Effect of Citrus Flavonoids on Obesity.

NCT06680635 | Completed

• 1 other identifier: PI21/01160
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity Adult Onset; Diabetes Mellitus Type 2

Keywords

Polyphenols; Microbiota; Inflammation; Oxidative stress; Insulin resistance

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (19)

• 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

Study Arms (2)

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).

Dietary Supplement: Flavonoid-enriched juice and a low-calorie diet

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).

Dietary Supplement: Food supplement: placebo juice and a low calorie diet

Interventions

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

Flavonoid-enriched juice and low-calorie diet for obese patients

Food supplement: placebo juice and a low calorie diet DIETARY_SUPPLEMENT

Placebo juice (200 ml/day) and a low calorie diet

Pacebo juice and low-calorie diet for obese patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celia Bañuls: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

FISABIO

Valencia, Valencia, 46020, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 6, 2024
• First Posted: November 8, 2024
• Study Start: January 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: January 31, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)