Clinical trial NCT01316081: A 4-month Intervention of Antioxidant Supplementation in Overweight Children
Official title: A 4-month, Randomized, Placebo-controlled, Double-blind Intervention of Antioxidant Supplementation in Overweight Children Enrolled in an Outpatient Weight-loss Program: Effects on Oxidative and Inflammatory Markers, Hepcidin, Iron Status, and Components of the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Keywords: antioxidant supplementation
childhood obesity
hepcidin
iron status
oxidative stress
inflammation
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
First posted: 2011-03-16
Enrollment: 45
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: In obese children, low antioxidant vitamin intake and reduced antioxidant capacity are common. Weight reduction reduces subclinical inflammation in obese subjects, and, similarly, antioxidant vitamins have been shown to reduce the expression of proinflammatory cytokines. Moreover, antioxidants reduce oxidative stress which influences endothelial function and might play a crucial role in the pathogenesis of obesity-related disorders. Furthermore, overweight children and adults have a markedly increased risk for iron deficiency. The mechanism linking obesity with iron deficiency is unclear. Growing evidence suggests that the elevated inflammatory status associated with obesity increases circulating hepcidin and this contributes to iron deficiency. Weight reduction has been shown to be associated with reduced inflammation and serum hepcidin concentrations, and an improved functional iron state. Thus, reducing inflammation in obese children may improve iron metabolism and reduce their risk of iron deficiency.

Therefore, positive effects on subclinical inflammation, hepcidin/iron status and metabolic risk factors in obese children during weight loss may be enhanced by supplementation with antioxidants.

The aim of the present study is to investigate the effect of 4-month antioxidant supplementation on subclinical inflammation, hepcidin, iron status and components of the metabolic syndrome in overweight children undergoing an outpatient weight-loss program.

Our hypotheses are: 1. During an outpatient weight loss program, antioxidant supplementation will reduce oxidative and inflammatory stress associated with obesity to a greater extent than weight loss alone. 2. This will have two effects, compared to weight loss alone: a.It will reduce circulating hepcidin concentrations, and improve iron status. b.It will improve metabolic and cardiovascular risk factors.

Subjects The investigators plan to enroll 50 children who are participants in outpatient weight-loss programs in the German part of Switzerland. Enrollment will be done with the agreement and assistance of the physician supervising the weight-loss program, and the timing of the study measurements will be incorporated within the existing program schedule. It is anticipated that the baseline blood sample for this study will be obtained from the regular baseline venipuncture for the weight-loss study. Criteria for participation include age between 10 to 18 years and a BMI over the 85th percentile for age and sex. Exclusion criteria include major medical illnesses, including gastrointestinal, inflammatory, bleeding and/or endocrine disorders, a history of nephrolithiasis, unusual dietary habits (e.g. vegetarianism), major food allergies or intolerances (lactose, gluten), smoking, and use of chronic medications or vitamin/mineral antioxidant supplements.

Study design The study will be a double-blind, randomized, placebo-controlled intervention trial. Children will be randomly assigned to one of two groups: antioxidant (AO) or placebo (P) supplement. If it is necessary to enroll children from different weight-loss programs, then randomization will be stratified by program. During the 4-month weight loss period, the AO group will consume oral supplements of ascorbic acid (500mg), alpha tocopherol (400 IU), and 50 µg selenium (all from Burgerstein Vitamins, Rapperswil-Jona, Switzerland) each evening with diner, whereas the P group will consume identical-appearing placebo supplements.


Eligibility criteria: Inclusion Criteria:

* age between 10 to 18 years old
* BMI over the 85th percentile for age and sex

Exclusion Criteria:

* history of nephrolithiasis
* history of bleeding disorder
* smoking
* type 2 diabetes
* NAFLD
* Asthma

Primary outcomes:
measure: oxidative markers (isoprostanes)
timeFrame: blood sample after 4 months
measure: inflammatory parameters
timeFrame: blood sample after 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: Swiss Federal Institute of Technology , Laboratory of Human Nutrition
Study officials:
affiliation: ETH Zurich
name: Michael B Zimmermann, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murer SB, Aeberli I, Braegger CP, Gittermann M, Hersberger M, Leonard SW, Taylor AW, Traber MG, Zimmermann MB. Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents. J Nutr. 2014 Feb;144(2):193-201. doi: 10.3945/jn.113.185561. Epub 2013 Dec 18.