Overview
The main objective of this randomized clinical trial is to evaluate the effects of the adapted Brazilian Cardioprotective Diet (DICA Br) supplemented or not with phytosterols and/or krill oil in patients with a probable or definitive diagnosis of familial hypercholesterolemia (FH) according to the the Dutch Lipid Clinic Network (Dutch MEDPED) criteria. In addition, the following will be considered secondary objectives: to perform participants´ whole genome sequencing (WGS); to evaluate the effects of the interventions on lipid profile biomarkers; to evaluate the frequency of mild, moderate and severe adverse events according to study groups; to identify the prevalence of subclinical atherosclerosis; to perform pharmacogenomic analysis; and to evaluate adherence rates according to study groups. In this study, 300 individuals will be randomly enrolled into four groups: 1) DICA Br adapted to the FH context (DICA-FH) + phytosterol placebo + krill oil placebo (control group); 2) DICA-FH + 2g/day of phytosterol + krill oil placebo; 3) DICA-FH + phytosterol placebo + 2g/day of krill oil; and 4) DICA-FH + 2g/day of phytosterol + 2g/day of krill oil.
Primary outcomes will be LDL-cholesterol for groups phytosterol vs. placebo and lipoprotein(a) for groups krill oil vs. placebo after 120 days of follow up.
Description
DICA-FH study is a superiority, factorial, and in parallel randomized placebo-controlled (double-dummy) clinical trial. The randomization will be in blocks stratified by research center, and the allocation ratio will be 1:1:1:1. Participants will come from at least 20 center sites in different Brazilian geographic regions.
Eligibility
Inclusion Criteria:
- Age ≥16 years;
- Definitive (certainty) or probable diagnosis of FH by the Dutch MEDPED criteria;
- Using one of the following treatment regimens for ≥6 weeks according to age:
>= 20 years -> simvastatin 40 mg; lovastatin 40 mg; pravastatin 80 mg; atorvastatin 20 mg; rosuvastatin 10 mg; pitavastatin 4 mg; fluvastatin 80 mg; atorvastatin 40- 80 mg; rosuvastatin 20 - 40 mg; atorvastatin 40 - 80 mg + ezetimibe 10mg; rosuvastatin 20 - 40 mg + ezetimibe 10mg; or simvastatin 40mg + ezetimibe 10mg.
16 to 19 years -> simvastatin 10 - 40 mg; lovastatin 10 - 40 mg; pravastatin 10 - 40 mg; atorvastatin 10 - 40 mg; rosuvastatin 5 - 40 mg; cholestyramine 4 to 16 mg; ezetimibe 10mg (in combination with statin).
Exclusion Criteria:
- Having a "possible" FH result according to the Dutch MEDPED criteria;
- TG ≥ 500mg/dL up to 6 months before screening for the study;
- Diagnosis of hypercholesterolemia due to a secondary cause recorded in the medical record;
- Food allergies (foods, dyes, preservatives);
- Contraindication to the use of phytosterols (for example: diagnosis of sitosterolemia);
- HIV positive on treatment with detectable viral load or AIDS;
- Chronic inflammatory or autoimmune diseases;
- Known liver disease, chronic kidney disease on dialysis or pancreatitis (acute and chronic);
- Cancer being treated or life expectancy < 6 months;
- Episode of acute coronary syndrome in the last 60 days;
- Chemical dependency/alcoholism;
- Chronic use of anti-inflammatories, anticonvulsants and immunosuppressive drugs;
- Use of PCSK9 inhibitors (alirocumab, evolocumab, inclisiran);
- Pregnancy or lactation;
- Individuals who are unable to perform an anthropometric assessment, at the discretion of the investigator;
- Grade III/severe obesity (body mass index [BMI] ≥40kg/m² for adults or percentile >99.9 or z-score >+3 according to WHO/2006 growth curves for BMI/Age indicator for adolescents);
- Use of dietary supplements that may interfere with the outcomes of interest (dietary fiber modules, n-3 PUFA, essential fatty acids);
- Participation in other randomized clinical trials;
- Refusal to participate in the study, due to failure to sign the Free and Informed Consent Form.