Unravelling the Impact of Diet on Cardiovascular Health in Heterozygous Familial Hypercholesterolemia: a Metabolomic Approach.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Laval University
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Post-diet differences in LDL-C levels.
Study Overview
Brief Summary
The investigators will first conduct a fully controlled dietary randomized crossover trial (RCT) including 50 adults with HeFH to investigate the impact of a whole food plant-based (WFPB) diet low in red and processed meats and high in plant foods, reflecting Canada's Food Guide, in place of a standard North-American diet on LDL-cholesterol (LDL-C) levels and the plasma metabolome. Such a robust design will also lead to the identification an objective proxy to healthy diet adherence: the metabolomic signature. Secondly, by leveraging a cross-sectional cohort of adults with HeFH, the investigators will evaluate the relationship between the metabolomic signature of the healthy diet and cardiovascular disease risk factors in HeFH.
Detailed Description
The research combines a dietary RCT (objectives 1, 2) and a cohort investigation (objective 3), both including adults with genetically-defined HeFH.
The dietary intervention will be undertaken as a crossover RCT at the Institute on nutrition and functional foods (INAF, Laval University) in Quebec City. Participants (men and women with genetically-defined HeFH) will consume in a random order a fully-controlled whole food plant-based diet low in red and processed meats and high in plant foods, reflecting Canada's Food Guide principles (WFPB diet in further sections), and a standard North American diet (SAD diet; i.e. control diet), reflecting current dietary intakes of French-Canadians, for 4 weeks each, and separated by a 4-week washout period.
Once enrolled, participants will enter a 4-week run-in period at the beginning of which they will stop taking their lipid-lowering medication for the study duration (16 weeks). Other medications (e.g. anti-hypertensive drugs, oral contraceptives) will be allowed, but doses will have to remain constant during the study. At the end of the run-in, participants will provide a blood sample and complete a self-administered, validated web-based food-frequency questionnaire. Participants will be randomly assigned to either the WFPB-SAD or SAD-WFPB diet sequence, using a computer-assisted program. The randomization (1:1) will be stratified by sex (female vs male) and LDL-receptor (LDLR) genotype (receptor-negative vs others) in 8 blocks of 8 subjects. The two diets will be consumed for 4 weeks and separated by a 2- to 4-week washout period.
During diet phases, all meals and foods will be provided to ensure optimal diet control using a 7-day cyclic menu. The WFPB diet emphasizes low intakes of red and processed meats and high intakes of whole plant-based foods with water as the drink of choice, as per Canada's Food Guide. The SAD diet reflects current dietary intakes of the French-Canadian adult population in terms of foods, nutrients, and diet quality, as characterized in recent surveys conducted in an age- and a sex-representative sample of adults from the Province of Quebec. An experienced food technician will prepare the diets. Each food and ingredient will be weighed with a precision of ±0.1 g.
During the diet phases, participants will visit the INAF clinical research unit three times weekly (Monday, Wednesday, Friday) to collect their meals and had the option to eat on-site under supervision. At that time, they will also be given their evening meals and the next day's packaged breakfast to take home. Weekend meals will be provided at the Friday visits. A checklist will be provided to all participants to identify the consumed foods. Alcohol, vitamin supplements, and natural health products will not be allowed. Tea and coffee (black) will be allowed (≤2 servings/day without daily fluctuations). Participants will be instructed to maintain their usual physical activity level. At the end of each diet, fasting plasma samples will be collected in ethylenediaminetetraacetic acid (EDTA) tubes. Parts of the samples will be stored at -80℃ for future ancillary analyses. Participants' anthropometry, body composition (DEXA scan), and blood pressure will be measured. To incorporate gender aspects associated with the intervention in knowledge transfer activities, subjects' appreciation of the diets and appetite sensation will be assessed using visual analog scales filled after each meal on day 7 and 28 of each diet.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- Double (Investigator, Outcomes Assessor)
Masking Description
Subjects cannot be blinded to treatment allocation, but all laboratory analyses and outcomes will be assessed in a blinded fashion by research staff until the final analyses of the primary outcome are completed.
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Genetically-defined HeFH
- •Premenopausal women with a regular menstrual cycle for >3 months
- •Postmenopausal women (without hormone replacement)
Exclusion Criteria
- •Any cardiovascular disease-risk exacerbating conditions (age >60 years, homozygous FH, personal history of cardiovascular disease, diabetes/anti-diabetic drug use, severe obesity, unstable body weight for >3 months, uncontrolled hypertension, genetic hypertriglyceridemia),
- •Allergies/aversions to components of the experimental diets
- •Any condition that would interfere with optimal participation in the intervention.
Arms & Interventions
Whole-food plant-based diet (WFPB diet)
During 28 days, participants will receive the WFPB diet. The WFPB diet emphasizes low intakes of red and processed meats and high intakes of whole plant-based foods with water as the drink of choice, as per Canada's Food Guide. The number of portions of protein foods, whole-grains, fruits and vegetables to be served daily reflects the recommended ¼-¼-½ proportions. Regarding protein quality, vegetable proteins are served more often than animal proteins as stated in Canada's Food Guide. Weekly, red meat is served once and two days are meatless.
Intervention: Whole-food plant based diet (WFPB diet) (Other)
Standard North American diet (SAD diet)
During 28 days, participants will receive the SAD diet. The SAD diet reflects current dietary intakes of the French-Canadian adult population in terms of foods, nutrients, and diet quality, as characterized in recent surveys conducted in an age- and a sex-representative sample of adults from the Province of Quebec. Intakes of whole fruits and vegetables will be low; animal proteins, mostly red and processed meats, will be consumed more often than vegetable proteins; grains will be mostly refined; and ready-to-eat/ready-to-heat foods and sugary beverages will be served daily.
Intervention: Standard North American diet (SAD diet) (Other)
Outcomes
Primary Outcomes
Post-diet differences in LDL-C levels.
Time Frame: This analysis will compare LDL-C levels from plasma samples collected at the end (day 28) of each diet.
Investigators will compare the impact of a diet low in red and processed meats and high in plant foods in place of a standard North American diet on LDL-C concentrations among adults with HeFH.
Secondary Outcomes
- Post-diet differences in plasma metabolomics profiles.(This analysis will compare metabolomic profiles from plasma samples collected at the end (day 28) of each diet.)
- Post-diet differences in plasma metabolomics profiles.(This analysis will compare metabolomic profiles from plasma samples collected at the end (day 28) of each diet.)
Investigators
Jean-Philippe Drouin-Chartier
Professor
Laval University