Metabolic Optimization Through Diet/Lifestyle Improvements For Youth

Overview

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.

Full Title of Study: “Metabolic Optimization Through Diet/Lifestyle Improvements For Youth (MODIFY)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2020

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.

Interventions

  • Behavioral: Alive-Family
    • All participants receive lifestyle modification through use of m-health app

Arms, Groups and Cohorts

  • Other: Treatment
    • Participants will be asked use a mobile health (m-health) app for 2 months. The app is designed to provide weekly education and motivation about healthful diet and physical activity behaviors in adolescents and their parent/adult caretaker. Both adolescent and parent/adult caretaker participants will use the app to enter weekly self-report data, set healthy eating and exercise goals, and receive educational and motivational content. Participants will conduct a weekly self-assessment of waist circumference, diet, and physical activity during the 2 month trial.

Clinical Trial Outcome Measures

Primary Measures

  • Change in plasma ceramides
    • Time Frame: Change from Baseline level of plasma ceramides at 2 months
    • S1P, C:14, and C:16

Secondary Measures

  • Change in plasma lipids
    • Time Frame: Change from Baseline level at 2 months
    • Plasma triglycerides, HDL-c, LDL-c
  • Change in plasma glucose
    • Time Frame: Change from Baseline level at 2 months
  • Change in plasma insulin
    • Time Frame: Change from Baseline level at 2 months
  • Change in plasma C-reactive protein (CRP)
    • Time Frame: Change from Baseline level at 2 months
  • Change in waist circumference
    • Time Frame: Change from Baseline level at 2 months
  • Change in BMI
    • Time Frame: Change from Baseline level at 2 months
    • weight for height (Kg/M^2)
  • Change in physical activity
    • Time Frame: Change from Baseline level at 2 months
    • Physical activity is assessed by self-report questionnaire. The activity questionnaire asks about frequency and duration of performance of a list of activities.
  • Change in diet
    • Time Frame: Change from Baseline level at 2 months
    • Diet assessment by food frequency questionnaire (FFQ) to determine quantity and quality of macronutrients (carbs, protein, fat) and food groups (i.e. sugar sweetened beverages, fruits, vegetables, etc.) indexed as healthy eating score (Alternative Healthy Eating Index) on a scale of 2.5 to 87.5 with a higher score reflecting a more healthful diet.

Participating in This Clinical Trial

Adolescent inclusion criteria:

Aged 12 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

Gender Eligibility: All

Minimum Age: 11 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Children’s National Research Institute
  • Collaborator
    • University of California, Davis
  • Provider of Information About this Clinical Study
    • Principal Investigator: Michele Mietus-Snyder, Associate Professor – Children’s National Research Institute
  • Overall Official(s)
    • Michele Mietus-Snyder, MD, Principal Investigator, Children’s National Research Institute
  • Overall Contact(s)
    • Michele Mietus-Snyder, MD, 202-476-5161, MMSnyder@childrensnational.org

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