Circulating Microvesicles Regulating Metabolic Homeostasis in Obesity After Caloric Restriction Programs (TREV)

The Usefulness of Circulating Microvesicles (host and Bacterial) in Regulating Metabolic Homeostasis in Obesity Randomized Study of Parallel Arms in Obese Patients Undergoing Caloric Restriction Diet Vs. Early Time-restricted Eating

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Active Comparator: Continuous calorie restriction; Behavioral: eTRE

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juan José Vendrell Ortega, Professor; Phone Number: +34 619672912; Email: jvortega2002@gmail.com

Study Locations

• Spain
  • Tarragona, Spain, 43005
    • Recruiting
    • Hospital Universitario de Tarragona Juan XXIII
    • Contact: Juan Jose Vendrell Ortega, PhD, MD, Professor; Phone Number: +34 977295800; Email: jvortega2002@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous caloric restriction; Continuous calorie restriction diet based on healthy Mediterranean diet recommendations	Behavioral: Active Comparator: Continuous calorie restriction; Individualized continuous calorie restriction diet based on healthy Mediterranean diet recommendations aiming to achieve at least a 5% weight loss at the end of the intervention
Experimental: eTRE; early (morning) time-restricted eating (eTRE) plus continuous caloric restriction diet based on healthy Mediterranean diet recommendations	Behavioral: eTRE; early (morning) time-restricted eating pluss individualized continuous calorie restriction diet based on healthy Mediterranean diet recommendations aiming to achieve at least a 5% weight loss at the end of the intervention

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut and host microbiota-derived metabolites (I)	Changes in circulating short-chain fatty acids levels [µM]; assesed by Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS)	Before and after (12 weeks) of the intervention
Gut and host microbiota-derived metabolites (II)	Changes in circulating bile acids levels [nM]; Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)	Before and after (12 weeks) of the intervention
Gut and host microbiota-derived metabolites (III)	Changes in circulating succinate levels [µM]; assesed by EnzyChrom™ Succinate Assay Kit	Before and after (12 weeks) of the intervention
Entero-endocrine incretin hormones (I)	Changes in post-prandial response to a meal-tolerance test in serum levels of glucose [mg/dL]; assesed by ELISA kit	Before and after (12 weeks) of the intervention
Entero-endocrine incretin hormones (II)	Changes in post-prandial response to a meal-tolerance test in serum levels of insulin levels [pmol/L] ]assesed by ELISA kit	Before and after (12 weeks) of the intervention
Entero-endocrine incretin hormones (III)	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	Before and after (12 weeks) of the intervention
Entero-endocrine incretin hormones (IV)	Changes in post-prandial response to a meal-tolerance test in plasma levels of gastric inhibitory polypeptide (GIP) [pg/mL]; assesed by ELISA kit	Before and after (12 weeks) of the intervention
Microbial composition/metagenomic	Changes in alpha and beta diversity, relative abundance and functional metagenomics; assesed by Ilumina metagenomics	Before and after (12 weeks) of the intervention
Cellular energy metabolism	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	Before and after (12 weeks) of the intervention

Collaborators and Investigators

• Sponsor: Institut Investigacio Sanitaria Pere Virgili
• Investigators: Principal Investigator: Juan José Vendrell Ortega, Professor, Instituto de Investigación Sanitaria Pere Virgili (IISPV)

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: obesity; incretins; bile acids; caloric restriction; short-chain fatty acids; extracellular vesicles; brown fat; time-restricted feeding
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: PI23/01133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No