Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Patients With Familial Hypercholesterolemia (DICA-HF)

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

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Other: Placebo phytosterol; Other: Placebo krill oil; Dietary supplement: phytosterol; Dietary supplement: krill oil

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Criciúma, Brazil
    • Hospital São José
  • Goiânia, Brazil
    • Hospital Das Clinicas Da Universidade Federal De Goias
  • Ijuí, Brazil
    • Universidade Regional do Noroeste do Estado do Rio Grande do Sul
  • Rio de Janeiro, Brazil
    • Instituto Nacional de Cardiologia
  • Salvador, Brazil
    • Hospital Ana Nery
  • São Leopoldo, Brazil
    • Universidade Feevale
  • São Paulo, Brazil
    • Instituto Dante Pazzanese de Cardiologia
  • São Paulo, Brazil
    • Hcor
  • São Paulo, Brazil
    • InCor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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-HF + placebo; Participants allocated into this arm (n= 24) will receive the DICA Br adapted to FH (DICA-HF) 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-HF + phytosterol; Participants allocated into this arm (n= 24) will receive the DICA Br adapted to FH (DICA-HF) 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= 24) will receive the DICA Br adapted to FH (DICA-HF) 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= 24) will receive the DICA Br adapted to FH (DICA-HF) 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
Adherence	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).	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
TG/HDL-c	TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/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
Implementation	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.	120 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subfractions	Subclasses of LDL-c and HDL-c, in mg/dL	120 days
Lipidomics	Analyses of untargeted lipidomic (all lipid species will be expressed in mg/dL)	120 days

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Collaborators: University of Sao Paulo; National Institute of Cardiology, Laranjeiras, Brazil
• Investigators: Principal Investigator: Aline Marcadenti, PhD, Hospital do Coracao; Study Chair: Adriana B Carvalho, PhD, Instituto Nacional de Cardiologia; Study Chair: Alexandre B Cavalcanti, PhD, Hospital do Coracao; Study Chair: Angela C Bersch-Ferreira, PhD, Real e Benemerita Associacao Portuguesa de Beneficencia; Study Chair: Elizabeth S Torres, PhD, University of Sao Paulo; Study Chair: Erlon O Abreu-Silva, MSc, Hospital do Coracao; Study Chair: Geni R Sampaio, PhD, University of Sao Paulo; Study Chair: Julia P Krey, RDN, Hospital do Coracao; Study Chair: Karina L Negrelli, DVM, Hospital do Coracao; Study Chair: Luis Gustavo S Mota, RDN, Hospital do Coracao; Study Chair: Marcelo M Rogero, PhD, University of Sao Paulo; Study Chair: Maria Cristina Izar, PhD, Universidade Federal de Sao Paulo; Study Chair: Nagila T Damasceno, PhD, University of Sao Paulo; Study Chair: Patrícia V de Luca, MSc, Associação Brasileira de Hipercolesterolemia Familiar; Study Chair: Pedro M Barros, PhD, Hospital do Coracao; Study Chair: Renato N Santos, Stat, Hospital do Coracao; Study Chair: Rosana Perim, MSc, Hospital do Coracao; Study Chair: Thaís Martins, MD, Hospital De Clinicas De Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

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_PILOT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No