Down SyndromeNCT01821300

Down Syndrome Metabolic Health Study

An observational study of Down Syndrome and Trisomy 21, run by Children's Hospital of Philadelphia at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 10 to 20 yearsHealthy volunteers can take part
Conditions the study is for: Down Syndrome, Trisomy 21
How many people: 257 participants
Where: 2 sitesUnited States
Study dates: Feb 2013to 25 Aug 2017
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 10 to 20 years
All sexes
Healthy volunteers accepted
Child, Adult

Study population: Participants will be recruited from primary care and speciality clinics, Trisomy 21 events, T21 interest groups, and referrals.

Who may be able to join

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

Who cannot join

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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's National Medical Center
Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: Cardiometabolic Risk and Obesity in Adolescents With Down Syndrome

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.

Read the 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.

Conditions: Down Syndrome, Trisomy 21
Keywords: Down syndrome, Philadelphia, The Children's Hospital of Philadelphia, Body composition, Obesity, Cardiovascular
Medical subject headings: Down Syndrome, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01821300
Study group	Role	What they receive
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Non-HDL Cholesterol
Non-HDL cholesterol measured via fasting blood draw
Measured: Study Visit 1
Lipid Subparticles
Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Measured: Study Visit 1
Lipid Subparticles (Size)
Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Measured: Study Visit 1
Insulin Resistance
Insulin Resistance (HOMA-IR) was calculated as [fasting insulin (uIU/mL) x fasting glycemia (mmol/L)]/22.5
Measured: Study Visit 1
Cardiometabolic Risk Biomarker Proteins
hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1.
Measured: 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.
Measured: Study Visit 1
Visceral Fat
Adiposity measured by Dual-energy X-ray absorptiometry
Measured: Study Visit 1
Body Mass Measures
Adiposity measured by Dual-energy X-ray absorptiometry
Measured: 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.
Measured: Study Visit 1
Pulse Wave Velocity
Cardiac end organ injury assessed by Pulse Wave Velocity (PWV)
Measured: Study Visit 1

Secondary outcomes (2)

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.
Measured: 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.
Measured: Study Visit 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 201325 Aug 2017

First posted1 Apr 2013 (estimated)
Study startFeb 2013
Primary completion25 Aug 2017
Study completion25 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Down SyndromeStudies of the same condition, open and under way.
More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Cross-sectional
Enrolment: 257 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01821300
Sponsor's protocol ID: 12-009233
Other IDs: 1R01HD071981-01A1
Status last verified: Jul 2019
First submitted: 27 Mar 2013
Last updated: 31 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

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.
PubMed 31315916
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.
PubMed 31201031
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.
PubMed 30386863
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.
PubMed 28751125

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Down Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cardiometabolic Risk and Obesity in Adolescents With Down Syndrome
ClinicalTrials.gov ID: NCT01821300
Acronym / sponsor ID: 12-009233
Conditions: Down Syndrome, Trisomy 21
Keywords: Down syndrome, Philadelphia, The Children's Hospital of Philadelphia, Body composition, Obesity, Cardiovascular
Study type: Observational
Recruitment status: Completed
Enrolment: 257 participants (actual)
Lead sponsor: Children's Hospital of PhiladelphiaUniversity, hospital or other
Collaborators: National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Feb 2013
Primary completion: 25 Aug 2017 (actual)
Study completion: 25 Aug 2017 (actual)
First posted: 1 Apr 2013 (estimated)
Results: Posted 9 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Observational model: Case-control
Time perspective: Cross-sectional
Number of arms: 2

Arm	Type	Receives
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.

Who may qualify

Ages: 10 to 20 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult
Study population: Participants will be recruited from primary care and speciality clinics, Trisomy 21 events, T21 interest groups, and referrals.

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

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)

2 secondary outcomes

Health Related Quality of Life - PedsQL
Time frame: Study Visit 1
Health Related Quality of Life - IWQOL
Time frame: Study Visit 1

Results and safety

Results posted to the registry on 9 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Down Syndrome	154	154
Control	103	103

Primary outcome: Non-HDL Cholesterol

Time frame: Study Visit 1. Median (Inter-Quartile Range). Unit: mg/dl

Measure	Down Syndrome n = 147	Control n = 103
Value	128 (104 to 153)	107 (92 to 123)

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

Primary outcome: Lipid Subparticles

Time frame: Study Visit 1. Median (Inter-Quartile Range). Unit: nmol/L

Measure	Down Syndrome n = 147	Control n = 103
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)

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

Primary outcome: Lipid Subparticles (Size)

Time frame: Study Visit 1. Median (Inter-Quartile Range). Unit: nm

Measure	Down Syndrome n = 147	Control n = 103
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)

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

Primary outcome: Insulin Resistance

Time frame: Study Visit 1. Median (Inter-Quartile Range). Unit: HOMA-IR

Measure	Down Syndrome n = 147	Control n = 103
Value	1.8 (1.0 to 2.7)	1.95 (0.92 to 3.4)

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

2 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Down Syndrome	0 of 154 (0%)	7 of 154 (4.5%)	0 of 154
Control	0 of 103 (0%)	3 of 103 (2.9%)	0 of 103

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31315916Magge 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.
Derived from this study: PubMed 31201031Kelly 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.
Derived from this study: PubMed 30386863Kelly 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.
Derived from this study: PubMed 28751125Xanthopoulos 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.
Individual participant dataSharing planned: No

Related trials for Down Syndrome

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrea Kelly, MD, MSCE principal investigator

Children's Hospital of Philadelphia

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Down Syndrome and Trisomy 21, run by Children's Hospital of Philadelphia at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Non-HDL Cholesterol (time frame: Study Visit 1). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01821300, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2019; AzTrials last refreshed its copy on 31 Oct 2026.