Circulating Microvesicles Regulating Metabolic Homeostasis in Obesity After Caloric Restriction Programs

Not Applicable

Recruiting

• Conditions: Obesity

• Registration Number: NCT06395246
• Lead Sponsor: Institut Investigacio Sanitaria Pere Virgili

Brief Summary

The main aim of the present study is to evaluate the effectiveness of two dietary protocols: Daily Caloric Restriction (DCR) and Early Time-Restricted Feeding + DCR (eTRE) on metabolic homeostasis and the influence of circulating extracellular vesicles (EVs) as inter-organ communication elements in obese patients.

Detailed Description

The specific objectives are:

1. To assess the effect of two dietary protocols on weight loss and metabolic benefits in non-morbidly obese subjects.

2. Influence of both protocols on energy signaling metabolites and the dynamics of enteroendocrine hormones.

3. Define the "digital footprint" of EVs as inter-organ communication elements influencing metabolic status in obese subjects.

The study design comprises a randomized parallel-arm design (n=40) with consecutive 1:1 allocation to a calorie restriction protocol for a healthy Mediterranean diet under Daily Caloric Restriction (DCR) (n=20) or an eTRE protocol (n=20) for 12 weeks. Clinical and analytical variables, adherence, satiety, chronotype, and brown fat content will be determined before and at the end of the follow-up. Derivatives of intestinal microbiota, short-chain fatty acids, bile acids, and circulating metabolites derived from host intermediary metabolism will be assessed through metabolomics. Glucagon-like peptide 1 (GLP1) and gastric inhibitory polypeptide (GIP) dynamics after a standard meal test. Metagenomics. Bioenergetic analysis of PBMC by SeaHorse. Total EV miRNA profile. Isolation of host and bacterial EVs. Characterization of the protein cargo of host and bacterial EVs.

Study Timeline

• Study First Submitted: 2024-04-24
• Study First Submitted QC: 2024-04-29
• Study First Posted: 2024-05-02
• Study Start: 2024-05-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-04
• Primary Completion: 2025-05-30
• Study Completion: 2025-12-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. age between 18 and 70 years old.
2. BMI ranges between 27 and 40 kg/ m2.
3. Absence of underlying pathology in medical and physical examination, except for those related to excess weight.
4. Signature of the informed consent for participation in the study.

Exclusion Criteria

1. Serious systemic disease not related to obesity, such as cancer, kidney or severe liver disease.
2. Systemic diseases with intrinsic inflammatory activity (autoimmune diseases such as rheumatoid arthritis and asthma).
3. Pregnancy and lactation.
4. Vegetarians or subjects subjected to an irregular diet.
5. Patients with severe eating disorders.
6. Patients with clinical symptoms and signs of infection in the previous month.
7. Patients with chronic anti-inflammatory steroid treatments and/or nonsteroidal anti-inflammatory drugs.
8. Recent antibiotic treatment.
9. Uncontrolled alcoholism or drug abuse.
10. Rotating or nocturnal shift workers.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Body composition (II)	Before and after (12 weeks) of the intervention	Changes in lean body mass (kg); assesed by bioimpedance monitoring device (Seca®)
Anthropometric measurements (II)	Before and after (12 weeks) of the intervention	Changes in body mass index (kg/m\^2);
Anthropometric measurements (V)	Before and after (12 weeks) of the intervention	Changes neck circumference (cm)
Anthropometric measurements (III)	Before and after (12 weeks) of the intervention	Changes waist circumference (cm)
Anthropometric measurements (IV)	Before and after (12 weeks) of the intervention	Changes hip circumference (cm)
Brown fat	Before and after (12 weeks) of the intervention	Changes in brown fat volume (cm3); assessed by magnetic resonance image (MRI)
Anthropometric measurements (I)	Before and after (12 weeks) of the intervention	Changes in weight (kg)
Body composition (I)	Before and after (12 weeks) of the intervention	Changes in fat body mass (kg); assesed by bioimpedance monitoring device (Seca®)
Body composition (III)	Before and after (12 weeks) of the intervention	Changes visceral adipose tissue (L); assesed by bioimpedance monitoring device (Seca®)

Secondary Outcome Measures

Name	Time	Method
Gut and host microbiota-derived metabolites (I)	Before and after (12 weeks) of the intervention	Changes in circulating short-chain fatty acids levels \[µM\]; assesed by Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS)
Microbial composition/metagenomic	Before and after (12 weeks) of the intervention	Changes in alpha and beta diversity, relative abundance and functional metagenomics; assesed by Ilumina metagenomics
Gut and host microbiota-derived metabolites (III)	Before and after (12 weeks) of the intervention	Changes in circulating succinate levels \[µM\]; assesed by EnzyChrom™ Succinate Assay Kit
Entero-endocrine incretin hormones (I)	Before and after (12 weeks) of the intervention	Changes in post-prandial response to a meal-tolerance test in serum levels of glucose \[mg/dL\]; assesed by ELISA kit
Entero-endocrine incretin hormones (II)	Before and after (12 weeks) of the intervention	Changes in post-prandial response to a meal-tolerance test in serum levels of insulin levels \[pmol/L\] \]assesed by ELISA kit
Gut and host microbiota-derived metabolites (II)	Before and after (12 weeks) of the intervention	Changes in circulating bile acids levels \[nM\]; Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Cellular energy metabolism	Before and after (12 weeks) of the intervention	Changes in Cluster of Differentiation 14 positive (CD14+) monocytes isolated from peripheral blood mononuclear cells (PBMCs) will be used for bioenergetics analysis via an extracellular flux analyzer
Entero-endocrine incretin hormones (III)	Before and after (12 weeks) of the intervention	Changes in post-prandial response to a meal-tolerance test in plasma levels of glucagon-like peptite 1 \[GLP-1 \] (pmol/L); assesed by ELISA kit
Entero-endocrine incretin hormones (IV)	Before and after (12 weeks) of the intervention	Changes in post-prandial response to a meal-tolerance test in plasma levels of gastric inhibitory polypeptide (GIP) \[pg/mL\]; assesed by ELISA kit

Trial Locations

Locations (1)

Hospital Universitario de Tarragona Juan XXIII; 🇪🇸 Tarragona, Spain