires consumption of dairy products and fish oils

• On high dose fish oil supplements (> 1g EPA + DHA per day)

• Elevated lipids requiring medication such as statins, fibrates, gall bladder problems or other abnormalities of fat metabolism

• Subjects not willing to make the necessary dietary changes during the study

• Subjects drinking excessive alcohol (UK recommendations/wk currently for men are, no more than 21 units of alcohol per week or more than four units in any one day. For women, no more than 14 units of alcohol per week or more than three units per day).

• Subjects who train at a high level, or attend more than 3 hours organised exercise classes per week

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Dietary Supplement:
• Low fat diet
Subjects were asked to consume a low fat diet for 8 weeks. Composition: 28% energy from fat, 8% energy from saturated fat, 55% energy from carbohydrate. Subjects were provided with low fat spread, cooking oil and snacks and asked to consume these in place of normally eaten equivalent foods. Subjects were asked to consume two extra portions of carbohydrate per day (e.g. two slices of bread, equivalent to 35g carbohydrate) and to consume low fat dairy products. Subjects also consumed 2g control oil per day during this period. Control oil comprised palm olein and soybean oil.
• Hgih saturated fat diet
Subjects were asked to consume a high saturated fat diet for 8 weeks. Composition: 38% energy from fat, 18% energy from saturated fat, 45% energy from carbohydrate. Subjects were provided with spread, cooking oil and snacks and asked to consume these in place of normally eaten equivalent foods. Subjects were asked to consume one less portion of carbohydrate per day (e.g. one slice of bread and to consume full fat dairy products. Subjects also consumed 2g control oil per day during this period. Control oil comprised palm olein and soybean oil.
• High saturated fat diet
Subjects were asked to consume a high saturated fat diet for 8 weeks. Composition: 38% energy from fat, 18% energy from saturated fat, 45% energy from carbohydrate. Subjects were provided with spread, cooking oil and snacks and asked to consume these in place of normally eaten equivalent foods. Subjects were asked to consume one less portion of carbohydrate per day (e.g. one slice of bread and to consume full fat dairy products. Subjects also consumed 6g DHA-rich oil per day during this period providing 3g DHA.

Locations

Country	Name	City	State
United Kingdom	Department of Food and Nutritional Sciences, University of Reading	Reading

Sponsors (2)

Lead Sponsor	Collaborator
University of Reading	Wellcome Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in low density lipoprotein cholesterol (LDL-C)		0, 8, 16, and 24 weeks	No
Secondary	Change in arterial stiffness	Arterial stiffness is a measure of vascular reactivity. This was assessed by Digital Volume Pulse using Pulse Trace PCA2 Machine (Micromedical, UK)	0, 8, 16, 24 weeks	No
Secondary	Change in fasting glucose		0, 8, 16, 24 weeks	No
Secondary	Change in fasting insulin		0, 8, 16, 24 weeks	No
Secondary	Change in fasting triglycerides (TAG)		0, 8, 16, 24 weeks	No
Secondary	Change in C-reactive protein (CRP)		0, 8, 16, 24 weeks	No
Secondary	Change in blood pressure		0, 8, 16, 24 weeks	No
Secondary	Change in body weight		0, 8, 16, 24 weeks	No
Secondary	Change in plasma phospholipid fatty acids		0, 8, 16, 24 weeks	No
Secondary	Change in total cholesterol		0, 8, 16, 24 weeks	No
Secondary	Change in high-density lipoprotein cholesterol (HDL)		0, 8, 16, 24 weeks	No
Secondary	Change in apolipoproteins B, CIII and E		0, 8, 16, 24 weeks	No
Secondary	Change in very low density lipoprotein (VLDL)		0, 8, 16, 24 weeks	No
Secondary	Change in chylomicrons (CM)		0, 8, 16, 24 weeks	No
Secondary	Change in inflammatory cytokine production		9, 8, 16, 24 weeks	No