Metabolic Optimization Through Diet/Lifestyle Improvements For Youth

Obesity Clinical Trial

— MODIFY  

Official title:

Metabolic Optimization Through Diet/Lifestyle Improvements For Youth (MODIFY)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04270084
• Other study ID #: Pro00010790
• Status: Active, not recruiting
• Phase: N/A
• 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
• 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: December 31, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyslipidemias
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	Childrens National Hospital	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Children's National Research Institute	NutritionQuest, University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mental health	Mood and outlook will be assessed by self-report questionnaire: Patient Health Questionnaire for somatic symptoms, anxiety, and depression (PHQ-SADS) a continuous scale (0-86) with higher scores reflecting poorer mental health.	Change from Baseline level at 2 months
Primary	Change in plasma ceramides	S1P, C:14, and C:16	Change from Baseline level of plasma ceramides at 2 months
Secondary	Change in plasma lipids	Plasma triglycerides, HDL-c, LDL-c	Change from Baseline level at 2 months
Secondary	Change in plasma glucose		Change from Baseline level at 2 months
Secondary	Change in plasma insulin		Change from Baseline level at 2 months
Secondary	Change in plasma C-reactive protein (CRP)		Change from Baseline level at 2 months
Secondary	Change in waist circumference		Change from Baseline level at 2 months
Secondary	Change in BMI	weight for height (Kg/M^2)	Change from Baseline level at 2 months
Secondary	Change in physical activity	Physical activity is assessed by self-report questionnaire. The activity questionnaire asks about frequency and duration of performance of a list of activities.	Change from Baseline level at 2 months
Secondary	Change in diet	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.	Change from Baseline level at 2 months