Microbiota in Dietary Approach to Obesity

NCT04453150 | Completed

• 1 other identifier: ISCIII CP18/01160
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut microbiota changes of different approaches for the weight reduction that increase the ketone bodies in a different proportion in relation to the classic hypocaloric diet. Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut microbiota and its relationship with anthropometric changes and of the Brown adipose tissue, Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic changes that may explain the changes found in the other objectives. Objective 6: Determine the safety of the diets that increase the ketone bodies compared to the classic hypocaloric diet, Objective 7: if the effects of the different dietary approaches are maintained during the medium time, and Objective 8: Verify in experimental models (microbiota transplants from humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies administration) the causality of the gut microbiota of these findings. Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).

Conditions

Obesity

Keywords

Ketosis; Microbiota

Outcome Measures

Primary Outcomes (1)

• Changes in gut microbiota composition

  To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months

  Baseline, 12 weeks

Secondary Outcomes (10)

• Changes in weight

  Baseline, 12 weeks

• Changes in body mass index.

  Baseline, 12 weeks

• Changes in waist circumference.

  Baseline, 12 weeks

• Changes in body composition.

  Baseline, 12 weeks

• Changes in brown adipose tissue.

  Baseline, 12 weeks

Study Arms (5)

Standard hypocaloric diet

EXPERIMENTAL

Mediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner).

Other: Standard hypocaloric die

Intermittent fasting 16/8 (early fasting)

EXPERIMENTAL

Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day).

Other: Intermittent fasting 16/8 (early fasting)

Intermittent fasting 16/8 (late fasting)

EXPERIMENTAL

Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day).

Other: Intermittent fasting 16/8 (late fasting)

Alternate-day fasting

EXPERIMENTAL

In this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein).

Other: Alternate-day fasting

Ketogenic diet

EXPERIMENTAL

Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein.

Other: Ketogenic diet

Interventions

Standard hypocaloric die OTHER

Standard hypocaloric diet

Standard hypocaloric diet

Intermittent fasting 16/8 (early fasting) OTHER

Intermittent fasting 16/8 (early fasting)

Intermittent fasting 16/8 (early fasting)

Intermittent fasting 16/8 (late fasting) OTHER

Intermittent fasting 16/8 (late fasting)

Intermittent fasting 16/8 (late fasting)

Alternate-day fasting OTHER

Alternate-day fasting

Alternate-day fasting

Ketogenic diet OTHER

Ketogenic diet

Ketogenic diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obesity (BMI≥30-45 kg/m2)

You may not qualify if:

• Type 2 diabetes mellitus
• Patients with major cardiovascular events in the 6 months prior to the study beginning.
• Previous or current history of inflammatory disease.
• Active infectious disease.
• The refusal of the patient to participate in the study
• Consumption of probiotics or prebiotics
• Antibiotic therapy in the 3 months prior to the study

Sponsors & Collaborators

• Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud: lead

Study Sites (1)

Virgen de la Victoria Hospital

Málaga, 29010, Spain

Location

Related Publications (2)

• Martinez-Montoro JI, Bandera B, Gutierrez-Bedmar M, Gomez-Perez AM, Macias-Gonzalez M, Moreno-Indias I, Tinahones FJ. Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial. BMC Med. 2025 Jul 1;23(1):368. doi: 10.1186/s12916-025-04182-z.

  PMID: 40598397 DERIVED

• Mela V, Heras V, Iesmantaite M, Garcia-Martin ML, Bernal M, Posligua-Garcia JD, Subiri-Verdugo A, Martinez-Montoro JI, Gomez-Perez AM, Bandera B, Moreno-Indias I, Tinahones FJ. Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis. Gut. 2025 Oct 8;74(11):1828-1846. doi: 10.1136/gutjnl-2025-335353.

  PMID: 40335161 DERIVED

MeSH Terms

Conditions

Obesity; Ketosis

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Francisco J. Tinahones, PhD

  Instituto de Investigacion Biomedica de Malaga

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: July 1, 2020
• Study Start: January 22, 2020
• Primary Completion: June 9, 2022
• Study Completion: June 22, 2022
• Last Updated: July 6, 2022

Record last verified: 2021-07

Locations

ES (1)