Clinical trial NCT06782009: Metabolic Impact on the Mitochondria-gut Microbiota Axis of Failure to Follow Restrictive Dietary Interventions in Subjects Living With Obesity
Official title: Metabolic Impact on the Mitochondria-gut Microbiota Axis of Failure to Follow Restrictive Dietary Interventions in Subjects Living With Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Keywords: dietary restrictions
intermittent fasting
mitochondrial function
gut microbiota
ketogenic diet
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2025-01-17
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The groups will receive the treatment simultaneously
Primary purpose: TREATMENT

Brief summary: Nutritional interventions with dietary restrictions have become highly popular for promoting weight and body fat loss; In addition, they are largely associated with the improvement and preservation of mitochondrial function as well as the changes they generate in the composition of the gut microbiota and microbial metabolites. During obesity, mitochondrial dysfunction in monocytes can increase low-grade inflammation and contribute to alterations in various metabolic tissues. There have been many studies that have been dedicated to describing the benefits and mechanisms of the use of restrictive interventions, but few have focused on further monitoring and evaluating the metabolic changes that occur due to the lack of follow-up of the use of these interventions, where subjects resume eating patterns with energy overload. behavior that happens in the vast majority of patients, so keeping mitochondria in good condition is a key aspect of maintaining health. The present project aims to study the metabolic changes that are generated by the lack of follow-up of restrictive dietary interventions, focusing on the effects produced in mitochondrial function evaluated in monocytes isolated from peripheral blood and the impact that the composition of the intestinal microbiota is generated from the metabolites produced, affecting as a consequence the inflammatory state of the host. A randomized controlled clinical trial will be carried out where the selected participants will be assigned by lottery to one of the 3 nutritional interventions for 8 weeks, then the participants will be followed up at 8, 16 and 24 weeks after the intervention has ended. Anthropometric and biochemical parameters, resting energy expenditure, blood pressure, oxidative stress markers, metabolomics, gut microbiota composition, and mitochondrial function will be evaluated during follow-up.

Detailed description: The study consists of an open-label randomized controlled clinical trial. The selected subjects will be men or women over 18 years of age with a body mass index (BMI) greater than or equal to 30 kg/m2, who meet the selection criteria, the subjects who will be randomly assigned to one of 3 dietary intervention groups. The study consisted of a dietary intervention with a duration of 8 weeks and a follow-up of 24 weeks after dietary intervention.

The intervention groups will be as follows:

1. Calorie-restricted diet: Dietary recommendations will be given restricting 30% in energy (kcal) according to their usual diet with normal macronutrient distribution (20-30% protein, 50-60% carbohydrates, 20-30% fats).
2. Intermittent fasting diet: Dietary recommendations will be given according to the energy expenditure determined by indirect calorimetry with normal macronutrient distribution. Intermittent fasting will be used with a time-restricted model of 16:8. For 16 hours, they will not be able to eat or drink calories. In the other 8 hours, they need to adhere to the energy-restricted diet.
3. Ketogenic diet: Recommendation will be given according to the energy expenditure determined by indirect calorimetry, with the following distribution of macronutrients: 20-25% protein, 5-10% carbohydrates, 70-80% fat.

Participants with calorie-restriction, intermittent fasting, or ketogenic diet dietary intervention will be provided with a food menu guide for fifteen days. After 8 weeks of the assigned intervention, patients will be provided with general dietary recommendations and will be invited to three more follow-up visits at 8, 16 and 24 weeks post-intervention. In addition, all participants will be provided with general recommendations for a physical activity plan for people living with obesity.

To evaluate adherence to treatment, participants will be asked to fill out 2 logbooks every two weeks (1 during the week and 1 for the weekend) in which they must record the type, amount and place where they consumed the food at each feeding time. They will also be called once a week for a 24-hour reminder. Participants on the ketogenic diet will be given test strips to measure ketones in urine.

Eligibility criteria: Inclusion Criteria:

* Male and female.
* Adults \>18 years of age.
* BMI ≥ 30 kg/m2

Exclusion Criteria:

* Patients with any type of diabetes.
* Patients with high blood pressure.
* Patients with acquired diseases secondarily producing obesity and diabetes.
* Patients who have suffered a cardiovascular event.
* Patients who at the screening visit presented glucose values greater than 126 mg/dL, triglycerides greater than 350 mg/dL, cholesterol greater than 300mg/dL and/or creatinine greater than 1.2 mg/dL in men and greater than 1 mg/dL in women.
* Patients with gastrointestinal diseases.
* Weight loss \> 3 kg in the last 3 months.
* Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
* Pregnancy status.
* Positive smoking.
* History of major surgery requiring general or regional anesthesia, respiratory support, and involving a recovery time longer than 2 weeks, such as surgeries of the abdomen (bowel resection), chest, head, and neck.
* Diagnosis of Anxiety and Depression as Determined by the HADS Scale
* Drug treatment:
* Antihypertensive drugs or treatment
* Treatment with hypoglycemic agents or insulin and antidiabetic drugs.
* Treatment with statins, fibrates or other drugs to control dyslipidemia.
* Use of antibiotics in the three months prior to the study.
* Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
* Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
* Supplements with any of the functional foods used in the study.
* Probiotic, prebiotic or symbiotic supplements.

Primary outcomes:
measure: Mitochondrial function
timeFrame: baseline to 8, 16, 24 and 32 weeks
Secondary outcomes:
measure: Gut microbiota composition
timeFrame: baseline to 8, 16 and 32 weeks
measure: Body weight measurement
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Glucose concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Cholesterol concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: HDL cholesterol concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: LDL cholesterol concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Triglycerides concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Insulin concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Leptin concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Interleukins concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: C-reactive protein concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: TNF-a concentration
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Alpha diversity of gut microbiota
timeFrame: baseline to 8, 16 and 32 weeks
measure: Beta diversity of gut microbiota
timeFrame: baseline to 8, 16 and 32 weeks
measure: Fat mass percentage
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Lean mass percentage
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Skeletal muscle mass percentage
timeFrame: baseline to 8, 16, 24 and 32 weeks
measure: Change of metabolites in serum
timeFrame: baseline to 8, 16 and 32 weeks
measure: Change of metabolites in feces
timeFrame: baseline to 8, 16 and 32 weeks
measure: Determination of valvular function
timeFrame: baseline to 8 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Tlalpan
city: Mexico City
country: Mexico
facility: Departamento de Fisiología de la Nutrición. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Laura A Velazquez Villegas, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clin Nutr. 2024 Aug;43(8):1914-1928. doi: 10.1016/j.clnu.2024.06.036. Epub 2024 Jul 5.
citation: Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Reply - Letter to the editor- enhancing understanding of dietary interventions in obesity: Insights and recommendations for future research. Clin Nutr. 2024 Sep;43(9):2211-2213. doi: 10.1016/j.clnu.2024.08.006. Epub 2024 Aug 13. No abstract available.