Clinical trial NCT02737267: Development of a Nutrigenetic Test for Personalized Prescription of Body Weight Loss Diets (Obekit)
Official title: Development of a Nutrigenetic Test for Personalized Prescription of Body Weight Loss Diets (Obekit)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Body Weight Changes
Keywords: Genetics
Polymorphism
Epigenetics
Metagenomics
Metabolomics
Metabolic syndrome conditions
Precision nutrition
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2016-04-13
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the relationship between several genetic variants and the response to a hypocaloric diet, in order to design a genetic test which permits prescribe the more personalized diet for each individual according to her genotype. Half of the participants will assigned to a moderate high protein diet, while the other half will assigned to a high carbohydrate diet.

Detailed description: Obesity has reached epidemic proportions becoming a major global public health challenge since it is associated with an increased risk of type 2 diabetes, cardiovascular disease, stroke, arthritis and some forms of cancer. Therefore, a large number of strategies have been investigated in order to induce a negative energy balance and consequently body weight loss mainly inducing a low calorie diet and sometimes accompanied by an increase in physical activity. However, individual responses to body weight loss interventions vary widely and several studies have aimed to identify psychological, behavioral and personal predictors of this variability.

In this context, the hypothesis of the present study is that part of the interindividual variability in relation to the success of certain weight loss treatments is based on gene-diet interactions. Depending on the composition of the diet and the genotype of each individual, it is more or less easy to reduce and maintenance body weight.

After the recruitment and selection of the study participants, the study will consists of a 4-month hypocaloric diet ("body weight loss period") followed by a second 6-month period ("body weight maintenance period") in which the subjects of the study will continue with the diet, but without any energy restriction. The participants will assigned to one of the two hypocaloric diets (-30% of the studied requirements for each individual) with different macronutrient composition:

* Moderately high protein diet: 40% of the energy derived from carbohydrates, 30% of the energy derived from protein and 30% of the energy derived from fat.
* Low fat diet: 60% of the energy derived from carbohydrates, 30% of the energy derived from protein and 30% of the energy derived from fat.

A group of normal weight individuals (n 12) will be recruited in order to compare the different parameters obtained in the obese subjects with those of normal population. They will be not subjected to any intervention.

Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) between 25 and 40 kg/m2
* Physical examination and vital signs normal, or is considered abnormal, but clinically insignificant by researcher.
* In the case of individuals with chronic stable dose drug treatment and during the last 3 previous months at baseline, the investigator will assess their possible inclusion.

Exclusion Criteria:

* BMI less than 25 or higher than 40 kg/m2
* Pregnant women
* Breastfeeding period. If artificial feeding until 6 months after birth.
* Type 1 diabetes
* Severe kidney diseases
* Severe digestive system diseases
* Electrolyte disorders (disorders of sodium, potassium, calcium, chlorine, phosphorus, magnesium)
* Acute cardiovascular diseases
* Cancer
* Anemia
* Eating disorders
* Recent prescription drug treatment (without stable doses scheduled)
* Drug therapy that can influence weight loss as corticosteroids.
* Some type of cognitive impairment and / psychic
* Subjects in which poor collaboration or, in the investigator's opinion, have difficulty following the procedures of the study is foreseen
* Lack of commitment (at the discretion of the investigator) with the intervention, suspected non-compliance, or real difficulties to follow the development of the study.

Primary outcomes:
measure: Change in body weight at Week 16
timeFrame: Baseline and 16 Weeks
measure: Change in body weight at Week 40
timeFrame: 16 Weeks and 40 Weeks
Secondary outcomes:
measure: Height
timeFrame: Baseline
measure: Change in waist and hip circumferences at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Change in waist and hip circumferences at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Change in body fat mass at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Change in body fat mass at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Single nucleotide polymorphisms (SNPs)
timeFrame: Baseline
measure: Changes in DNA methylation levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in DNA methylation levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in metabolic profiling at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in metabolomic profile at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in lipidomic profile at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in lipidomic profile at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in proteomic profile at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in proteomic profile at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in gut microbiota composition at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in gut microbiota composition at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in messenger ribonucleic acid (mRNA) expression at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in mRNA expression at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in microARNs in exosomes at 16 weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in microARNs in exosomes at 40 weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in DNA oxidation at 16 weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in DNA oxidation at 40 weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum glucose levels at 16 Weeks
timeFrame: Baseline and 16 weeks
measure: Changes in serum glucose levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum insulin concentration at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum insulin concentration at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum lipid metabolism markers at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum lipid metabolism markers at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum total protein concentration at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum total protein concentration at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum uric acid levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum uric acid levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum transaminases concentrations at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum transaminases concentrations at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum homocystein concentration at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum homocystein concentration at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in vascular endothelial growth factor (VEGF) at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in vascular endothelial growth factor (VEGF) at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in asymmetric dimethylarginine (ADMA) at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in asymmetric dimethylarginine (ADMA) at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in PAI-1 concentration at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasminogen activator inhibitor-1 (PAI-1) concentration at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in nitric oxide levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in nitric oxide levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in blood pressure at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in blood pressure at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in plasma C-Reactive Protein levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasma C-Reactive Protein levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasma IL-6 and IL-10 levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in plasma tumor necrosis factor-alpha (TNF-alpha) levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasma TNF-alpha levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in adiponectin levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in adiponectin levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in chemerin levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in chemerin levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in leptin levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in leptin levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in apelin levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in apelin levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in haptoglobin levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in haptoglobin levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in amyloid A levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in amyloid A levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in leukocytes levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in leukocytes levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in plasma LDL-ox levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasma LDL-ox levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in glutathione peroxidase activity at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in glutathione peroxidase activity at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in reduced and oxidized glutathione levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in reduced and oxidized glutathione levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in superoxide dismutase levels at 16 Weeks
timeFrame: Baseline ant 16 Weeks
measure: Changes in superoxide dismutase levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in serum isoprostanes levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in serum isoprostanes levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in plasma malonyldialdehyde (MDA) concentration at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in plasma malonyldialdehyde (MDA) concentration at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in monoamines levels at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in monoamines levels at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in physical activity at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in physical activity at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in depression degree at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in depression degree at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in anxiety degree at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in anxiety degree at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in the chronotype at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in the chronotype at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
measure: Changes in food intake at 16 Weeks
timeFrame: Baseline and 16 weeks
measure: Changes in food intake at 40 Weeks
timeFrame: Baseline and 40 weeks
measure: Changes in satiety at 16 Weeks
timeFrame: Baseline and 16 Weeks
measure: Changes in satiety at 40 Weeks
timeFrame: 16 Weeks and 40 Weeks
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Centre for Nutrition Research, University of Navarra
state: Navarra
Study officials:
affiliation: Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain
name: J. Alfredo Martínez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CIMA, University of Navarra
name: Fernando J. Corrales, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain
name: Femín I Milagro, PhD
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Jose Ignacio Riezu, PhD
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Carlos González-Navarro, PhD
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Marta Cuervo, PhD
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Iosune Zubieta
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Blanca Esther Martínez de Morentin, MD
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra
name: Leticia Goñi
role: STUDY_CHAIR
affiliation: Centre for Nutrition Research, University of Navarra. CIBER Obesity and Physiopathology of Nutrition (CIBERobn), Institute of Health Carlos III Madrid Spain
name: Santiago Navas, PhD
role: STUDY_CHAIR
References:
citation: Cuevas-Sierra A, Milagro FI, Guruceaga E, Cuervo M, Goni L, Garcia-Granero M, Martinez JA, Riezu-Boj JI. A weight-loss model based on baseline microbiota and genetic scores for selection of dietary treatments in overweight and obese population. Clin Nutr. 2022 Aug;41(8):1712-1723. doi: 10.1016/j.clnu.2022.06.008. Epub 2022 Jun 16.
citation: Cuevas-Sierra A, Romo-Hualde A, Aranaz P, Goni L, Cuervo M, Martinez JA, Milagro FI, Riezu-Boj JI. Diet- and sex-related changes of gut microbiota composition and functional profiles after 4 months of weight loss intervention. Eur J Nutr. 2021 Sep;60(6):3279-3301. doi: 10.1007/s00394-021-02508-0. Epub 2021 Feb 16.
citation: Ramos-Lopez O, Cuervo M, Goni L, Milagro FI, Riezu-Boj JI, Martinez JA. Modeling of an integrative prototype based on genetic, phenotypic, and environmental information for personalized prescription of energy-restricted diets in overweight/obese subjects. Am J Clin Nutr. 2020 Feb 1;111(2):459-470. doi: 10.1093/ajcn/nqz286.
citation: Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Goni L, Cuervo M, Martinez JA. Differential lipid metabolism outcomes associated with ADRB2 gene polymorphisms in response to two dietary interventions in overweight/obese subjects. Nutr Metab Cardiovasc Dis. 2018 Feb;28(2):165-172. doi: 10.1016/j.numecd.2017.11.006. Epub 2017 Dec 5.