Dyslipidemia of Obesity Intervention in Teens (DO IT!)

Dyslipidemia of Obesity Intervention in Teens Trial

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Dyslipidemia
• Intervention / Treatment: Drug: Placebo; Drug: Pitavastatin

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.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• United States
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/Alfred I DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at IU Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Primary Children's Hospital, University of Utah
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: Pitavastatin; Study Drug	Drug: Pitavastatin; Statin; Other Names: Livalo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): April 21, 2023
• Study Completion (Actual): April 21, 2023

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: November 3, 2016
• First Posted (Estimated): November 6, 2016

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: obesity; lipids; dyslipidemia; pitavastatin
• Additional Relevant MeSH Terms: Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Lipid Metabolism Disorders; Obesity; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pitavastatin
• Other Study ID Numbers: PHN DO IT!

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No