Clinical trial NCT06395246: Circulating Microvesicles Regulating Metabolic Homeostasis in Obesity After Caloric Restriction Programs
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Keywords: obesity
extracellular vesicles
incretins
bile acids
short-chain fatty acids
time-restricted feeding
caloric restriction
brown fat
Lead sponsor: Institut Investigacio Sanitaria Pere Virgili
Sponsor class: OTHER
First posted: 2024-05-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized parallel-arm design (n=40) with consecutive 1:1 allocation to either a continuous calorie restriction diet (n=20) for a healthy Mediterranean diet or an early time-restricted eating protocol + continuous caloric restriction (n=20) over 12 weeks.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Anthropometric measurements (I)
timeFrame: Before and after (12 weeks) of the intervention
measure: Anthropometric measurements (II)
timeFrame: Before and after (12 weeks) of the intervention
measure: Anthropometric measurements (III)
timeFrame: Before and after (12 weeks) of the intervention
measure: Anthropometric measurements (IV)
timeFrame: Before and after (12 weeks) of the intervention
measure: Anthropometric measurements (V)
timeFrame: Before and after (12 weeks) of the intervention
measure: Body composition (I)
timeFrame: Before and after (12 weeks) of the intervention
measure: Body composition (II)
timeFrame: Before and after (12 weeks) of the intervention
measure: Body composition (III)
timeFrame: Before and after (12 weeks) of the intervention
measure: Brown fat
timeFrame: Before and after (12 weeks) of the intervention
Secondary outcomes:
measure: Gut and host microbiota-derived metabolites (I)
timeFrame: Before and after (12 weeks) of the intervention
measure: Gut and host microbiota-derived metabolites (II)
timeFrame: Before and after (12 weeks) of the intervention
measure: Gut and host microbiota-derived metabolites (III)
timeFrame: Before and after (12 weeks) of the intervention
measure: Entero-endocrine incretin hormones (I)
timeFrame: Before and after (12 weeks) of the intervention
measure: Entero-endocrine incretin hormones (II)
timeFrame: Before and after (12 weeks) of the intervention
measure: Entero-endocrine incretin hormones (III)
timeFrame: Before and after (12 weeks) of the intervention
measure: Entero-endocrine incretin hormones (IV)
timeFrame: Before and after (12 weeks) of the intervention
measure: Microbial composition/metagenomic
timeFrame: Before and after (12 weeks) of the intervention
measure: Cellular energy metabolism
timeFrame: Before and after (12 weeks) of the intervention
Other outcomes:
Locations:
city: Tarragona
country: Spain
facility: Hospital Universitario de Tarragona Juan XXIII
Study officials:
affiliation: Instituto de Investigación Sanitaria Pere Virgili (IISPV)
name: Juan José Vendrell Ortega, Professor
role: PRINCIPAL_INVESTIGATOR
References: