Unravelling the Impact of Diet on Cardiovascular Health in Heterozygous Familial Hypercholesterolemia.

NCT05181553 | Completed

• 1 other identifier: FH-Diet
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Familial Hypercholesterolemia; Nutrition, Healthy; Cholesterol, Elevated; Cholesterol; Metabolic Disorder; Cardiovascular Diseases

Keywords

familial hypercholesterolemia; diet; LDL-cholesterol; metabolome; cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• Post-diet differences in LDL-C levels.

  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.

  This analysis will compare LDL-C levels from plasma samples collected at the end (day 28) of each diet.

Secondary Outcomes (1)

• 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.

Other Outcomes (15)

• Post-diet differences in other atherogenic lipoproteins and lipids

  This analysis will compare levels of atherogenic lipoproteins and lipids measured from plasma samples collected at the end (day 28) of each diet

• Post-diet differences in other lipoproteins and lipids

  This analysis will compare levels of other lipoproteins and lipids measured from plasma samples collected at the end (day 28) of each diet

• Post-diet differences in fasting plasma glucose

  This analysis will compare levels of fasting plasma glucose (mmol/L) measured from plasma samples collected at the end (day 28) of each diet.

Study Arms (2)

Whole-food plant-based diet (WFPB diet)

EXPERIMENTAL

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.

Other: Whole-food plant based diet (WFPB diet)

Standard North American diet (SAD diet)

EXPERIMENTAL

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.

Other: Standard North American diet (SAD diet)

Interventions

Whole-food plant based diet (WFPB diet) OTHER

28-day fully controlled dietary intervention during which participants will receive a whole food plant-based diet that reflects the recommendations of Canada's Food Guide.

Whole-food plant-based diet (WFPB diet)

Standard North American diet (SAD diet) OTHER

28-day fully controlled dietary intervention during which participants will receive a diet that reflects the eating habits of Canadians.

Standard North American diet (SAD diet)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Genetically-defined HeFH
• Premenopausal women with a regular menstrual cycle for \>3 months
• Postmenopausal women (without hormone replacement)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

Institute on nutrition and functional foods, Laval University

Québec, Quebec, G1V0A6, Canada

Location

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia; Metabolic Diseases; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases

Study Officials

• Jean-Philippe Drouin-Chartier

  Laval University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The proposed research will combine a dietary RCT (objectives 1, 2) and a cohort investigation (objective 3). The dietary intervention will be undertaken as a crossover RCT at the INAF (Université Laval) in Quebec City. 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 (WFPB diet in further sections), and a standard North American diet (SAD diet; i.e. control diet), for 4 weeks each, and separated by a 4-week washout period. The first and second objective consist respectively to investigate the impact of a WFPB diet in place of a SAD on LDL-C concentrations and plasma metabolome. The third objective consist to evaluate the association between the plasma metabolomic signature of a diet low in red and processed meats and high in plant foods and cardiovascular disease risk.

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: January 6, 2022
• Study Start: January 10, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

CA (1)