Dyslipidemia of Obesity Intervention in Teens
- Registration Number
- NCT02956590
- Lead Sponsor
- Carelon Research
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 122
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo Pitavastatin Pitavastatin Study Drug
- Primary Outcome Measures
Name Time Method the effect of pitavastatin versus placebo on vascular measures in at least 354 obese adolescents with combined dyslipidemia of obesity (CDO) 2 years Pulse wave velocity (PWV)
- Secondary Outcome Measures
Name Time Method the effect of pitavastatin versus placebo on Standard Fasting Lipid Profile (FLP) 2 years Change in time in standard fasting lipid profile
the effect of pitavastatin versus placebo on vascular measures in obese adolescents with combined dyslipidemia of obesity (CDO) 2 years carotid intima media thickness (CIMT)
the effect of pitavastatin versus placebo on prevalence of abnormal creatinine kinase (CK) tests 2 years Number of abnormal (yes/no) lab values based on creatinine kinase (CK) tests
the effect of pitavastatin versus placebo on Nuclear magnetic resonance (NMR) Spectroscopy Lipoprotein Particle Assessment 2 years Change in time in NMR Spectroscopy Lipoprotein Particle Assessment
the effect of pitavastatin versus placebo on prevalence of adverse events. 2 years Number of adverse events and other subject-reported symptoms (including neurocognitive and depressive symptoms).
the effect of pitavastatin versus placebo on composite outcome of Number of Participants With Abnormal Laboratory Values and/or Adverse Events 2 years 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
the effect of pitavastatin versus placebo on prevalence of abnormal changes in height 2 years Number of abnormal (yes/no) values based on change in height in time
the effect of pitavastatin versus placebo on vascular measures in at least 354 obese adolescents with combined dyslipidemia of obesity 2 years carotid artery stiffness
the effect of pitavastatin versus placebo on lipid measures 2 years Change in time in apolipoproteins
the effect of pitavastatin versus placebo on prevalence of abnormal Liver function tests (ALT, AST) 2 years Number of abnormal (yes/no) lab values based on Liver function tests (ALT, AST)
the effect of pitavastatin versus placebo on composite outcome of markers of glycemic control/development of diabetes 2 years Number of abnormal (yes/no) lab values based on markers of glycemic control/development of diabetes (fasting plasma glucose, HgbA1c)
the effect of pitavastatin versus placebo on composite outcome of abnormal change in surrogate markers of insulin sensitivity 2 years Number of abnormal (yes/no) lab values based on change in surrogate markers of insulin sensitivity (fasting insulin, C-peptide, HOMA-IR)
Trial Locations
- Locations (16)
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Riley Hospital for Children at IU Health
🇺🇸Indianapolis, Indiana, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Primary Children's Hospital, University of Utah
🇺🇸Salt Lake City, Utah, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Nemours/Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States