Clinical trial NCT04112251: Effects of COcoa Supplement in OBese Adolescent Subjects
Official title: Effect of Cocoa Flavonols Oral Supplement on Body Composition, Metabolic, Inflammatory and Oxidative Profile in Obese Subject 10 to 16 Years
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Childhood Obesity
Adolescent Obesity
Keywords: Childhood Obesity
Cocoa Flavanols
Adolescent Obesity
Lead sponsor: National Polytechnic Institute, Mexico
Sponsor class: OTHER
Collaborators: name: Hospital Infantil de Mexico Federico Gomez
name: Instituto Nacional de Salud Publica, Mexico
name: Universidad Nacional Autonoma de Mexico
First posted: 2019-10-02
Enrollment: 116
Sex: ALL
Minimum age (years): 10
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled clinical trial will be conducted, which will be conducted at the Federico Gómez Children's Hospital in Mexico, during the period from October 2019 to October 2020; with patients with exogenous obesity from 10 to 16 years.
Primary purpose: TREATMENT

Brief summary: Childhood obesity is a serious public health problem internationally. In addition to being associated with the early onset of chronic degenerative diseases such as diabetes, dyslipidemias, coronary artery diseases, among others.

Changes in lifestyle habits are the main axis in the treatment of this disease; however, low adherence to these changes are reflected in the increase in their incidence and prevalence.

There is diverse evidence that the use of flavonoids from cocoa such as (-) - epicatechin are able to prevent cardiovascular risks, decrease insulin resistance, mean arterial pressure, control the lipid profile; mediate oxidative stress, improve mitochondrial function and regulate the inflammatory process in patients with heart failure and diabetes mellitus. Therefore, our working hypothesis is the administration of the oral supplement of flavonoids from cocoa for 12 weeks will be able to reduce the percentage of body fat, improve the metabolic profile and regulate inflammatory and oxidative processes in obese patients 10-16 years, compared to those patients who only take a usual therapy consisting of recommendations of healthy diet and physical activity.

For this, a randomized, double-blind, placebo-controlled clinical trial will be carried out, which will be carried out at the Federico Gómez Children's Hospital of Mexico, during the period from October 2019 to October 2020; with obese patients from 10 to 16 years distributed homogeneously at random in two groups: the control group (Placebo) and the intervention group (Flavonoids from cocoa) both groups affected for 12 weeks.

The variables studied will be: percentage of muscle mass, percentage of fat, body mass index (BMI), waist circumference (CC), fasting glucose, fasting insulin, lipid profile (Total cholesterol, Triglycerides, HDL-c, LDL -c, Ratio TG / HDL-c, High Sensitivity C-Reactive Protein (HS-CRP), Interleukins (IL-6, IL-10), Tumor Growth Factor beta (TGF-β) and Tumoral Necrosis Factor alpha (TNF-α), carbonylated proteins, Malondialdehyde (MDA), indirect calorimetry by respiratory coefficient and treatment adherence.

Detailed description: Childhood obesity is global health problem, due to the constant increase in its incidence and prevalence. Having this disease helps increase the costs of care for Chronic Noncommunicable Diseases. The increase in its prevalence since 1975 from 1% to 6% (girls) and 8% (boys) in 2016 between the ranges of 5 to 19 years.

Mexico, occupies the first place worldwide in childhood obesity, only by data from National Health and Nutrition Survey 2016 , it is considered that approximately 3 out of 10 children, 4 out of 10 adolescents present this health problem; the population with the highest health risk being ages between 10 and 17 years. In 2016, the prevalence of obesity in the population between 5 and 11 years old was 15.3% and in adolescents between 12 and 19 years old it was 13.9% .

Although, the scientific evidence has focused on studying different strategies for the prevention, control and treatment of childhood obesity complications; The prevalence of this has not yet been reduced or controlled favorably. It has been demonstrated through meta-analysis and randomized clinical trials that the use of flavonoids from cocoa, such as epicatechin at a concentration of 50 mg to 100 mg / day for 6 to 18 weeks, may decrease the risk of cardiovascular and metabolic diseases, Because it reduces: insulin resistance, diastolic blood pressure, triglycerides, LDL-c and increased HDL-c. These biological effects are related to the antioxidant capacity (inhibition of Nicotinamide adenine dinucleotide phosphate oxidase (NAHPH) and increase of endothelial Nitric Oxide Synthase (eNOS), protein interaction and cell signaling that these compounds have (inhibition of Tumoral Necrosis Factor alpha (TNF-α) and Necrosis Factor beta (NF-β); MAPK pathway regulation ) and finally by the regulation of the inflammatory process through the modulation of the pro-inflammatory elements (Decrease of Il-6, TNF-α and PCR-HS), so it is attractive to establish it as an alternative treatment to reduce the risk of generate comorbidities This research aims to solve the following question: What is the effect of oral supplementation of flavonoids from cocoa on body composition, metabolic, inflammatory and oxidative profile in obese patients 10-16 years old?

This work aims to demonstrate the effect of oral supplementation of flavonoids from cocoa on body composition, anthropometric parameters, biochemical, inflammatory and oxidative markers in obese patients in order to reduce the risk of suffering from other comorbidities, such as metabolic syndrome. , diabetes, high blood pressure and cardiovascular diseases.

From this study the investigators can know the effectiveness of the use of flavonoids from cocoa as epicatechin in a child population and demonstrate the regulatory effect of epicatechin on lipids, inflammation and oxidation. The results obtained from this research will provide us with the necessary evidence to propose whether the use of these flavonoids to prevent the occurrence of other comorbidities of childhood obesity.

Material and methods:

Type of study and universe: A randomized, double-blind, placebo-controlled clinical trial will be conducted, which will be conducted at the Federico Gómez Children's Hospital in Mexico, during the period from October 2019 to October 2020; with patients with exogenous obesity from 10 to 16 years.

Sample size:

It was calculated by the G \* Power software version 3.1, considering an alpha error of 0.05, a power of 95% and a minimum expected difference between groups: control and intervention based on the variables of interest according to the reports of Other studies. Assuming that the sample size with the largest number of subjects (n = 40 subjects) is sufficient to find significant differences in all the variables of interest. Once the minimum necessary sample size (40 subjects per group) for the research protocol has been calculated, the sample adjustment for losses of 30% will be made, with a total of 116 research subjects (58 for each group).

Description of the intervention:

Phase 1. Generation of healthy habits: In order to standardize patients to establish greater control in the recommendations of diet and physical activity, the implementation of educational workshops 4 weeks before the start of the intervention was considered. The content of the recommendations workshops for a healthy diet and physical activity is based on the recommendations issued by World Health Organization (WHO), Official Mexican Standard of the Ministry of Health (NOM-043-SSA2-2012) and the Guidelines for diabetes prevention programs.

Phase 2. Evaluation of the intervention: Once the phase of standardization of healthy habits is finished, the evaluation of the intervention will begin after the randomization of the study population, in 2 groups: Control Group (Placebo) that will receive the usual therapy of the endocrinology service, dietary recommendations, physical activity recommendations and the administration of one oral capsule of the placebo every 12 hours for 12 weeks and the Experimental group (Supplement of flavonoids from cocoa the participants will receive the usual therapy of the endocrinology service, dietary recommendations, physical activity recommendations and the administration of one capsule every 12 hours for 12 weeks.

Randomization of the sample:

For the selection of intervention and control groups, select a randomized selection of research subjects through the online Research Randomizer (www.randomizer.org) taking into account 2 unique sets, with 60 numbers per-set, a range between 1 and 120.

Blinding of the intervention:

For this study, a double blinding was established and masking techniques will be established to avoid the identification of the intervention. Blinding will only be opened when required by the research ethics committee or secretary of health, or when the patient presents a serious adverse event; same that will be informed before the competent authorities.

This work will be guided by the ethical principles for research in humans of the Helsinki Declaration 2013 and the recommendations postulated in the guide of good clinical practices issued by the WHO. In accordance with the provisions of the Regulations of the General Law on Research Health in Article 17, it is classified as a risk greater than the minimum. Currently, it has the approval of the Biosafety Committees, the Research and Research Ethics Committees of the Federico Gómez Children's Hospital of Mexico (HIM-2018-100).

Statistical analysis plan:

The data obtained from the results of this research will be subjected to an analysis by protocol and by intention to be treated. For the statistical analysis of the results, the Statistical Package for the Social Sciences Softaware by International Business Machines (IBM SPSS) version 24 program will be used. Reporting the mean and standard deviation for the quantitative variables; median and range for qualitative variables. The distribution of the sample studied will be carried out the normality test of Kolmogórov-Smirnov. For the evaluation of the changes of the variables of interest, in case of presenting a normal distribution, repeated measures ANOVA and T Student will be used for related samples. In case of presenting a free distribution will be used will be the Kruskal - Wallis and Wilcoxon tests. Finally, to evaluate the presence of changes between the groups through the covariance analysis of the deltas of change of the variables studied.

Eligibility criteria: Inclusion Criteria:

* Patients 10 to 16 years old.
* Patients who do not take any pharmacological treatment for chronic conditions.
* Have the signed informed consent and assent.
* Only the participation of one research subject per family will be accepted.

Exclusion Criteria:

* Carrying diseases that can alter body weight (endocrine, hematological, immunological, neurological, psychiatric, genetic alterations).
* Presence of mental retardation and other chronic diseases.
* That they receive medications that can affect weight, lipid and carbohydrate metabolism.
* That you are actively participating in some other research protocol.
* Do not have a body limb.

Primary outcomes:
measure: TG / HDL-C ratio
timeFrame: 3 month
measure: Body Fat Mass (BFM) percentage
timeFrame: 3 month
measure: Insulin Resistance Homeostasis Evaluation Model (HOMA-IR)
timeFrame: 3 month
Secondary outcomes:
measure: Quantitative determination of HS-PCR, TNF-α, TFG-β, IL-6 and IL-10
timeFrame: 3 month
measure: Determined by the quantification of carbonylated protein
timeFrame: 3 month
measure: Determined by the quantification of Malondialdehyde (MDA)
timeFrame: 3 month
measure: Body Mass Index (BMI)
timeFrame: 1 Month
measure: Indirect Calorimetry
timeFrame: 3 month
Other outcomes:
Locations:
Study officials:
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