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

Not Applicable

Active, not recruiting

• Conditions: Familial Hypercholesterolemia

• Registration Number: NCT05695937
• Lead Sponsor: Hospital do Coracao

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-01-13
• Study First Submitted QC: 2023-01-13
• Study First Posted: 2023-01-25
• Study Start: 2023-05-22
• Status Verified: 2023-08
• Primary Completion: 2023-12-31
• Last Update Submitted: 2024-03-19
• Last Update Posted: 2024-03-21
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 58

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
LDL-c	120 days	Low-density lipoprotein cholesterol, in mg/dL
Lp(a)	120 days	Lipoprotein(a), in mg/dL
Adherence	120 days	Adherence to treatment, evaluated by: attendance at consultations (at least 3 of the 4 planned study visits); 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).

Secondary Outcome Measures

Name	Time	Method
TC	120 days	Total cholesterol, in mg/dL
CI I	120 days	Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c
TG/HDL-c	120 days	TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/HDL-c
ox-LDL	120 days	Oxidized LDL, in µg/mL
Implementation	120 days	Implementation components, measured by: on-time recruitment rates; choice and adjustments of remote platform/media for center sites training; measures of participants´ engagement to interventions; and rates of loss to follow-up.
NHDL	120 days	Non-HDL cholesterol, in mg/dL, calculated according to the mathematical formula: CT - HDL-c
HDL-c	120 days	High density lipoprotein cholesterol, in mg/dL
TG	120 days	Fasting triglycerides, in mg/dL
CI II	120 days	Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c
AE	120 days	Adverse events (mild, moderate and severe), registered as percentage per study group
AI	120 days	Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c
VLDL	120 days	Very low-density lipoprotein cholesterol, in mg/dL

Trial Locations

Locations (9)

Hospital São José; 🇧🇷 Criciúma, Brazil

Hospital das Clínicas da Universidade Federal de Goiás; 🇧🇷 Goiânia, Brazil

Universidade Regional do Noroeste do Estado do Rio Grande do Sul; 🇧🇷 Ijuí, Brazil

Instituto Nacional de Cardiologia; 🇧🇷 Rio De Janeiro, Brazil

Hospital Ana Nery; 🇧🇷 Salvador, Brazil

Universidade Feevale; 🇧🇷 São Leopoldo, Brazil

Hcor; 🇧🇷 São Paulo, Brazil

InCor; 🇧🇷 São Paulo, Brazil

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, Brazil