Clinical trial NCT05695937: Brazilian Cardioprotective Diet, Phytosterols and Krill Oil in Patients With Familial Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_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
First posted: 2023-01-25
Enrollment: 58
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: LDL-c
timeFrame: 120 days
measure: Lp(a)
timeFrame: 120 days
measure: Adherence
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: AE
timeFrame: 120 days
measure: Implementation
timeFrame: 120 days
Other outcomes:
measure: Subfractions
timeFrame: 120 days
measure: Lipidomics
timeFrame: 120 days
Locations:
city: Criciúma
country: Brazil
facility: Hospital São José
city: Goiânia
country: Brazil
facility: Hospital das Clínicas da Universidade Federal de Goiás
city: Ijuí
country: Brazil
facility: Universidade Regional do Noroeste do Estado do Rio Grande do Sul
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Cardiologia
city: Salvador
country: Brazil
facility: Hospital Ana Nery
city: São Leopoldo
country: Brazil
facility: Universidade Feevale
city: São Paulo
country: Brazil
facility: Hcor
city: São Paulo
country: Brazil
facility: InCor
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
Study officials:
affiliation: Hospital do Coracao
name: Aline Marcadenti, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Nacional de Cardiologia
name: Adriana B Carvalho, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Alexandre B Cavalcanti, PhD
role: STUDY_CHAIR
affiliation: Real e Benemérita Associação Portuguesa de Beneficência
name: Angela C Bersch-Ferreira, PhD
role: STUDY_CHAIR
affiliation: University of Sao Paulo
name: Elizabeth S Torres, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Erlon O Abreu-Silva, MSc
role: STUDY_CHAIR
affiliation: University of Sao Paulo
name: Geni R Sampaio, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Julia P Krey, RDN
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Karina L Negrelli, DVM
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Luis Gustavo S Mota, RDN
role: STUDY_CHAIR
affiliation: University of Sao Paulo
name: Marcelo M Rogero, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de São Paulo
name: Maria Cristina Izar, PhD
role: STUDY_CHAIR
affiliation: University of Sao Paulo
name: Nagila T Damasceno, PhD
role: STUDY_CHAIR
affiliation: Associação Brasileira de Hipercolesterolemia Familiar
name: Patrícia V de Luca, MSc
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Pedro M Barros, PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Renato N Santos, Stat
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Rosana Perim, MSc
role: STUDY_CHAIR
affiliation: Hospital de Clínicas de Porto Alegre
name: Thaís Martins, MD
role: STUDY_CHAIR
References: