Clinical trial NCT06331195: An Adapted Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Familial Hypercholesterolemia (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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Familial Hypercholesterolemia
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
name: National Institute of Cardiology, Laranjeiras, Brazil
name: Instituto Dante Pazzanese de Cardiologia
First posted: 2024-03-26
Enrollment: 300
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: LDL-c
timeFrame: 120 days
measure: Lp(a)
timeFrame: 120 days
Secondary outcomes:
measure: TC
timeFrame: 120 days
measure: HDL-c
timeFrame: 120 days
measure: TG
timeFrame: 120 days
measure: VLDL
timeFrame: 120 days
measure: NHDL
timeFrame: 120 days
measure: CI I
timeFrame: 120 days
measure: CI II
timeFrame: 120 days
measure: TG/HDL-c
timeFrame: 120 days
measure: AI
timeFrame: 120 days
measure: ox-LDL
timeFrame: 120 days
measure: APOAI
timeFrame: 120 days
measure: APOB100
timeFrame: 120 days
measure: AE
timeFrame: 120 days
measure: Adherence
timeFrame: 120 days
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hcor
Study officials:
affiliation: Hospital do Coracao
name: Aline Marcadenti, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital do Coracao
name: Rachel Helena Machado, MSc
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Erlon O Abreu-Silva, MSc
role: STUDY_CHAIR
References: