Down Syndrome Metabolic Health Study

• ClinicalTrials.gov Identifier: NCT01821300
• Recruitment Status: Completed
• First Posted: April 1, 2013
• Results First Posted: January 9, 2019
• Last Update Posted: July 31, 2019
• Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Tracking Information

• First Submitted Date: March 27, 2013
• First Posted Date: April 1, 2013
• Results First Submitted Date: October 31, 2018
• Results First Posted Date: January 9, 2019
• Last Update Posted Date: July 31, 2019
• Study Start Date: February 2013
• Actual Primary Completion Date: August 25, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2018)

• Non-HDL Cholesterol [ Time Frame: Study Visit 1 ]
  Non-HDL cholesterol measured via fasting blood draw
• Lipid Subparticles [ Time Frame: Study Visit 1 ]
  Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
• Lipid Subparticles (Size) [ Time Frame: Study Visit 1 ]
  Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
• Insulin Resistance [ Time Frame: Study Visit 1 ]
  Insulin Resistance (HOMA-IR) was calculated as [fasting insulin (uIU/mL) x fasting glycemia (mmol/L)]/22.5
• Cardiometabolic Risk Biomarker Proteins [ Time Frame: Study Visit 1 ]
  hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1.
• Abnormal Glucose Tolerance [ Time Frame: Study Visit 1 ]
  Impaired fasting glucose (IFG) was defined as fasting glucose ≥ 100 mg/dl. Impaired glucose tolerance (IGT) was defined as 2-hour glucose 140-199 mg/dl measured as part of an oral glucose tolerance test.
• Visceral Fat [ Time Frame: Study Visit 1 ]
  Adiposity measured by Dual-energy X-ray absorptiometry
• Body Mass Measures [ Time Frame: Study Visit 1 ]
  Adiposity measured by Dual-energy X-ray absorptiometry
• Left Ventricular Mass [ Time Frame: Study Visit 1 ]
  Cardiac end organ injury assessed by echocardiography. Left Ventricular Mass (LVM) was measured by area/length method using the apical four-chamber and parasternal short-axis views. LVM was calculated as LV area × LV length × 1.05 × 5/6.
• Pulse Wave Velocity [ Time Frame: Study Visit 1 ]
  Cardiac end organ injury assessed by Pulse Wave Velocity (PWV)

Original Primary Outcome Measures (submitted: March 27, 2013)

Cardiometabolic risk factors [ Time Frame: day of visit ]

Non-HDL cholesterol, lipoprotein subclass particles, blood pressure, insulin resistance, inflammatory markers, and adipokines will be measured by blood test. Glucose tolerance will be measured by an Oral Glucose Tolerance Test in overweight subjects only. Adiposity will be measured by Dual-energy X-ray absorptiometry and anthropometric measurements. Cardiac end organ injury will be assessed by pulse wave velocity and echocardiography.

Current Secondary Outcome Measures (submitted: January 30, 2019)

• Health Related Quality of Life - PedsQL [ Time Frame: Study Visit 1 ]
  Caregiver-perception of his/her child's health-related QOL was assessed with the use of the parent-proxy report of the Pediatric Quality of Life Inventory (PedsQL) Version 4.0. Sub-scale scores are converted to a 0-100 scale so that greater scores indicate better QOL. Scale scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data). If more than 50% of the items in the scale are missing, the scale score is not computed. The Physical Health Summary Score (8 items) is the same as the Physical Functioning Scale. To create the Psychosocial Health Summary Score (15 items), the mean is computed as the sum of the items divided by the number of items answered in the Emotional, Social, and School Functioning Scales.
• Health Related Quality of Life - IWQOL [ Time Frame: Study Visit 1 ]
  Parent perception of the effects of weight on his/her child's QOL was assessed with a caregiver-proxy version of the Impact of Weight on Quality of Life - Kids (IWQOL-Kids) questionnaire. The IWQOL-Kids is a validated, 27-item, self-report measure of weight-related QOL for youth ages 11-19 years. It yields 4 subscales (Physical Comfort, Body Esteem, Social Life, and Family Relations) and a Total score, which have strong psychometric properties, discriminate among weight status groups, and are responsive to weight change. Scaled scores are standardized and range from 0 to 100, with greater scores representing better weight-related QOL.

Original Secondary Outcome Measures (submitted: March 27, 2013)

Psychosocial risk factors [ Time Frame: date of visit & 2 weeks following visit ]

Lifestyle (diet and physical activity)will be assessed via questionnaires on the date of visit. Participants will be asked to wear a physical activity armband at home for the 7 days following the visit, and to speak to a research nutritionist on the phone 3 times in the 2 weeks following the visit. Questionnaires will be done with participants and parents on the day of the visit to determine body image and quality of life.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Down Syndrome Metabolic Health Study
• Official Title: Cardiometabolic Risk and Obesity in Adolescents With Down Syndrome

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood serum will be retained.

• 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.

Condition

• Down Syndrome
• Trisomy 21

• Intervention: Not Provided

Study Groups/Cohorts

• Down syndrome
  No intervention occurred as this was a cross sectional observational study.
• Control
  No intervention occurred as this was a cross sectional observational study.

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2018): 257
• Original Estimated Enrollment (submitted: March 27, 2013): 250
• Actual Study Completion Date: August 25, 2017
• Actual Primary Completion Date: August 25, 2017 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01821300
• Other Study ID Numbers: 12-009233; 1R01HD071981-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Children's Hospital of Philadelphia
• Original Responsible Party: Same as current
• Current Study Sponsor: Children's Hospital of Philadelphia
• Original Study Sponsor: Same as current

Collaborators

• National Institutes of Health (NIH)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Andrea Kelly, MD, MSCE; Children's Hospital of Philadelphia

• PRS Account: Children's Hospital of Philadelphia
• Verification Date: July 2019