Clinical trial NCT01384032: Study Into Genetic Influence on Cholesterol Response to Dietary Fat
Official title: Apolipoprotein E Genotype as a Determinant of LDL-cholesterol Response to Dietary Fat Manipulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Keywords: CVD, LDL-C, apoE, SFA, DHA
Lead sponsor: University of Reading
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
First posted: 2011-06-28
Enrollment: 88
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in low density lipoprotein cholesterol (LDL-C)
timeFrame: 0, 8, 16, and 24 weeks
Secondary outcomes:
measure: Change in arterial stiffness
timeFrame: 0, 8, 16, 24 weeks
measure: Change in fasting glucose
timeFrame: 0, 8, 16, 24 weeks
measure: Change in fasting insulin
timeFrame: 0, 8, 16, 24 weeks
measure: Change in fasting triglycerides (TAG)
timeFrame: 0, 8, 16, 24 weeks
measure: Change in C-reactive protein (CRP)
timeFrame: 0, 8, 16, 24 weeks
measure: Change in blood pressure
timeFrame: 0, 8, 16, 24 weeks
measure: Change in body weight
timeFrame: 0, 8, 16, 24 weeks
measure: Change in plasma phospholipid fatty acids
timeFrame: 0, 8, 16, 24 weeks
measure: Change in total cholesterol
timeFrame: 0, 8, 16, 24 weeks
measure: Change in high-density lipoprotein cholesterol (HDL)
timeFrame: 0, 8, 16, 24 weeks
measure: Change in apolipoproteins B, CIII and E
timeFrame: 0, 8, 16, 24 weeks
measure: Change in very low density lipoprotein (VLDL)
timeFrame: 0, 8, 16, 24 weeks
measure: Change in chylomicrons (CM)
timeFrame: 0, 8, 16, 24 weeks
measure: Change in inflammatory cytokine production
timeFrame: 9, 8, 16, 24 weeks
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: Department of Food and Nutritional Sciences, University of Reading
Study officials:
affiliation: University of Reading
name: Julie A Lovegrove, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chouinard-Watkins R, Conway V, Minihane AM, Jackson KG, Lovegrove JA, Plourde M. Interaction between BMI and APOE genotype is associated with changes in the plasma long-chain-PUFA response to a fish-oil supplement in healthy participants. Am J Clin Nutr. 2015 Aug;102(2):505-13. doi: 10.3945/ajcn.114.103507. Epub 2015 Jun 17.
citation: Carvalho-Wells AL, Jackson KG, Lockyer S, Lovegrove JA, Minihane AM. APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults. Am J Clin Nutr. 2012 Dec;96(6):1447-53. doi: 10.3945/ajcn.112.043240. Epub 2012 Nov 7.
citation: Lockyer S, Tzanetou M, Carvalho-Wells AL, Jackson KG, Minihane AM, Lovegrove JA. SATgenepsilon dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods. Br J Nutr. 2012 Nov 14;108(9):1705-13. doi: 10.1017/S0007114511007082. Epub 2012 Jan 16.