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

Familial Hypercholesterolemia Clinical Trial

— DICA-HF  

Official title:

Effect of the Adapted Brazilian Cardioprotective Diet Supplemented With Phytosterols and/or Krill Oil in Patients With Familial Hypercholesterolemia: DICA-HF Pilot Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05695937
• Other study ID #: DICA-HF_PILOT
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 22, 2023
• Est. completion date: July 2024

Study information

• Verified date: August 2023
• Source: Hospital do Coracao
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: July 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

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.

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

Locations

Country	Name	City	State
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	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

Sponsors (3)

Lead Sponsor	Collaborator
Hospital do Coracao	National Institute of Cardiology, Laranjeiras, Brazil, University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subfractions	Subclasses of LDL-c and HDL-c, in mg/dL	120 days
Other	Lipidomics	Analyses of untargeted lipidomic (all lipid species will be expressed in mg/dL)	120 days
Primary	LDL-c	Low-density lipoprotein cholesterol, in mg/dL	120 days
Primary	Lp(a)	Lipoprotein(a), in mg/dL	120 days
Primary	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	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	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	AE	Adverse events (mild, moderate and severe), registered as percentage per study group	120 days
Secondary	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