DO IT!: Dyslipidemia of Obesity Intervention in Teens

Sponsor

HealthCore-NERI (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02956590

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

122

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia Obesity	Drug: Pitavastatin Drug: Placebo	Phase 3

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 TG/HDL-C ratio or low HDL-C). Enrollment will take place over 36 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

122 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Dyslipidemia of Obesity Intervention in Teens Trial

Actual Study Start Date :

May 1, 2018

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Pitavastatin

Study Drug

Drug: Pitavastatin

Statin

Other Names:

Livalo

Placebo Comparator: Placebo

Placebo

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

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

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 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 Standard Fasting Lipid Profile (FLP) [2 years]
Change in time in standard fasting lipid profile
the effect of pitavastatin versus placebo on lipid measures [2 years]
Change in time in apolipoproteins
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 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 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 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 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 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)
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Boys and girls aged 10 to 19 years (with 2-year availability for study participation)
BMI ≥85th percentile (using CDC BMI charts)
Fasting lipid profile x2 each with all of the following:
LDL-C <160 mg/dL and ≥90 mg/dL, and
TG <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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nemours/Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
2	Children's National Health System	Washington	District of Columbia	United States	20010
3	Emory University School of Medicine	Atlanta	Georgia	United States	30322
4	Riley Hospital for Children at IU Health	Indianapolis	Indiana	United States	46202
5	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
6	Boston Children's Hospital	Boston	Massachusetts	United States	02114
7	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
10	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
12	Medical University of South Carolina	Charleston	South Carolina	United States	29425
13	Texas Children's Hospital	Houston	Texas	United States	77030
14	Primary Children's Hospital, University of Utah	Salt Lake City	Utah	United States	84108
15	University of Wisconsin	Madison	Wisconsin	United States	53792
16	The Hospital for Sick Children	Toronto	Ontario	Canada	M5g 1X8