Personalized or Precision Medicine in the Dietary Approach to Obesity

Obesity Clinical Trial

— PI21/01677  

Official title:

Personalized or Precision Medicine in the Dietary Approach to Obesity

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05420311
• Other study ID #: PI21/01677
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 31, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2022
• Source: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Contact: Isabel Moreno Indias, PhD.
• Phone: 951032647
• Email: Isabel.moreno[@]ibima.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: December 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Obesity

Intervention

Other:
• MedDiet Arm
A balanced hypocaloric diet in macronutrients (MedDiet)
• KetoDiet Arm
A very low carbohydrate diet (KetoDiet).
• IF Arm
An intermittent fasting (IF) approach

Locations

Country	Name	City	State
Spain	Hospital Universitario Virgen de la Victoria	Málaga

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in body weight after each intervention	Weight in kg	From baseline to 1 month
Secondary	Changes in body composition and in the ratio of free-fat / fat mass loss after the three different dietary interventions.	Ratio in %	From baseline to 1 month
Secondary	Changes in the degree of insulin resistance.	Measured by the HOMA-IR ratio	From baseline to 1 month
Secondary	Changes in the systolic blood pressure	Blood pressure measured in millimeters of mercury	From baseline to 1 month
Secondary	Changes in the diastolic blood pressure	Blood pressure measured in millimeters of mercury	From baseline to 1 month
Secondary	Changes in lipid profile (triglycerides)	Measured in mg/dl	From baseline to 1 month
Secondary	Changes in lipid profile (cholesterol)	Measured in mg/dl	From baseline to 1 month
Secondary	Changes in the degree of ketosis	Measured in mmol/l	From baseline to 1 month
Secondary	Changes in gut microbiota	Change from baseline in 16S rRNA amplicons after 1 month	From baseline to 1 month
Secondary	DNA methylation.	Measured by a Methylation Array of the whole genome interrogating 850000 CpGs.	From baseline to 1 month
Secondary	Changes in the punctuation in neurocognitive test - Trailmaking Test (A - B)	Trailmaking Test (A - B) allows evaluating visual search speed, working memory, motor skills, visual-spatial sequencing, sustained attention, divided attention and mental flexibility (time: reduction in seconds)	From baseline to 1 month
Secondary	Changes in the punctuation in neurocognitive test - Stroop	Stroop measures selective attention and inhibitory control. (increasing scores)	From baseline to 1 month
Secondary	Changes in the punctuation in neurocognitive test - WAISspan	Letters and numbers from the WAISspan for working memory, concentration, auditory sequencing and executive attention. (time: reduction in seconds)	From baseline to 1 month
Secondary	Changes in the punctuation in neurocognitive test - UPPS-P	Trailmaking Test (A - B) allows evaluating visual search speed, working memory, motor skills, visual-spatial sequencing, sustained attention, divided attention and mental flexibility (time: reduction in seconds); Stroop: Measures selective attention and inhibitory control. (increasing scores); Letters and numbers from the WAISspan for working memory, concentration, auditory sequencing and executive attention. (time: reduction in seconds); UPPS-P: Impulse BehaviorScale (Cyders et al. 2007; validated in Spanish by Candido et al, 2012). Self- administered scale that evaluates impulsivity. Scale of items using a 4-point likert scale (min 59 /max 136 points).	From baseline to 1 month