Clinical trial NCT05031572: Energy -Sensing Metabolites in Caloric Restriction
Official title: New Energy-sensing Metabolites: Beneficial Effects on Metabolic Health in Obesity Comparing Diary Caloric Restriction vs Intermittent Fasting. A Randomized Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Insulin Sensitivity/Resistance
Diabetes Type 2
Keywords: obesity
diabetes
intermittent fasting
energy-sensing metabolites
Lead sponsor: Institut Investigacio Sanitaria Pere Virgili
Sponsor class: OTHER
First posted: 2021-09-02
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: clinical study: randomized, cross-over design, study participants will consume either lifestyle recommendations for a healthy Mediterranean diet under a continued caloric restriction diet (DCR) or will undertake an intermittent (IF) protocol
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of glucose)
timeFrame: basal and after 8 weeks
measure: To investigate whether IF is better than DCR in terms of metabolic improvement through the study (change in the secretory pattern of insulin)
timeFrame: basal and after 8 weeks
measure: 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)
timeFrame: at beginning of week 12 vs week 20
measure: 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)
timeFrame: at beginning of week 12 vs week 20
Secondary outcomes:
measure: 1) the dynamics of gastrointestinal hormones and energy sensing metabolites
timeFrame: 8 weeks - 20 weeks
measure: 2) Analysis of microbial species in fecal samples (gut flora)
timeFrame: 8 weeks - 20 weeks
measure: variability on succinate after weight loss
timeFrame: 8 weeks - 20 weeks
measure: variability on Short-chain fatty acids (SCFAs) after weight loss
timeFrame: 8 weeks - 20 weeks
measure: variability on Medium-chain fatty acids (MCFAs) after weight loss
timeFrame: 8 weeks - 20 weeks
measure: variability on biliary acids (BA) after weight loss
timeFrame: 8 weeks - 20 weeks
Other outcomes:
Locations:
city: Tarragona
country: Spain
facility: Hospital Universitari Joan XXIII de Tarragona. IISPV
Study officials:
affiliation: Director
name: Joan J Vendrell, PhD
role: STUDY_DIRECTOR
References: