An Adapted Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Familial Hypercholesterolemia (DICA-FH) (DICA-FH)

Effects of an Adapted Brazilian Cardioprotective Diet Supplemented or Not With Phytosterols and/or Krill Oil in Patients With Familial Hypercholesterolemia: the DICA-FH Randomized Clinical Trial

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; 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Other: Placebo phytosterol; Other: Placebo krill oil; Dietary supplement: Phytosterol; Dietary supplement: Krill oil

Detailed Description

DICA-FH study is a superiority, factorial, and in parallel multicenter 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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Belém, Brazil
    • OCARA
  • Boa Vista, Brazil
    • Centro Oncológico de Roraima
  • Brasília, Brazil
    • Instituto de Cardiologia e Transplantes do DF
  • Campo Grande, Brazil
    • Universidade do Mato Grosso do Sul
  • Cuiabá, Brazil
    • Universidade Federal do Mato Grosso
  • Fortaleza, Brazil
    • Hospital Oto Aldeota
  • Goiânia, Brazil
    • Universidade Federal de Goias
  • Macapá, Brazil
    • Universidade Federal do Amapá
  • Maceió, Brazil
    • Centro de Pesquisas Clínicas Dr. Marco Mota
  • Manaus, Brazil
    • Universidade Federal do Amazonas
  • Maringá, Brazil
    • Universidade Estadual de Maringá
  • Montes Claros, Brazil
    • Santa Casa de Montes Claros
  • Natal, Brazil
    • Centro de Estudos e Pesquisas em Moléstias Infecciosas
  • Palmas, Brazil
    • Universidade Federal do Tocantins
  • Petrolina, Brazil
    • Universidade Federal do Vale do São Francisco
  • Porto Velho, Brazil
    • Instituto de Pesquisa e Ensino em Saúde
  • Rio Branco, Brazil
    • Centro de Pesquisa Silvestre Santé
  • Rio de Janeiro, Brazil
    • Instituto Nacional de Cardiologia
  • Salvador, Brazil
    • Hospital Ana Nery
  • São Paulo, Brazil
    • Instituto Dante Pazzanese de Cardiologia
  • São Paulo, Brazil
    • Universidade Federal de Sao Paulo
  • São Paulo, Brazil
    • InCor
  • Teresina, Brazil
    • Centro de Pesquisa Cardiolima
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • Hcor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: DICA-FH + placebo; 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.	Other: Placebo phytosterol; Placebo of phytosterol, in the same quantity of the active phytosterol.; Other: Placebo krill oil; Placebo of krill oil, in the same quantity of the active krill oil.
Experimental: DICA-FH + 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.	Other: Placebo krill oil; Placebo of krill oil, in the same quantity of the active krill oil.; Dietary supplement: Phytosterol; 2g/day will be provided to the participants, aiming to guarantee a minimum of 800mg/day of free phytosterols.
Experimental: DICA-HF + 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.	Other: Placebo phytosterol; Placebo of phytosterol, in the same quantity of the active phytosterol.; Dietary supplement: Krill oil; 2g/day will be provided to the participants, aiming to guarantee a minimum of 400mg/day of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids.
Experimental: DICA-HF + phytosterol + 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.	Dietary supplement: Phytosterol; 2g/day will be provided to the participants, aiming to guarantee a minimum of 800mg/day of free phytosterols.; Dietary supplement: Krill oil; 2g/day will be provided to the participants, aiming to guarantee a minimum of 400mg/day of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-c	Low-density lipoprotein cholesterol, in mg/dL	120 days
Lp(a)	Lipoprotein(a), in mg/dL	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TC	Total cholesterol, in mg/dL	120 days
HDL-c	High density lipoprotein cholesterol, in mg/dL	120 days
TG	Fasting triglycerides, in mg/dL	120 days
VLDL	Very low-density lipoprotein cholesterol, in mg/dL	120 days
NHDL	Non-HDL cholesterol, in mg/dL, calculated according to the mathematical formula: CT - HDL-c	120 days
CI I	Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c	120 days
CI II	Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c	120 days
AI	Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c	120 days
ox-LDL	Oxidized LDL, in µg/mL	120 days
AE	Adverse events (mild, moderate and severe), registered as percentage per study group	120 days
TG/HDL-c	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	120 days
APOAI	Apolipoprotein A-I, in mg/dL	120 days
APOB100	Apolipoprotein B-100, in mg/dL	120 days
Adherence	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).	120 days

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Collaborators: University of Sao Paulo
• Investigators: Principal Investigator: Aline Marcadenti, PhD, Hospital do Coracao; Study Chair: Erlon O Abreu-Silva, MSc, Hospital do Coracao; Study Chair: Rachel Helena Machado, MSc, Hospital do Coracao

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Actual): February 13, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; Lipids; Biological Factors; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestanes; Sterols; Membrane Lipids; Phytochemicals; Phytosterols
• Other Study ID Numbers: DICA-HF_MAIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data supporting the findings of the DICA-FH study will be available upon reasonable request. Broader public access to the study database will be provided in due course, as soon as possible, in accordance with the Hcor Research Institute (IP-Hcor) data-sharing policy.
• IPD Sharing Time Frame: The data will be available in due course, as soon as possible, from the time the manuscript reporting the main study results is published, for an indefinite period.
• IPD Sharing Access Criteria: The study protocol, as well as the informed consent form and the statistical analysis plan will be made publicly available once the design paper is published. The clinical study report, analytic code, and clinical data will be available upon reasonable request, in accordance with the data-sharing policies of the IP-Hcor.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No