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

Not Applicable
Active, not recruiting
Conditions
Familial Hypercholesterolemia
Interventions
Dietary Supplement: phytosterol
Other: Placebo krill oil
Other: Placebo phytosterol
Dietary Supplement: krill oil
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.

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
Arm && Interventions
GroupInterventionDescription
DICA-HF + phytosterolPlacebo krill oilParticipants 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.
DICA-HF + krill oilPlacebo phytosterolParticipants 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.
DICA-HF + phytosterol + krill oilkrill oilParticipants 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.
DICA-HF + placeboPlacebo phytosterolParticipants 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.
DICA-HF + phytosterolphytosterolParticipants 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.
DICA-HF + krill oilkrill oilParticipants 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.
DICA-HF + placeboPlacebo krill oilParticipants 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.
DICA-HF + phytosterol + krill oilphytosterolParticipants 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.
Primary Outcome Measures
NameTimeMethod
LDL-c120 days

Low-density lipoprotein cholesterol, in mg/dL

Lp(a)120 days

Lipoprotein(a), in mg/dL

Adherence120 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
NameTimeMethod
NHDL120 days

Non-HDL cholesterol, in mg/dL, calculated according to the mathematical formula: CT - HDL-c

TC120 days

Total cholesterol, in mg/dL

CI I120 days

Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c

TG/HDL-c120 days

TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/HDL-c

ox-LDL120 days

Oxidized LDL, in µg/mL

Implementation120 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.

HDL-c120 days

High density lipoprotein cholesterol, in mg/dL

TG120 days

Fasting triglycerides, in mg/dL

VLDL120 days

Very low-density lipoprotein cholesterol, in mg/dL

CI II120 days

Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c

AE120 days

Adverse events (mild, moderate and severe), registered as percentage per study group

AI120 days

Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c

Trial Locations

Locations (9)

Universidade Feevale

🇧🇷

São Leopoldo, Brazil

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

InCor

🇧🇷

São Paulo, Brazil

Hospital Ana Nery

🇧🇷

Salvador, Brazil

Hcor

🇧🇷

São Paulo, Brazil

Instituto Dante Pazzanese de Cardiologia

🇧🇷

São Paulo, Brazil

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