Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT04270084 |
Other study ID # |
Pro00010790 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
September 29, 2020 |
Est. completion date |
December 31, 2022 |
Study information
Verified date |
February 2022 |
Source |
Children's National Research Institute |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The overarching goal of this study is to evaluate plasma ceramides (Cers) as early
nutrition-sensitive biomarkers of metabolic health. The investigators will implement a diet
and lifestyle intervention to improve cardiometabolic risk factors and test the corresponding
change in Cer levels. The intervention will incorporate: a) family-level engagement,
enrolling both adolescents and one parent/adult caretaker (PAC); and b) a behavior change
mobile health (m-health) app, which will offer real-time support, education and monitoring of
diet and activity.
Description:
Dysregulated sphingolipid ceramide (Cer) metabolism impairs mitochondrial function, insulin
sensitivity and vascular reactivity and has been identified as a central common pathway
towards the dyslipidemia, central adiposity, hyperglycemia, and hypertension that define
metabolic syndrome, characterized as cardiometabolic risk (CMR). The decrease in insulin
sensitivity that occurs with age and predisposes to metabolic syndrome is preventable, a
reflection of changes in body composition rather than the aging process itself. Ectopic fat,
not fat mass per se, drives CMR, but despite mounting concern about rising prevalence of
pediatric CMR in America and globally, the use of plasma Cer as potentially mechanistic
biomarkers of ectopic fat and lipotoxicity has not been well explored. This may be driven in
part by our incomplete understanding of i) the consequences of Cer dysregulation in pediatric
CMR; ii) putative interactions between Cer and ectopic lipotoxicity; and iii) how lifestyle,
notably nutrition, impacts Cer metabolism. Information in these areas may support use of
plasma Cers as sensitive, prognostic biomarkers to guide more effective preventive lifestyle
management of aberrant weight gain and associated CMR.
In preliminary work, the investigators compared plasma sphingolipid profiles in obese
adolescents and their parent/adult caretakers (PAC). Data from this study demonstrated that
Cers (notably C:14 and C:16) are associated with dyslipidemia in both adults and youth. The
investigators also found that 2-mo of a daily nutrient bar supplementation (coupled with
weekly group counseling and exercise) significantly decreased plasma Cers more effectively
than counseling and physical exercise alone, without change in traditional biomarkers but the
extent of Cer reduction correlated with improved dyslipidemia. The investigators also found
that 10 days of dietary fructose reduction in obese pre-adolescents significantly lowers cers
in direct proportion to the clearance of ectopic hepatic adiposity.
If study hypotheses are supported, these findings will identify sensitive Cer biomarkers of
CMR with putative mechanistic insight to mitochondrial function requisite for insulin
sensitivity, metabolic flexibility, lipolysis, and weight loss, that might therefore be used
to monitor early success in lifestyle change trials.