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

Familial Hypercholesterolemia Clinical Trial

— DICA-FH  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06331195
• Other study ID #: DICA-HF_MAIN
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Hospital do Coracao
• Contact: Aline Marcadenti, PhD
• Phone: +55 1130536611
• Email: amarcaden[@]hcor.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Other:
• Placebo phytosterol
Placebo of phytosterol, in the same quantity of the active phytosterol.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Hospital do Coracao	Instituto Dante Pazzanese de Cardiologia, National Institute of Cardiology, Laranjeiras, Brazil, University of Sao Paulo

Outcome

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