Clinical trial NCT05420311: Personalized or Precision Medicine in the Dietary Approach to Obesity
Official title: Personalized or Precision Medicine in the Dietary Approach to Obesity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Keywords: Precision medicine, nutrigenomics, microbiome, obesity, diet
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sponsor class: OTHER
First posted: 2022-06-15
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomized cross-over study testing three different dietary weight-loss interventions
Primary purpose: TREATMENT

Brief summary: The main objective of this project is to apply a precision medicine approach to try to explain the intra-individual variability of the response to different weight loss approaches: a balanced hypocaloric diet in macronutrients (MedDiet), a very low carbohydrate diet (KetoDiet) and an intermittent fasting (IF) approach, and try to establish in a personalized manner with the individual variability in genetics, metabolites, intestinal microbiome, and environmental factors the best dietary strategy for weight loss. As secondary objectives the investigators pretend to O1: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in insulin resistance, blood pressure, lipid levels and NASH markers after three different dietary interventions. O2: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in the body composition and the different ratio of free-fat/ fat mass loss after three different dietary interventions. O3: To determine the most effective intervention to increase the loss of fat mass, preserve the free-fat mass and trigger a better metabolic profile. O4: To follow-up changes in gut microbiota and DNA methylation after each of the cross-over dietary interventions. O5: To evaluate the transcriptional response of adipose tissue and elucidate its predictive value for the body-composition changes in patients subjected to the different dietary interventions.

O6: To evaluate the influence of D-ß-hydroxybutyrate as well as other short-chain acyl-CoA precursor metabolites in human adipocytes lipolysis by in vitro experimentation and elucidate the influence of metabolite-sensitive histone modifications in the shaping of adipose transcriptional program and lipolysis sensitivity. O7: To develop a machine learning algorithm based on genetics, epigenetics, intestinal microbiome, and environmental factors for the prediction of the best dietary approach for weight loss in a personalized manner. To try to respond to these objectives, the investigators will apply two models: a randomized cross-over study testing three different dietary weight-loss interventions: MedDiet, KetoDiet, and IF with wash-out periods before each intervention.

Detailed description: The main objective of this project is to apply a precision medicine approach to try to explain the intra-individual variability of the response to different weight loss approaches: a balanced hypocaloric diet in macronutrients (MedDiet), a very low carbohydrate diet (KetoDiet) and an intermittent fasting (IF) approach, and try to establish in a personalized manner with the individual variability in genetics, metabolites, intestinal microbiome, and environmental factors the best dietary strategy for weight loss. As secondary objectives the investigators pretend to O1: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in insulin resistance, blood pressure, lipid levels and NASH markers after three different dietary interventions. O2: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in the body composition and the different ratio of free-fat/ fat mass loss after three different dietary interventions. O3: To determine the most effective intervention to increase the loss of fat mass, preserve the free-fat mass and trigger a better metabolic profile. O4: To follow-up changes in gut microbiota and DNA methylation after each of the cross-over dietary interventions. O5: To evaluate the transcriptional response of adipose tissue and elucidate its predictive value for the body-composition changes in patients subjected to the different dietary interventions. O6: To evaluate the influence of D-ß-hydroxybutyrate as well as other short-chain acyl-CoA precursor metabolites in human adipocytes lipolysis by in vitro experimentation and elucidate the influence of metabolite-sensitive histone modifications in the shaping of adipose transcriptional program and lipolysis sensitivity. O7: To develop a machine learning algorithm based on genetics, epigenetics, intestinal microbiome, and environmental factors for the prediction of the best dietary approach for weight loss in a personalized manner. To try to respond to these objectives, the investigators will apply two models: a randomized cross-over study testing three different dietary weight-loss interventions: MedDiet, KetoDiet, and IF with wash-out periods before each intervention in patients with obesity; and a second cellular approach with adipose tissue from the patients as well as with commercial cells.

Eligibility criteria: Inclusion Criteria:

* Participants aged ≥ 18 and \<70 years old who were derived to the obesity-management unit of the Endocrinology and Nutrition Unit of the Virgen de la Victoria Hospital (Málaga).
* BMI between 35 and 45 kg/m2.

Exclusion Criteria:

* Pregnant or lactating
* Following a prescribed diet for any reason in the past 3 months
* Celiac disease, Crohn's disease or any condition altering nutritional requirements.
* Allergies or food intolerances, as well as antibiotics treatment or usual probiotics intake.

Primary outcomes:
measure: Changes in body weight after each intervention
timeFrame: From baseline to 1 month
Secondary outcomes:
measure: Changes in body composition and in the ratio of free-fat / fat mass loss after the three different dietary interventions.
timeFrame: From baseline to 1 month
measure: Changes in the degree of insulin resistance.
timeFrame: From baseline to 1 month
measure: Changes in the systolic blood pressure
timeFrame: From baseline to 1 month
measure: Changes in the diastolic blood pressure
timeFrame: From baseline to 1 month
measure: Changes in lipid profile (triglycerides)
timeFrame: From baseline to 1 month
measure: Changes in lipid profile (cholesterol)
timeFrame: From baseline to 1 month
measure: Changes in the degree of ketosis
timeFrame: From baseline to 1 month
measure: Changes in gut microbiota
timeFrame: From baseline to 1 month
measure: DNA methylation.
timeFrame: From baseline to 1 month
measure: Changes in the punctuation in neurocognitive test - Trailmaking Test (A - B)
timeFrame: From baseline to 1 month
measure: Changes in the punctuation in neurocognitive test - Stroop
timeFrame: From baseline to 1 month
measure: Changes in the punctuation in neurocognitive test - WAISspan
timeFrame: From baseline to 1 month
measure: Changes in the punctuation in neurocognitive test - UPPS-P
timeFrame: From baseline to 1 month
Other outcomes:
Locations:
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
Study officials:
affiliation: Instituto de Investigacion Biomedica de Malaga
name: Franscisco J. Tinahones, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
References: