an adapted brazilian cardioprotective diet, phytosterols and krill oil in familial hypercholesterolemia (dica-fh)

Conditions: Familial Hypercholesterolemia

Summary: 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.

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 criteria:
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.