An Adapted Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Familial Hypercholesterolemia (DICA-FH)
- Conditions
- Familial Hypercholesterolemia
- Interventions
- Other: Placebo phytosterolOther: Placebo krill oilDietary Supplement: PhytosterolDietary Supplement: Krill oil
- Registration Number
- NCT06331195
- Lead Sponsor
- Hospital do Coracao
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description DICA-FH + placebo Placebo krill oil Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus placebo of both phytosterol and krill oil during 120 days. DICA-FH + phytosterol Placebo krill oil Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of phytosterol and placebo of the krill oil during 120 days. DICA-HF + krill oil Placebo phytosterol Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of krill oil and placebo of phytosterol during 120 days. DICA-FH + placebo Placebo phytosterol Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus placebo of both phytosterol and krill oil during 120 days. DICA-FH + phytosterol Phytosterol Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of phytosterol and placebo of the krill oil during 120 days. DICA-HF + krill oil Krill oil Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of krill oil and placebo of phytosterol during 120 days. DICA-HF + phytosterol + krill oil Phytosterol Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of phytosterol and 2g/day of krill oil during 120 days. DICA-HF + phytosterol + krill oil Krill oil Participants allocated into this arm (n= 75) will receive the DICA Br adapted to FH (DICA-FH) plus 2g/day of phytosterol and 2g/day of krill oil during 120 days.
- Primary Outcome Measures
Name Time Method Lp(a) 120 days Lipoprotein(a), in mg/dL
LDL-c 120 days Low-density lipoprotein cholesterol, in mg/dL
- Secondary Outcome Measures
Name Time Method TC 120 days Total cholesterol, in mg/dL
TG 120 days Fasting triglycerides, in mg/dL
VLDL 120 days Very low-density lipoprotein cholesterol, in mg/dL
CI I 120 days Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c
APOAI 120 days Apolipoprotein A-I, in mg/dL
APOB100 120 days Apolipoprotein B-100, in mg/dL
Adherence 120 days Adherence to treatment, evaluated by: attendance at consultations (at least 3 of the 4 planned study visits); diet quality; plasma concentrations of phytosterols and erythrocyte levels of EPA/DHA fatty acids (identified by the difference between the last and the first study visits); and counting the consumed products under investigation (consumption of at least 80% of the capsules provided to the participants, regardless of the allocation group).
HDL-c 120 days High density lipoprotein cholesterol, in mg/dL
NHDL 120 days Non-HDL cholesterol, in mg/dL, calculated according to the mathematical formula: CT - HDL-c
ox-LDL 120 days Oxidized LDL, in µg/mL
CI II 120 days Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c
TG/HDL-c 120 days TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/HDL-c TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/HDL-c
AI 120 days Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c
AE 120 days Adverse events (mild, moderate and severe), registered as percentage per study group
Trial Locations
- Locations (1)
Hcor
🇧🇷São Paulo, Brazil