Familial Hypercholesterolemia
Conditions
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; 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 multicenter 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.
Interventions
OTHERPlacebo phytosterol
Placebo of phytosterol, in the same quantity of the active phytosterol.
OTHERPlacebo krill oil
Placebo of krill oil, in the same quantity of the active krill oil.
DIETARY_SUPPLEMENTPhytosterol
2g/day will be provided to the participants, aiming to guarantee a minimum of 800mg/day of free phytosterols.
DIETARY_SUPPLEMENTKrill 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.
Sponsors
University of Sao Paulo
Hospital do Coracao
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LDL-c | 120 days | Low-density lipoprotein cholesterol, in mg/dL |
| Lp(a) | 120 days | Lipoprotein(a), in mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TG | 120 days | Fasting triglycerides, in mg/dL |
| VLDL | 120 days | Very low-density lipoprotein cholesterol, in mg/dL |
| NHDL | 120 days | Non-HDL cholesterol, in mg/dL, calculated according to the mathematical formula: CT - HDL-c |
| CI I | 120 days | Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c |
| CI II | 120 days | Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c |
| TG/HDL-c | 120 days | 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 |
| TC | 120 days | Total cholesterol, in mg/dL |
| ox-LDL | 120 days | Oxidized LDL, in µg/mL |
| APOAI | 120 days | Apolipoprotein A-I, in mg/dL |
| APOB100 | 120 days | Apolipoprotein B-100, in mg/dL |
| AE | 120 days | Adverse events (mild, moderate and severe), registered as percentage per study group |
| Adherence | 120 days | 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). |
| AI | 120 days | Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c |
| HDL-c | 120 days | High density lipoprotein cholesterol, in mg/dL |
Countries
Brazil
Contacts
Primary ContactAline Marcadenti, PhD
Backup ContactRachel Helena Machado, MSc
Outcome results
None listed