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| Name | Class |
|---|---|
| Instituto de Salud Carlos III | OTHER_GOV |
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The aim of this study is to evaluate whether the intake of a functional juice enriched in citrus polymethoxylated flavonoids is able to improve the glycaemic profile and insulin resistance of obese patients by reversing the associated oxidative and inflammatory stress, as well as the differential alteration of the intestinal microbiota. To achieve this, a prospective, randomised, double-blind, placebo- controlled, clinical-baseline intervention study will be conducted in obese patients (BMI=30-40 kg/m2) with type 2 diabetes (DM2) (n=40) and obese patients without alterations in carbohydrate metabolism (n=40). Each of these groups will be randomly divided into 2 subgroups (n=20), one of which will receive polymethoxyflavonoid-enriched orange juice (14%: nobiletin, sinensetin, tangeretin) (200 ml/ day) and the other group will receive the corresponding placebo juice for 8 weeks. In addition, all of them will receive a hypocaloric diet. Anthropometric parameters, body composition and nutritional status will be assessed, cardiovascular risk factors and comorbidities will be studied (HT, SAHS, dyslipidaemia, insulin resistance), oxidative stress parameters will be compared (total and mitochondrial ROS production, mitochondrial membrane potential, glutathione levels by static cytometry and mitochondrial respiration rate by Seahorse flow analyser), antioxidant enzymes (SOD, GPx) and molecular oxidation products (Carbonyl proteins and 8-oxo-dG, LDLox) and LPS by ELISA techniques, inflammatory parameters (IL6, TNFa, IL1b, adiponectin, PAI-1, IL10) by Luminex XMAP technology in serum. Metabolomic analysis will also be performed in plasma (NMR spectroscopy and PLS-DA), and the content and diversity of the gut microbiota (16S rRNA amplicons, and direct metagenomic sequencing, with Illumina MiSeq technology) will be assessed in faeces, before and after the dietary intervention. Individualised dietary follow-up and assessment of subjects' quality of life will be carried out.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Flavonoid-enriched juice and low-calorie diet for obese patients | Active Comparator | Subjects will receive nutritional intervention by a registered dietician and a flavonoid-enriched juice supplement for 8 weeks. The dietary intervention consists of healthy dietary recommendations and hypocaloric diet if necessary (overweight, obesity). |
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| Pacebo juice and low-calorie diet for obese patients | Placebo Comparator | Subjects will receive nutritional intervention by a registered dietitian and a placebo in the form of juice for 8 weeks. The dietary intervention consists of healthy dietary recommendations and hypocaloric diet if necessary (overweight, obesity). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Flavonoid-enriched juice and a low-calorie diet | Dietary Supplement | Orange juice enriched in flavonoids (14%: nobiletin, sinensetin, tangeretin) (200 ml/day) and low calorie diet |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate insulin resistance index | Evaluate if there is an improvement in insulin resistance levels after the intervention depending on the intake of a flavonoid-enriched juice or its corresponding placebo for 6 weeks, in obese patients without alterations in carbohydrate metabolism and obese patients with type 2 diabetes (DM2). HOMA-IR will be used. Participants will be considered to have achieved an improvement in insulin resistance levels if they normalize its value (normality values defined between 0 and 3.8 units). | 5 years |
| Analyze the significant differences between metabolomic profile before and after the dietetic intervention, and between both groups (flavonoid-enriched juice vs placebo).. | NMR spectra will be used to obtain spectra from serum samples from the cohort. In order to evaluate if there will be significant differences after the dietetic intervention, a PLS-DA model for discrimination between basal and post intervention levels will be performed. Scores plots will be calculated with a 95% confidence interval. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assess significant changes in body fat mass percentage after the dietetic intervention. | Percentage of body fat mass will be measured by bioelectrical impedance. It is considered to be high when ≥25% in men and ≥30% in women. A significant improvement will be considered when notable differences are observed in the mean values between groups (flavonoid-enriched juice vs. placebo) measured through p-value (<0.05) with a 95% confidence interval. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FISABIO | Valencia | Valencia | 46020 | Spain |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007249 | Inflammation |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Food supplement: placebo juice and a low calorie diet | Dietary Supplement | Placebo juice (200 ml/day) and a low calorie diet |
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| 5 years |
| To assess significant changes in triglycerides before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients. | Participants will be considered to have achieved an improvement in plasmatic triglycerides level if they normalize its value (normality values defined between 0 and 150mg/dL). | 5 years |
| To evaluate the composition and diversity of gut microbiota | To evaluate the diversity of gut microbiota in faeces (measured by alpha-diversity) before and after the use of a flavonoid-enriched juice and its placebo in the same groups of patients. To asses the differences in alpha-diversity of the intestinal microbiota in both groups, it will be evaluated whether there are significant differences between the Shannon indices of the two groups. The results are interpreted as follows: values less than 2 are considered low in diversity and values greater than 3 are high in species diversity. | 5 years |
| To identify serum biomarkers using a metabolomic approach | To identify serum biomarkers using a metabolomic approach before and after intervention with flavonoid-enriched juice or placebo in the same groups of patients. NMR spectra will be used to obtain spectra from serum samples from the cohort. In order to evaluate if there will be significant differences after the dietetic intervention (according to the flavonoid-enriched juice or placebo intake), a PLS-DA model for discrimination between basal and post intervention levels will be performed. Scores plots will be calculated with a 95% confidence interval. | 5 years |
| Evaluate significant changes in % of weight loss after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| To assess significant changes in LDLc before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients. | Participants will be considered to have achieved an improvement in serum cLDL levels if they normalize its value (normality values defined between 0 and 130mg/dL). | 5 years |
| To assess significant changes in HDLc before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients. | Participants will be considered to have achieved an improvement in serum cHDL levels if they normalize its value (normality values defined between 45 and 70mg/dL in women, and 40 to 70mg/dL in men). | 5 years |
| Evaluate significant changes in high-sensitivity C-reactive protein (hs-CRP) after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Participants will be considered to have achieved an improvement in high-sensitivity C-reactive protein levels if they normalize its value (normality values defined between 0 and 1.69mg/dl). | 5 years |
| Assess significant changes in C3 protein after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Participants will be considered to have achieved an improvement in C3 protein if they normalize its value (normality values defined between 81 and 157mg/dl). | 5 years |
| Evaluate significant changes in plasmatic homocysteine as a inflammatory parameter after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Participants will be considered to have achieved an improvement in plasmatic homocysteine if they normalize its value (normality values defined between 5 and 15µmol/L). | 5 years |
| Assess significant changes in interleukin 1-beta (IL-1B) levels as a pro-inflammatory molecule after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | IL-1B levels will be measured using the Luminex® 200 analyzer system. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Evaluate significant changes in interleukin 6 (IL-6) levels as a pro-inflammatory molecule after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | IL-6 levels will be measured using the Luminex® 200 analyzer system. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Assess significant changes in tumor necrosis factor alpha (TNF-alpha) levels as a pro-inflammatory molecule after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | TNF-alpha levels will be measured using the Luminex® 200 analyzer system. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Evaluate significant changes in superoxide dismutase (SOD) levels as a pro-inflammatory molecule after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Superoxide dismutase levels will be measured using the Luminex® 200 analyzer system. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Evaluate significant changes in ROS levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Total ROS levels will be assessed by a flow cytometry assay. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Assess significant improvements in glutathione levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Total glutathione levels will be assessed by a flow cytometry assay. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Assess significant improvements in total free radicals and superoxide levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Total free radicals and superoxide content will be assessed by a flow cytometry assay. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Evaluate significant improvements in mitochondrial ROS production after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Mitochondrial ROS production will be assessed by a flow cytometry assay. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| Analyze significant improvements in mitochondrial membrane potential after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention. | Mitochondrial membrane potential will be assessed by a flow cytometry assay in PBMCs. A significant improvement will be considered when notable differences are observed in the mean values between groups measured through p-value (<0.05) with a 95% confidence interval. | 5 years |
| D004700 | Endocrine System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |