Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Patients With Familial Hypercholesterolemia

Effect of the Adapted Brazilian Cardioprotective Diet Supplemented With Phytosterols and/or Krill Oil in Patients With Familial Hypercholesterolemia: DICA-HF Pilot Study

The main objective of this pilot study is to evaluate the effects of the 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) identified by the Dutch Lipid Clinic Network (Dutch MEDPED) criteria. In addition, the following will be considered secondary objectives: to perform participants´ complete sequencing of the exome; to evaluate the effects of the interventions on lipid profile; to identify subclasses of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol; to perform untargeted lipidomic analyses; to evaluate the frequency of mild, moderate and severe adverse events according to study groups; and to evaluate both implementation components and adherence rates to the protocol, aiming to design a larger randomized trial. In this pilot study, between 48 and 76 individuals will be randomly enrolled into four groups: 1) DICA Br adapted to FH (DICA-HF) + phytosterol placebo + krill oil placebo (control group); 2) DICA-HF + 2g/day of phytosterol + krill oil placebo; 3) DICA-HF + phytosterol placebo + 2g/day of krill oil; and 4) DICA-HF + 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.

World Health Organization Universal Trial Number (WHO-UTN): U1111-1296-7102

DICA-HF pilot study is a superiority, factorial, and in parallel randomized placebo-controlled (double-dummy) clinical trial. The randomization will be in blocks of varying sizes stratified by research center, and the allocation ratio will be 1:1:1:1. Participants will come from at least 9 center sites in different Brazilian geographic regions.

Inclusion Criteria:

• Adult participants (age ≥20 years);
• Definitive (certainty) or probable diagnosis of FH by the Dutch MEDPED criteria;
• Using one of the following treatment regimens for ≥ 6 weeks: 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.

Exclusion Criteria:

• "Possible" diagnosis of FH according to the Dutch MEDPED criteria;
• Fasting triglycerides ≥ 500mg/dL;
• Diagnosis of hypercholesterolemia due to a secondary cause (hypothyroidism, nephrotic syndrome, etc.);
• Food allergies (food, dyes, preservatives);
• Contraindication to the use of phytosterols (for example: diagnosis of sitosterolemia);
• HIV positive in treatment/AIDS;
• Chronic inflammatory diseases;
• Liver disease or chronic kidney disease on dialysis;
• Cancer under treatment or life expectancy < 6 months;
• Episode of acute coronary syndrome in the last 60 days;
• Chemical dependency/alcoholism;
• Chronic use of anti-inflammatory, anticonvulsant and immunosuppressive drugs;
• Use of PCSK9 inhibitors (alirocumab and evolocumab);
• Pregnancy or lactation;
• Wheelchair users unable to undergo anthropometric assessment;
• Body mass index ≥40kg/m²;
• Use of dietary supplements that may interfere with the outcomes of interest;
• Participation in other randomized clinical trials;
• Refusal to participate in the study.