Role of Microbiota, Inflammation and Oxidative Stress in the Pathophysiology of Obesity: Therapeutic Potential of Citrus Flavonoids
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- To evaluate insulin resistance index
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •patients with a BMI of 30 -40 kg/m2, between 18 and 65 years of age.
- •Obesity of more than five years' duration
- •Patients will maintain a stable weight (±2 kg) during the 3 months prior to the study.
排除标准
- •Patients with acute or chronic inflammatory diseases and established liver and kidney failure (based on transaminase levels ±2 SD of the mean and estimated glomerular filtration rate using the CKD-EPI formula >60), neoplastic diseases and secondary causes of obesity (hypothyroidism, Cushing's syndrome), use of drugs that may influence inflammatory status or insulin sensitivity (NSAIDs, corticosteroids, anti-TNFα), treatment with insulin or GLP1 inhibitors, type 1 diabetes, morbid obesity (BMI>40 kg/m2), hypertriglyceridaemia (> 400 mg/dl), fructose intolerance.
结局指标
主要结局
To evaluate insulin resistance index
时间窗: 5 years
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).
Analyze the significant differences between metabolomic profile before and after the dietetic intervention, and between both groups (flavonoid-enriched juice vs placebo)..
时间窗: 5 years
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.
次要结局
- Assess significant changes in body fat mass percentage after the dietetic intervention.(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.(5 years)
- To evaluate the composition and diversity of gut microbiota(5 years)
- To identify serum biomarkers using a metabolomic approach(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.(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.(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.(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.(5 years)
- Assess significant changes in C3 protein after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.(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.(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.(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.(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.(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.(5 years)
- Evaluate significant changes in ROS levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.(5 years)
- Assess significant improvements in glutathione levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.(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.(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.(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.(5 years)
研究者
Celia Bañuls
Principal Investigator
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana