Familial Hypercholesterolemia
Conditions
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.
Interventions
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.
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
Sponsors
University of Sao Paulo
National Institute of Cardiology, Laranjeiras, Brazil
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
20 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lp(a) | 120 days | Lipoprotein(a), in mg/dL |
| Adherence | 120 days | 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). |
| LDL-c | 120 days | Low-density lipoprotein cholesterol, in mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CI I | 120 days | Castelli Index I, in mg/dL, calculated according to the mathematical formula: CT/HDL-c |
| TC | 120 days | Total cholesterol, in mg/dL |
| HDL-c | 120 days | High density lipoprotein cholesterol, in mg/dL |
| TG | 120 days | Fasting triglycerides, in mg/dL |
| TG/HDL-c | 120 days | TG/HDL-c ratio, in mg/dL, calculated according to the mathematical formula: TG/HDL-c |
| AI | 120 days | Atherogenic index, in mg/dL, calculated according to the mathematical formula: NHDL/HDL-c |
| ox-LDL | 120 days | Oxidized LDL, in µg/mL |
| AE | 120 days | Adverse events (mild, moderate and severe), registered as percentage per study group |
| Implementation | 120 days | 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. |
| CI II | 120 days | Castelli Index II, in mg/dL, calculated according to the mathematical formula: LDL-c/HDL-c |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subfractions | 120 days | Subclasses of LDL-c and HDL-c, in mg/dL |
| Lipidomics | 120 days | Analyses of untargeted lipidomic (all lipid species will be expressed in mg/dL) |
Countries
Brazil
Outcome results
None listed