Clinical trial NCT06680635: Effect of Citrus Flavonoids on Obesity.
Official title: Role of Microbiota, Inflammation and Oxidative Stress in the Pathophysiology of Obesity: Therapeutic Potential of Citrus Flavonoids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity Adult Onset
Diabetes Mellitus Type 2
Keywords: Polyphenols
Microbiota
Inflammation
Oxidative stress
Insulin resistance
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2024-11-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: To evaluate insulin resistance index
timeFrame: 5 years
measure: Analyze the significant differences between metabolomic profile before and after the dietetic intervention, and between both groups (flavonoid-enriched juice vs placebo)..
timeFrame: 5 years
Secondary outcomes:
measure: Assess significant changes in body fat mass percentage after the dietetic intervention.
timeFrame: 5 years
measure: To assess significant changes in triglycerides before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients.
timeFrame: 5 years
measure: To evaluate the composition and diversity of gut microbiota
timeFrame: 5 years
measure: To identify serum biomarkers using a metabolomic approach
timeFrame: 5 years
measure: Evaluate significant changes in % of weight loss after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
measure: To assess significant changes in LDLc before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients.
timeFrame: 5 years
measure: To assess significant changes in HDLc before and after the use of flavonoid-enriched juice and its placebo in the same groups of patients.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: Assess significant changes in C3 protein after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: Evaluate significant changes in ROS levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
measure: Assess significant improvements in glutathione levels after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
measure: Evaluate significant improvements in mitochondrial ROS production after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
measure: Analyze significant improvements in mitochondrial membrane potential after the dietetic intervention in both groups (flavonoid-enriched juice vs placebo) after the dietary intervention.
timeFrame: 5 years
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: FISABIO
Study officials:
References: