Clinical trial NCT01821300: Down Syndrome Metabolic Health Study
Official title: Cardiometabolic Risk and Obesity in Adolescents With Down Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Down Syndrome
Trisomy 21
Keywords: Down syndrome
Philadelphia
The Children's Hospital of Philadelphia
Body composition
Obesity
Cardiovascular
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-04-01
Enrollment: 257
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited from primary care and speciality clinics, Trisomy 21 events, T21 interest groups, and referrals.

Brief summary: The purpose of this research study is to determine which measures best capture cardiovascular disease (CVD) risk and type 2 diabetes (T2DM) risk in children and adolescents with Down syndrome (DS).

We hypothesize that DS is associated with worse cardiometabolic risk factors for a given body mass index compared to controls. This difference arises at least in part, from increased fat tissue.

Detailed description: DS affects 1 per 800 births and is one of the most common causes of developmental disability in the US. Life expectancy for Down syndrome has increased significantly: estimated median survival in the US in 1997 was 49 years. DS is associated with an increased risk for obesity, with an estimated prevalence of 47-48% in adults and 30-50% in children with DS. Adolescents with DS are more likely to have increased adiposity compared to unaffected peers and may be at increased risk for obesity-related co-morbidities, such as type 2 diabetes and cardiovascular disease. How one defines obesity in DS is not clear. Individuals with DS have short stature and possibly increased adiposity, and the body mass index (BMI) used to define obesity for otherwise healthy populations may not accurately depict body fatness or capture cardiometabolic risk in DS.

Congenital heart disease (CHD) affects approximately 50% of individuals with DS; the National Institutes of Health Heart Lung and Blood Institute (NHLBI) Working Group on Obesity and Other Cardiovascular Risk Factors in Congenital Heart Disease highlighted the high prevalence of obesity in the setting of CHD, and called for studies to identify obesity measures that are more sensitive than BMI as well as studies of CVD risk prevention. Unfortunately, clinicians caring for obese adolescents with DS with or without CHD have little scientific evidence upon which to base guidance regarding cardiometabolic risk (CMR): data regarding CVD risk and prevalence of pre-diabetes and T2DM in obese adolescents with DS are lacking.

The measure of body fatness which best predicts CMR in DS is not known. We plan to compare BMI and other measures of body fatness in healthy controls and adolescents with DS to determine which measures best capture CVD and/or T2DM risk. These data will equip medical providers with the tools to better assess risk, initiate prevention measures, and guide screening in adolescents with DS.

Eligibility criteria: Inclusion Criteria:

* Both groups: Ages 10 - 20
* Both groups: Parental/guardian permission (informed consent) and if appropriate, child assent.
* Down syndrome group only: diagnosis of Down syndrome

Exclusion Criteria (both groups):

* Major organ system illness (such as leukemia), except for type 2 Diabetes
* Cyanotic congenital heart disease and/or pulmonary hypertension
* Medically unstable congenital heart disease
* Pregnancy
* Genetic syndrome known to affect glucose tolerance
* Familial hypercholesterolemia
* Currently treated with medications known to affect insulin sensitivity (other than diabetes agents in participants with type 2 diabetes)

Primary outcomes:
measure: Non-HDL Cholesterol
timeFrame: Study Visit 1
measure: Lipid Subparticles
timeFrame: Study Visit 1
measure: Lipid Subparticles (Size)
timeFrame: Study Visit 1
measure: Insulin Resistance
timeFrame: Study Visit 1
measure: Cardiometabolic Risk Biomarker Proteins
timeFrame: Study Visit 1
measure: Abnormal Glucose Tolerance
timeFrame: Study Visit 1
measure: Visceral Fat
timeFrame: Study Visit 1
measure: Body Mass Measures
timeFrame: Study Visit 1
measure: Left Ventricular Mass
timeFrame: Study Visit 1
measure: Pulse Wave Velocity
timeFrame: Study Visit 1
Secondary outcomes:
measure: Health Related Quality of Life - PedsQL
timeFrame: Study Visit 1
measure: Health Related Quality of Life - IWQOL
timeFrame: Study Visit 1
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Andrea Kelly, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. 2019 Aug;144(2):e20190137. doi: 10.1542/peds.2019-0137. Epub 2019 Jul 17.
citation: Kelly A, Magge SN, Walega R, Cochrane C, Pipan ME, Zemel BS, Cohen MS, Gidding SS, Townsend R. Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome. J Pediatr. 2019 Sep;212:79-86.e1. doi: 10.1016/j.jpeds.2019.04.059. Epub 2019 Jun 11.
citation: Kelly A, Gidding SS, Walega R, Cochrane C, Clauss S, Townsend RR, Xanthopoulos M, Pipan ME, Zemel BS, Magge SN, Cohen MS. Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome. Pediatr Cardiol. 2019 Feb;40(2):421-430. doi: 10.1007/s00246-018-2014-5. Epub 2018 Nov 1.
citation: Xanthopoulos MS, Walega R, Xiao R, Prasad D, Pipan MM, Zemel BS, Berkowitz RI, Magge SN, Kelly A. Caregiver-Reported Quality of Life in Youth with Down Syndrome. J Pediatr. 2017 Oct;189:98-104.e1. doi: 10.1016/j.jpeds.2017.06.073. Epub 2017 Jul 24.