Clinical trial NCT04270084: Metabolic Optimization Through Diet/Lifestyle Improvements For Youth
Official title: Metabolic Optimization Through Diet/Lifestyle Improvements For Youth (MODIFY)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dyslipidemias
Obesity
Keywords: cardiometabolic risk factors
lifestyle modification
visceral adiposity
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
Collaborators: name: University of California, Davis
name: NutritionQuest
First posted: 2020-02-17
Enrollment: 22
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Adolescent inclusion criteria:

Aged 10 years to 18 years Dyslipidemia (TG/HDL-c \>2.5 in non-Black males and \>2.0 in females and Black males) Central adiposity (waist to height ratio \> 0.5) Willingness to participate

Adult inclusion criteria:

Parent or adult caregiver of adolescent patient Central adiposity (waist to height ratio \>0.5) Willingness to participate

Exclusion criteria (adolescent and parent) include

* Diabetes, genetic syndrome, stage II hypertension (systolic or diastolic BP \> 95th percentile for age, sex, and height percentile + 12mm Hg or \> 140/90, whichever is lower for subjects \< 13 yr of age, \> 140/90 for all \> 13 yr of age, including PAC; history of hypertension controlled on stable medication regimen accepted)
* Medication use known to affect insulin sensitivity or lipid profiles, including metformin, statins, fibric acids or second generation atypical anti-psychotics (stable doses of stimulant or antidepressant therapy accepted)
* Current participation and unwillingness to cease activities related to a diet/exercise lifestyle modification program other than this program
* Any medical condition or syndrome with neurocognitive delay that would preclude active participation with the mobile health app
* Pregnancy or intention to become pregnant (as this will alter weight distribution)
* Inability to participate in moderate physical activity

Primary outcomes:
measure: Change in plasma ceramides
timeFrame: Change from Baseline level of plasma ceramides at 2 months
Secondary outcomes:
measure: Change in plasma lipids
timeFrame: Change from Baseline level at 2 months
measure: Change in plasma glucose
timeFrame: Change from Baseline level at 2 months
measure: Change in plasma insulin
timeFrame: Change from Baseline level at 2 months
measure: Change in plasma C-reactive protein (CRP)
timeFrame: Change from Baseline level at 2 months
measure: Change in waist circumference
timeFrame: Change from Baseline level at 2 months
measure: Change in BMI
timeFrame: Change from Baseline level at 2 months
measure: Change in physical activity
timeFrame: Change from Baseline level at 2 months
measure: Change in diet
timeFrame: Change from Baseline level at 2 months
Other outcomes:
measure: Mental health
timeFrame: Change from Baseline level at 2 months
Locations:
city: Washington
country: United States
facility: Childrens National Hospital
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Michele Mietus-Snyder, MD
role: PRINCIPAL_INVESTIGATOR
References: