Not provided
Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HD071981-01A1 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Non-HDL Cholesterol | Non-HDL cholesterol measured via fasting blood draw | Study Visit 1 |
| Lipid Subparticles | Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1. | Study Visit 1 |
| Lipid Subparticles (Size) | Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1. | Study Visit 1 |
| Insulin Resistance | Insulin Resistance (HOMA-IR) was calculated as [fasting insulin (uIU/mL) x fasting glycemia (mmol/L)]/22.5 | Study Visit 1 |
| Cardiometabolic Risk Biomarker Proteins | hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1. | Study Visit 1 |
| Abnormal Glucose Tolerance | 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. | Study Visit 1 |
| Visceral Fat | Adiposity measured by Dual-energy X-ray absorptiometry | Study Visit 1 |
| Body Mass Measures |
| Measure | Description | Time Frame |
|---|---|---|
| Health Related Quality of Life - PedsQL | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria (both groups):
Not provided
Not provided
Participants will be recruited from primary care and speciality clinics, Trisomy 21 events, T21 interest groups, and referrals.
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Andrea Kelly, MD, MSCE | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States | ||
| The Children's Hospital of Philadelphia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31315916 | Derived | 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. | |
| 31201031 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Down Syndrome | 154 participants ages 10-20 years old. No intervention occurred as this is a cross-sectional observational study. |
| FG001 | Control | 103 age-, sex-, race-, ethnicity-, and BMI percentile-matched control subjects. No intervention occurred as this is a cross-sectional observational study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Participants from the Down syndrome and control groups were matched on BMI percentile, age, race, ethnicity, and sex.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Down Syndrome | Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group. |
| BG001 | Control | Our goal is to enroll 105 typically developing controls, who are matched to the Down syndrome group by age, sex, race, ethnicity, and BMI-z score. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Non-HDL Cholesterol | Non-HDL cholesterol measured via fasting blood draw | Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0 | Posted | Median | Inter-Quartile Range | mg/dl | Study Visit 1 |
|
Adverse Events are monitored throughout participants' roughly 6 hour study visit, and for the 2 weeks following study visit while participants are wearing accelerator armbands and completing dietary recalls at home.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Down Syndrome | Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin irritation | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Skin irritation due to physical activity armband wear. If irritation occurred armband wear was discontinued. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Andrea Kelly | The Children's Hopsital of Philadelphia | 215590-3174 | kellya@email.chop.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 21, 2017 | Oct 8, 2018 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D004314 | Down Syndrome |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Blood serum will be retained.
Adiposity measured by Dual-energy X-ray absorptiometry
| Study Visit 1 |
| Left Ventricular Mass | 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. | Study Visit 1 |
| Pulse Wave Velocity | Cardiac end organ injury assessed by Pulse Wave Velocity (PWV) | Study Visit 1 |
| Study Visit 1 |
| Health Related Quality of Life - IWQOL | 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. | Study Visit 1 |
| Philadelphia |
| Pennsylvania |
| 19104 |
| United States |
| 30386863 | Derived | 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. |
| 28751125 | Derived | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI Percentile | Height & weight were measured and entered into the online CDC BMI Calculator for children and teens to determine percentile. | Mean | Standard Deviation | percentile |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Primary | Lipid Subparticles | Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1. | Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0. | Posted | Median | Inter-Quartile Range | nmol/L | Study Visit 1 |
|
|
|
| Primary | Lipid Subparticles (Size) | Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1. | Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0. | Posted | Median | Inter-Quartile Range | nm | Study Visit 1 |
|
|
|
| Primary | Insulin Resistance | Insulin Resistance (HOMA-IR) was calculated as [fasting insulin (uIU/mL) x fasting glycemia (mmol/L)]/22.5 | Participants excluded from insulin resistance analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=147, Controls=103. | Posted | Median | Inter-Quartile Range | HOMA-IR | Study Visit 1 |
|
|
|
| Primary | Cardiometabolic Risk Biomarker Proteins | hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1. | Participants excluded from analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0. | Posted | Median | Inter-Quartile Range | ng/dL | Study Visit 1 |
|
|
|
| Primary | Abnormal Glucose Tolerance | 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. | Participants completed an oral glucose tolerance test if they were in the overweight or obese categories: DS n=96, Control n=64. | Posted | Count of Participants | Participants | Study Visit 1 |
|
|
|
| Primary | Visceral Fat | Adiposity measured by Dual-energy X-ray absorptiometry | Posted | Median | Inter-Quartile Range | cm^2 | Study Visit 1 |
|
|
|
| Primary | Body Mass Measures | Adiposity measured by Dual-energy X-ray absorptiometry | Posted | Median | Inter-Quartile Range | g | Study Visit 1 |
|
|
|
| Primary | Left Ventricular Mass | 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. | LVM was available in 136 adolescents with DS (60M/76F) and 101nonDS controls (41M/60F). | Posted | Median | Inter-Quartile Range | g | Study Visit 1 |
|
|
|
| Primary | Pulse Wave Velocity | Cardiac end organ injury assessed by Pulse Wave Velocity (PWV) | PWV was available in 129 adolescents with DS and 97 controls | Posted | Median | Inter-Quartile Range | m/s | Study Visit 1 |
|
|
|
| Secondary | Health Related Quality of Life - PedsQL | 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. | Posted | Mean | Standard Deviation | score on a scale | Study Visit 1 |
|
|
|
| Secondary | Health Related Quality of Life - IWQOL | 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. | Posted | Mean | Standard Deviation | score on a scale | Study Visit 1 |
|
|
|
| 0 |
| 154 |
| 0 |
| 154 |
| 7 |
| 154 |
| EG001 | Control | Our goal is to enroll 105 typically developing controls, who are matched to the Down syndrome group by age, sex, race, ethnicity, and BMI-z score. | 0 | 103 | 0 | 103 | 3 | 103 |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment | Vomiting in reaction to glucola ingestion associated with oral glucose tolerance test. |
|
| Fainting | General disorders | Non-systematic Assessment | Fainting in reaction to blood draw. |
|
| Hypoglycemia | Endocrine disorders | Non-systematic Assessment | Hypoglycemia occurring during oral glucose tolerance test. Test prematurely stopped so that participant could ingest food. |
|
Not provided
Not provided
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Small LDL-P (nmol/L) |
|
| Total LDL-P (nmol/L) |
|
| LDL-P size (nm) |
|
| hs-CRP |
|
| Emotional (PedsQL) |
|
| Social (PedsQL) |
|
| School (PedsQL) |
|
| Psychosocial (PedsQL) |
|
| Total Score (PedsQL) |
|
| Body Esteem (IWQOL-Kids) |
|
| Social Life (IWQOL-Kids) |
|
| Family Relationships (IWQOL-Kids) |
|
| Total (IWQOL-Kids) |
|