Dyslipidemia of Obesity Intervention in Teens

Randomized, double-blind, placebo-controlled clinical trial of pitavastatin for 2 years comparing the effect of study drug versus placebo on vascular measures in at least 354 adolescents with excess adiposity and CDO (defined as high non-HDL-C + high triglycerides (TG)/HDL-C ratio or low HDL-C). Enrollment will take place over 36 months.

Inclusion criteria

• Boys and girls aged 10 to 19 years (with 2-year availability for study participation)
• BMI ≥85th percentile (using Centers for Disease Control (CDC) BMI charts)
• Fasting lipid profile x2 each with all of the following:

• LDL-C <160 mg/dL and ≥90 mg/dL, and
• TG (triglycerides) <500 mg/dL, and
• TG/HDL-C ratio ≥2.5 or HDL-C <45 mg/dL for boys or HDL-C <50 mg/dL for girls, and
• non-HDL-C ≥120 mg/dL
• Participant consent, or parental/guardian consent and participant assent

Exclusion criteria

• Current use of lipid lowering medication, growth hormone, systemic corticosteroids, cyclosporine, protease inhibitors, erythromycin, rifampin, colchicine, warfarin, second generation psychotropic drugs, oral isotretinoin; stable doses of stimulant or antidepressant therapy and antihypertensive medications will be accepted
• Known allergy or hypersensitivity to statin
• Patients who have had bariatric surgery or plan to have bariatric surgery during the trial
• Female who is pregnant, plans to become pregnant or is sexually active without contraception
• Uncontrolled stage 2 hypertension (systolic or diastolic blood pressure ≥95th percentile for age, sex and height percentile + 12 mmHg or ≥140/90, whichever is lower for participants <13 years of age; ≥140/90 for participants ≥13 years of age) confirmed after an appropriate evaluation
• Diabetes (type 1 or type 2) by American Diabetes Association criteria (fasting glucose ≥126 mg/dL, HbA1c ≥6.5%, random glucose ≥200 mg/dL, or 2-hour oral glucose tolerance testing glucose ≥200 mg/dL)
• Use of insulin sensitizing therapy
• Known renal insufficiency (known chronic renal disease, estimated glomerular filtration rate (GFR) <60 mL/min/1.73m2 at screening)
• Uncontrolled thyroid disease (TSH at screening >1.5x upper limit of normal, clinical or other laboratory evidence of hypothyroidism, or thyroid hormone therapy that has not been stable for 6 weeks prior to screening)
• Proteinuria suggestive of renal disease (more than trace together with an elevated urine protein:creatinine ratio as per local lab)
• Syndromic patients or patients with neurocognitive delay precluding adherence with study drug
• Liver disease other than non-alcoholic fatty liver disease (NAFLD) either diagnosed or suggested by alanine aminotransferase (ALT) ≥ 40 U/L, or severe NAFLD indicated by ALT ≥ 200 U/L
• Unexplained persistent elevated creatine kinase (CK) level >3x upper limit of normal
• Plans to leave the geographic area before completion of the anticipated 2 years of trial participation
• Any unstable medical or emotional condition or chronic disease that would preclude following the protocol or impact valid vascular measurement
• Admits to current smoking, current alcohol consumption