Energy -Sensing Metabolites in Caloric Restriction

New Energy-sensing Metabolites: Beneficial Effects on Metabolic Health in Obesity Comparing Diary Caloric Restriction vs Intermittent Fasting. A Randomized Cross-over Study

General integrated goal of the coordinated project:

To elucidate the role of succinate and other metabolites derived from the intestinal microbiota such as Short Chain Fatty Acids (SCFAs), as energy sensing metabolites in the context of obesity and type 2 diabetes (T2D).

Specific objectives of Subproject 1 (SP1): 1a. - To investigate whether intermittent fasting (IF) is better than Continued Daily Caloric Restriction (DCR) in terms of metabolic improvement through the study of: 1) the dynamics of gastrointestinal hormones and energy sensing metabolites, 2) the intestinal microbiome, 3) variability on succinate and SCFAs, MCFAs and Biliary Acid after weight loss; Methodology: clinical study: randomized, cross-over design, study participants (n=15) will consume either lifestyle recommendations for a healthy Mediterranean diet under a continued caloric restriction diet (DCR) or will undertake an intermittent (IF) protocol. Clinical, anthropometrical and functional studies. Metabolomics for gut derived metabolites in plasma. Enteroendocrine gastrointestinal dynamics. Metagenomic analysis.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Sensitivity/Resistance; Diabetes Type 2
• Intervention / Treatment: Other: dietary intervention

Detailed Description

To investigate whether IF is better than DCR in terms of metabolic improvement through the study of:

1. the dynamics of gastrointestinal hormones and energy sensing metabolites
2. the intestinal microbiome
3. variability on succinate and SCFAs MCFAs and BA after weight loss

Human study protocol:

A pilot clinical trial in human study participants will be assayed. Participants for intermittent fasting (IF) will be asked to fast for 24 hours on two days of the week (2/5 protocol).

1A.-Design: Utilizing a randomized, cross-over design, study participants (n=15) will consume either lifestyle recommendations for a healthy Mediterranean diet under a continued daily caloric restriction diet (DCR) or will undertake an intermittent (IF) protocol. Each study period will be 8 weeks - total study period will be 16 weeks + a 4-week washout period between dietary exposures. The study participants will be adults who have obesity with a Body Mass Index (BMI)25 kg/m2 and 40 kg/m2 and have no contraindications for intermittent fasting (see inclusion and exclusion criteria below).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Tarragona, Spain, 43005
    • Hospital Universitari Joan XXIII de Tarragona. IISPV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• White men and women between 18 and 65 years of age.
• BMI range between 25 and 40 kg/m2
• Absence of underlying pathology in medical and physical examination, except for those related to excess weight.
• Signature of the informed consent for participation in the study.

Exclusion Criteria:

• Serious systemic disease not related to obesity, such as cancer, kidney or severe liver disease.
• Systemic diseases with intrinsic inflammatory activity (autoimmune diseases such as rheumatoid arthritis and asthma)
• Pregnancy and lactation.
• Vegetarians or subjects subjected to an irregular diet.
• Patients with severe eating disorders.
• Patients with clinical symptoms and signs of infection in the previous month.
• Patients with chronic anti-inflammatory steroid treatments and/or nonsteroidal anti-inflammatory drugs.
• Recent antibiotic treatment.
• Psychiatric history.
• Uncontrolled alcoholism or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: conventional caloric restriction diet; (DCR protocol): lifestyle recommendations for a healthy Mediterranean diet under a continued daily caloric restriction diet	Other: dietary intervention; Chronic caloric restriction diet vs intermittent fasting on energy sensing metabolites and metabolic homeostasis
Other: Intermitent fasting; Fasting for two days (non-consecutive) out of seven, with the fasting days separated by at least one day.	Other: dietary intervention; Chronic caloric restriction diet vs intermittent fasting on energy sensing metabolites and metabolic homeostasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of glucose)	Plasma concentrations of glucose during a meal test	basal and after 8 weeks
To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of insulin)	Plasma concentrations of insulin during a meal test	basal and after 8 weeks
To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of glucose after crossing arm)	Plasma concentrations of glucose during a meal test	at beginning of week 12 vs week 20
To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of insulin after crossing arm)	Plasma concentrations of insulin during a meal test	at beginning of week 12 vs week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) the dynamics of gastrointestinal hormones and energy sensing metabolites	GLP-1; GLP-2 during a meal test	8 weeks - 20 weeks
2) Analysis of microbial species in fecal samples (gut flora)	intestinal microbiome after each interventional period	8 weeks - 20 weeks
variability on succinate after weight loss	quantification of succinate	8 weeks - 20 weeks
variability on Short-chain fatty acids (SCFAs) after weight loss	quantification of SCFAs	8 weeks - 20 weeks
variability on Medium-chain fatty acids (MCFAs) after weight loss	quantification of MACFAs	8 weeks - 20 weeks
variability on biliary acids (BA) after weight loss	quantification of BA	8 weeks - 20 weeks

Collaborators and Investigators

• Sponsor: Institut Investigacio Sanitaria Pere Virgili
• Investigators: Study Director: Joan J Vendrell, PhD, Director

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 9, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: diabetes; obesity; intermittent fasting; energy-sensing metabolites
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Diabetes Mellitus, Type 2; Obesity; Insulin Resistance
• Other Study ID Numbers: PI20/00338

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data sharing will be upon request directly to the PI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No