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

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Conditions: Down Syndrome; Trisomy 21
• Enrollment: 257

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Down Syndrome	Control
Arm/Group Description	154 participants ages 10-20 years old. No intervention occurred as this is a cross-sectional observational study.	103 age-, sex-, race-, ethnicity-, and BMI percentile-matched control subjects. No intervention occurred as this is a cross-sectional observational study.
Period Title: Overall Study
Started	154	103
Completed	154	103
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Down Syndrome	Control	Total
Arm/Group Description		Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group.	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.	Total of all reporting groups
Overall Number of Baseline Participants		154	103	257
Baseline Analysis Population Description		Participants from the Down syndrome and control groups were matched on BMI percentile, age, race, ethnicity, and sex.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	154 participants	103 participants	257 participants
		14.4 (0.3)	14.7 (0.3)	14.7 (0.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	103 participants	257 participants
	Female	87 56.5%	61 59.2%	148 57.6%
	Male	67 43.5%	42 40.8%	109 42.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	103 participants	257 participants
	Hispanic or Latino	13 8.4%	6 5.8%	19 7.4%
	Not Hispanic or Latino	141 91.6%	97 94.2%	238 92.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	103 participants	257 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	3 1.9%	0 0.0%	3 1.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	30 19.5%	24 23.3%	54 21.0%
	White	117 76.0%	74 71.8%	191 74.3%
	More than one race	1 0.6%	1 1.0%	2 0.8%
	Unknown or Not Reported	3 1.9%	4 3.9%	7 2.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	154 participants	103 participants	257 participants
		154	103	257
BMI Percentile [1]; Mean (Standard Deviation); Unit of measure: Percentile
	Number Analyzed	154 participants	103 participants	257 participants
		81.4 (1.8)	79.3 (2.5)	80.5 (1.4)
		[1] Measure Description: Height & weight were measured and entered into the online CDC BMI Calculator for children and teens to determine percentile.

Outcome Measures

1. Primary Outcome

Title	Non-HDL Cholesterol
Description	Non-HDL cholesterol measured via fasting blood draw
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	147	103
Median (Inter-Quartile Range); Unit of Measure: mg/dl
	128; (104 to 153)	107; (92 to 123)

2. Primary Outcome

Title	Lipid Subparticles
Description	Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0.

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	147	103
Median (Inter-Quartile Range); Unit of Measure: nmol/L
Small HDL-P (nmol/L)	9.8; (5.3 to 14)	11.7; (8.9 to 14.9)
Large VLDL-P (nmol/L)	3.9; (2.3 to 5.7)	2.4; (1.5 to 4.1)
Small LDL-P (nmol/L)	518; (401 to 639)	420; (315 to 529)
Total LDL-P (nmol/L)	977; (806 to 1193)	850; (693 to 997)

3. Primary Outcome

Title	Lipid Subparticles (Size)
Description	Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants excluded from lipid analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0.

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	147	103
Median (Inter-Quartile Range); Unit of Measure: nm
HDL-P size (nm)	9.6; (9.2 to 9.9)	9.6; (9.1 to 9.9)
VLDL-P size (nm)	49.2; (45.8 to 53.6)	47.1; (44.2 to 50.7)
LDL-P size (nm)	20.7; (20.3 to 21.2)	20.7; (20.2 to 21.1)

4. Primary Outcome

Title	Insulin Resistance
Description	Insulin Resistance (HOMA-IR) was calculated as [fasting insulin (uIU/mL) x fasting glycemia (mmol/L)]/22.5
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants excluded from insulin resistance analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=147, Controls=103.

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	147	103
Median (Inter-Quartile Range); Unit of Measure: HOMA-IR
	1.8; (1.0 to 2.7)	1.95; (0.92 to 3.4)

5. Primary Outcome

Title	Cardiometabolic Risk Biomarker Proteins
Description	hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants excluded from analysis if they failed to complete blood draw or were diagnosed with Type 1 Diabetes: DS=7, Controls=0.

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	147	103
Median (Inter-Quartile Range); Unit of Measure: ng/dL
IL-6	2.3; (1.4 to 3.5)	1.5; (1.4 to 2.9)
PAI-1	0.0204; (0.0132 to 0.0327)	0.0254; (0.0147 to 0.0385)
hs-CRP	2.5; (0.64 to 6.9)	1.0; (0.32 to 4.5)

6. Primary Outcome

Title	Abnormal Glucose Tolerance
Description	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.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

Participants completed an oral glucose tolerance test if they were in the overweight or obese categories: DS n=96, Control n=64.

Arm/Group Title	Down Syndrome (Overweight & Obese Only)	Control (Overweight Obese Only)
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	96	64
Measure Type: Count of Participants; Unit of Measure: Participants
Impaired Fasting Glucose	12 12.5%	3 4.7%
Abnormal Glucose Tolerance	10 10.4%	3 4.7%

7. Primary Outcome

Title	Visceral Fat
Description	Adiposity measured by Dual-energy X-ray absorptiometry
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	154	103
Median (Inter-Quartile Range); Unit of Measure: cm^2
	54.5; (39.9 to 81.9)	55.9; (40.6 to 95.3)

8. Primary Outcome

Title	Body Mass Measures
Description	Adiposity measured by Dual-energy X-ray absorptiometry
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	154	103
Median (Inter-Quartile Range); Unit of Measure: g
Whole Body Fat Mass	18607.5; (12034.8 to 27557.7)	22372.1; (16143 to 39723.8)
Whole Body Lean Mass	34927.16; (27527.39 to 42383.86)	44108.3; (32439.9 to 52181.3)

9. Primary Outcome

Title	Left Ventricular Mass
Description	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.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

LVM was available in 136 adolescents with DS (60M/76F) and 101nonDS controls (41M/60F).

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	136	101
Median (Inter-Quartile Range); Unit of Measure: g
	68.3; (32.1 to 135)	64; (53 to 77)

10. Primary Outcome

Title	Pulse Wave Velocity
Description	Cardiac end organ injury assessed by Pulse Wave Velocity (PWV)
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

PWV was available in 129 adolescents with DS and 97 controls

Arm/Group Title	Down Syndrome	Control
Arm/Group Description:	Down syndrome participants in observational study.	Control participants in observational study.
Overall Number of Participants Analyzed	129	97
Median (Inter-Quartile Range); Unit of Measure: m/s
	5; (4.5 to 5.6)	4.9; (4.5 to 5.5)

11. Secondary Outcome

Title	Health Related Quality of Life - PedsQL
Description	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.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Down Syndrome, Obese	Down Syndrome, Not Obese	Control, Obese	Control, Not Obese
Arm/Group Description:	For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group. For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	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. For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.
Overall Number of Participants Analyzed	63	87	24	34
Mean (Standard Deviation); Unit of Measure: score on a scale
Physical Functioning (PedsQL)	68.3 (18.5)	73.2 (21.4)	78.9 (18.8)	89.7 (19.7)
Emotional (PedsQL)	73.3 (76.0)	76.0 (14.9)	75.6 (19.5)	77.2 (25.1)
Social (PedsQL)	60.7 (20.9)	63.3 (19.2)	80.4 (16.4)	85.0 (22.3)
School (PedsQL)	65.1 (18.2)	64.0 (17.2)	75.6 (18.5)	80.0 (24.0)
Psychosocial (PedsQL)	65.1 (14.3)	67.8 (13.8)	77.2 (15.4)	80.7 (22.4)
Total Score (PedsQL)	66.2 (13.2)	69.6 (14.2)	77.8 (14.0)	83.9 (21.0)

12. Secondary Outcome

Title	Health Related Quality of Life - IWQOL
Description	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.
Time Frame	Study Visit 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Down Syndrome, Obese	Down Syndrome, Not Obese	Control, Obese	Control, Not Obese
Arm/Group Description:	For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group. For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.	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. For the Psychosocial risk factors secondary analysis Down Syndrome and Control Groups were further divided into Obese and Not Obese sub groups for analysis.
Overall Number of Participants Analyzed	63	87	24	34
Mean (Standard Deviation); Unit of Measure: score on a scale
Physical Comfort (IWQOL-Kids)	83.3 (18.6)	97.1 (7.5)	86.0 (16.6)	98.2 (7.9)
Body Esteem (IWQOL-Kids)	91.4 (11.1)	98.0 (5.4)	73.9 (25.7)	93.9 (12.8)
Social Life (IWQOL-Kids)	89.7 (17.6)	98.4 (5.9)	80.7 (21.0)	95.0 (14.0)
Family Relationships (IWQOL-Kids)	93.8 (13.5)	98.6 (5.3)	93.2 (11.2)	97.5 (8.9)
Total (IWQOL-Kids)	89.8 (11.7)	98.0 (5.1)	82.4 (16.7)	95.9 (10.5)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Down Syndrome		Control
Arm/Group Description	Our goal is to enroll 155 subjects with Down syndrome, and to compare their data to our control group.		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.
All-Cause Mortality
	Down Syndrome		Control
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/154 (0.00%)		0/103 (0.00%)
Serious Adverse Events
	Down Syndrome		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/154 (0.00%)		0/103 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Down Syndrome		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/154 (4.55%)		3/103 (2.91%)
Endocrine disorders
Hypoglycemia * [1]	1/154 (0.65%)	1	0/103 (0.00%)	0
Gastrointestinal disorders
Vomiting * [2]	1/154 (0.65%)	1	0/103 (0.00%)	0
General disorders
Fainting * [3]	0/154 (0.00%)	0	1/103 (0.97%)	1
Skin and subcutaneous tissue disorders
Skin irritation * [4]	5/154 (3.25%)	5	2/103 (1.94%)	2
* Indicates events were collected by non-systematic assessment; [1] Hypoglycemia occurring during oral glucose tolerance test. Test prematurely stopped so that participant could ingest food.; [2] Vomiting in reaction to glucola ingestion associated with oral glucose tolerance test.; [3] Fainting in reaction to blood draw.; [4] Skin irritation due to physical activity armband wear. If irritation occurred armband wear was discontinued.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Andrea Kelly
• Organization: The Children's Hopsital of Philadelphia
• Phone: 215590-3174
• EMail: kellya@email.chop.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT01821300
• Other Study ID Numbers: 12-009233; 1R01HD071981-01A1 ( U.S. NIH Grant/Contract )
• First Submitted: March 27, 2013
• First Posted: April 1, 2013
• Results First Submitted: October 31, 2018
• Results First Posted: January 9, 2019
• Last Update Posted: July 31, 2019