Dyslipidemia of Obesity Intervention in Teens

Study Overview
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Brief Summary
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This trial of pitavastatin will determine efficacy and safety in this high risk population and provide evidence for clinicians to target this treatable risk factor to achieve an impact on early atherosclerosis, and potentially achieve primary prevention of adult cardiovascular disease.

Detailed Description
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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.

Official Title
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Dyslipidemia of Obesity Intervention in Teens Trial

Conditions
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Dyslipidemia, Obesity

Intervention / Treatment
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* Drug: Pitavastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pitavastatin<br>Study Drug | Drug: Pitavastatin<br>* Statin<br>* Other names: Livalo;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effect of pitavastatin versus placebo on vascular measures in at least 354 obese adolescents with combined dyslipidemia of obesity (CDO) | Pulse wave velocity (PWV) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effect of pitavastatin versus placebo on vascular measures in obese adolescents with combined dyslipidemia of obesity (CDO) | carotid intima media thickness (CIMT) | 2 years | 
| the effect of pitavastatin versus placebo on vascular measures in at least 354 obese adolescents with combined dyslipidemia of obesity | carotid artery stiffness | 2 years | 
| the effect of pitavastatin versus placebo on Standard Fasting Lipid Profile (FLP) | Change in time in standard fasting lipid profile | 2 years | 
| the effect of pitavastatin versus placebo on lipid measures | Change in time in apolipoproteins | 2 years | 
| the effect of pitavastatin versus placebo on Nuclear magnetic resonance (NMR) Spectroscopy Lipoprotein Particle Assessment | Change in time in NMR Spectroscopy Lipoprotein Particle Assessment | 2 years | 
| the effect of pitavastatin versus placebo on composite outcome of Number of Participants With Abnormal Laboratory Values and/or Adverse Events | Number of abnormal (yes/no) lab values based on Liver function tests (ALT, AST); creatine kinase (CK), muscle symptoms; markers of glycemic control/development of diabetes (fasting plasma glucose, HgbA1c) and change in surrogate markers of insulin sensitivity (fasting insulin, C-peptide, Homeostatic model assessment Insulin resistance (HOMA-IR), 1/insulin, QUICKI); height velocity (change in height z score) and adverse events | 2 years | 
| the effect of pitavastatin versus placebo on prevalence of adverse events. | Number of adverse events and other subject-reported symptoms (including neurocognitive and depressive symptoms). | 2 years | 
| the effect of pitavastatin versus placebo on prevalence of abnormal Liver function tests (ALT, AST) | Number of abnormal (yes/no) lab values based on Liver function tests (ALT, AST) | 2 years | 
| the effect of pitavastatin versus placebo on prevalence of abnormal creatinine kinase (CK) tests | Number of abnormal (yes/no) lab values based on creatinine kinase (CK) tests | 2 years | 
| the effect of pitavastatin versus placebo on composite outcome of markers of glycemic control/development of diabetes | Number of abnormal (yes/no) lab values based on markers of glycemic control/development of diabetes (fasting plasma glucose, HgbA1c) | 2 years | 
| the effect of pitavastatin versus placebo on composite outcome of abnormal change in surrogate markers of insulin sensitivity | Number of abnormal (yes/no) lab values based on change in surrogate markers of insulin sensitivity (fasting insulin, C-peptide, HOMA-IR) | 2 years | 
| the effect of pitavastatin versus placebo on prevalence of abnormal changes in height | Number of abnormal (yes/no) values based on change in height in time | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dyslipidemia, obesity, pitavastatin, lipids