An observational study in Obesity, sponsored by Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta. Recruiting at 1 site in Spain. Open to participants aged 30 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-31.
Sponsored by Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta · Observational
Overweight and obesity are increasingly prevalent worldwide. These bodyweight disorders are closely related to deficiencies in the control of food intake. A potential yet unexplored mechanism to explain the loss of eating control is the interaction between the gut microbiota and the brain. The mechanisms underlying the communication between the gut microbiome and the host remain largely unexplored. These mechanisms could occur in part through small non-coding RNAs, called microRNAs (miRNAs). miRNAs regulate epigenetic mechanisms to control gene expression.
Two hypotheses have been proposed:
I. The interaction between the gut microbiota and the brain and its associated epigenetic changes play an important role in the overweight-related loss of eating control and metabolic imbalance.
II.The composition and functionality of the gut microbiota are associated with circulating microRNAs and glycemic variability and modify the effect of physical activity on cognitive parameters and brain microstructure (R2*).
The study includes a cross-sectional design (comparison of subjects with and without obesity) to evaluate parameters associated with food addiction through validated questionnaires. The metabolic and behavioral profiles of the cohort will be characterized. The medial prefrontal cortex connectivity will be studied using functional magnetic resonance imaging (fMRI). The composition and functionality of the gut metagenome of the subjects will be analyzed in association with metabolic and behavioral parameters and imaging data. miRNAs can act as mediators of epigenomics of the effects of the metagenome that impact the brain, therefore it will be analyzed a broad profile of miRNAs circulating in plasma.
The study includes a cross-sectional design (comparison of subjects with and without obesity) to assess parameters associated with food addiction through validated questionnaires. The metabolic and behavioral profile of the cohort and medial prefrontal cortex (mPFC) connectivity using fMRI will be characterized. The composition and functionality of the gut metagenome of these subjects will be analyzed in terms of its links to metabolic and behavioral parameters and imaging data. Since miRNAs may act as epigenomic mediators of metagenome effects impacting the brain, a broad profile of miRNAs circulating in plasma will also be analyzed.
Subjects and methods:
A cohort of subjects (n=100, 50% with obesity) will be recruited in whom parameters of food addiction (reward sensitivity, punishment sensitivity, and Yale Food Addiction Scale (YFAS 2.0 score) will be collected. The project will be carried out in subjects with obesity (25 men, 25 women, Body mass index (BMI) > = 30kg/m2) and subjects without obesity, similar in age and sex (25 men, 25 women, BMI \<30kg/m2). A comprehensive metabolic profile (body weight, glucose and lipid profile, insulin resistance, blood pressure, and plasma and fecal metabolomics) will be analyzed.
A. Cross-sectional study:
Patients with obesity previously scheduled at the Service of Endocrinology, Diabetes, and Nutrition (UDEN) of the Hospital "Dr. Josep Trueta" of Girona (Spain) will be recruited and studied. Subjects without obesity will also be recruited through a public announcement.
A glycemia sensor will be implanted for ten days, as well as an activity and sleep tracker device to record physical activity during this period of time. Interstitial subcutaneous glucose concentrations will be monitored on an outpatient basis for a period of time of 10 consecutive days using a glucose sensor validated by the FDA (Dexcom G6 ®). The sensor will be implanted on day 0 and will retire on day 10 mid-morning. Glucose records will preferably be evaluated on days 2 to 9 to avoid the bias caused by the insertion and removal of the sensor, which prevents a sufficient stabilization of the monitoring system. The characteristic glycemic pattern of each patient will be calculated on average from the profiles obtained on days 2 to 9.
After 10 days, urine and feces will be collected for the study of the gut microbiota. Subjects will undergo a fasting blood test and after eating, neuropsychological testing will be performed. Subsequently, the sensor and the device for monitoring physical activity/sleep will be removed. Lastly, fMRI will be done to evaluate the iron content in the brain (R2*) and the parameters of "Diffusion Tensor Imaging" in different brain territories. We will characterize mPFC connectivity in subjects in this cohort by resting-state functional MRI and structural connectivity by MRI.
The gut metagenomic composition and functionality associated with these cognitive traits, miRNA, and metabolites in plasma and brain imaging data will be studied.
Visit planning:
Visit 1(day 1): Physical examination, Nutritional survey, Bioimpedance, Densitometry, glycemia sensor, and activity and sleep tracker device. Consent form.
Visit 2 (day 10): Sample: blood, urine, and feces. Diet questionnaire, Neuropsychological assessment, Glycemia sensor withdrawal. Activity and sleep tracker device withdrawal, fMRI.
DATA COLLECTION OF SUBJECTS OF CROSS-SECTIONAL STUDY:
Clinical variables:
Laboratory variables: 15cc of blood will be extracted from fasted subjects to determine the following variables using the usual routine techniques of the clinical laboratory:
Stool samples collection: A stool sample will be provided from each patient. The sample should be collected at home or in the hospital, sent to the laboratory within 4 hours from the collection, fragmented, and stored at -80ºC.
Analysis of gut microbiota in stool:
*Fecal genomic DNA extraction and whole-genome sequencing. Total DNA will be extracted from frozen human stool using the QIAamp DNA mini stool kit (Qiagen, Courtaboeuf, France). DNA quantification will be performed with a Qubit 3.0 fluorometer (Thermo Fisher Scientific, Carlsbad, CA, USA). Subsequently, 1 ng of each sample (0.2 ng/μl) will be used for the preparation of shotgun libraries for high-throughput sequencing, using the Nextera DNA Flex Library Prep kit (Illumina, Inc., San Diego, CA, USA) according to the manufacturer's protocol. Sequencing will be performed on a NextSeq 500 sequencing system (Illumina) with 2 X 150-bp paired-end chemistry, at the facilities of the Sequencing and Bioinformatics Service of the FISABIO (Valencia, Spain).
Profile of circulating miRNAs: Additionally, to metabolomic analyses in urine samples, metabolomic analyses will be performed using techniques such as 1H-NMR and HPLC-MS/MS in plasma and stool samples.
The relevant gut microbiota identified in the human cohort will first be tested in Drosophila. High-throughput screening in Drosophila of the metabolic and behavioral effects of the gut microbiota identified in mice with loss of feeding control will be performed. Microbial strains obtained from the storage facilities will be cultured in high yield under conditions suitable for selecting aerotolerant bacteria to associate with flies. These bacteria will be used to generate mono-associated gnotobiotic flies, which will be analyzed for alterations in feeding behavior using the high-throughput quantitative flyPAD feeding assay. We will test both fully-fed flies and flies deprived of amino acids. Bacterial strains identified as modifiers of the drive to eat will be evaluated for their effects on fly metabolism using standard metabolomic approaches. This task will identify specific bacterial strains capable of modifying the feeding drive, and behavioral and metabolic responses of Drosophila.
The information will remain registered in a notebook and will be computerized in the database of the study.
STATICAL METHODS:
Sample size: There are no previous data showing expected differences for sample size estimation regarding glucose variability, physical activity, the composition of gut microbiota, and cognitive function. In a previous study, differences in brain iron content were observed in 20 obese vs. 20 nonobese subjects. Thus, the proposed sample size is at least 20 individuals per group, with balanced age and gender (pre-and postmenopausal women) representation.
Student's t-test for independent samples will be used to compare the variables of subjects with obesity vs subjects without obesity. Prior to statistical analysis, the data will be normalized using specific normalization procedures. Next, the normal distribution and homogeneity of variances will be tested. Parameters that do not meet these requirements will be logarithmically transformed (log10). Student's t-test for paired samples will be used to study differences before and after follow-up. Significant associations, whether positive or negative, will be studied further (simple linear and multivariate regression analysis).
Metagenomic analysis.
Raw counts will be transformed using a centered logarithmic transformation (clr) as implemented in the R package "ALDEx2". Bacterial species and functions associated with brain iron and circulating microRNAs will be identified using robust linear regression models such as those implemented in the R package. Limma R, adjusting for age, body mass index, sex, and years of education. Taxa and bacterial functions will be previously filtered so that only those with more than 10 reads in at least five samples will be selected. The p-values will be adjusted for multiple comparisons using sequential goodness of fit as implemented in the R package "SGoF". SGoF has been shown to perform particularly better than FDR methods with a high number of tests and low sample size, which is the case for large omics data sets. Statistical significance will be set at p adjusted \<0.1.
Continuos glucose monitoring
The glycemic risks and measures of variability to be assessed are standard deviation (SD), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), risk index (RI), low blood glucose index (LBGI), and high blood glucose index (HBGI). In addition, percent (%) time in range (70-180mg/dL), % time in euglycemia (70 - 140 mg/dL), hypoglycemia (\<70mg/dL), and hyperglycemia (>180 mg/dL). Measures of glycemia variability were calculated using Matlab software (R2018a).
11,522 studies on the registry are indexed under Obesity; 2,033 are open to participants now.
This study's planned enrollment of 116 is close to the median of 114 across 2,154 observational studies indexed under Obesity.
Browse Obesity studies →Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta is the lead sponsor of 31 studies on the registry; 9 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with obesity, without known type 2 diabetes, previously scheduled at the Service of Endocrinology, Diabetes, and Nutrition (UDEN) of the Hospital "Dr. Josep Trueta" of Girona (Spain) will be recruited and studied.
Subjects without obesity will also be recruited through a public announcement.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Concentration of advanced glycation end products (AGE) receptor agonists.
Enzyme-linked immunosorbent assay (ELISA).
Time frame: 10 days
Glycemic variability.
Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.
Time frame: 10 days
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
Time frame: 10 days
The glycaemic risk measured with low blood glucose index (LBGI)
Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic
Time frame: 10 days
The glycaemic risk measured with high blood glucose index (HBGI).
High blood glucose index (HBGI) is a parameter that quantifies the risk of glycaemic.
Time frame: 10 days
The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE).
measured in mg/dl
Time frame: 10 days
Minutes light sleep
Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.
Time frame: 10 days
Minutes deep sleep
Mean and standard deviation of minutes deep sleep measures by activity and sleep
Time frame: 10 days
Minutes rapid eye movement (REM)
Mean and standard deviation of minutes REM measures by activity and sleep tracker device.
Time frame: 10 days
Effect on gut microbiota.
Gut microbiota will be analysed by metagenomics and metabolomics.
Time frame: 2 months
Visual memory
It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visual memory.
Time frame: 10 days
Audioverbal memory
It will be measured by California Verbal Learning Test (CVLT). Minimum/maximum scale values (0-16), where 16 is a better audioverbal memory.
Time frame: 10 days
Depressive symptomatology
It will be measured by Patient Health Questionnaire-9 (PHQ-9). Minimum/maximum scale values (0-27), where ≥ 20 is severe depression.
Time frame: 10 days
Impulsivity
It will be measured by Impulsive Behavior Scale (UPPS-P). The test evaluates: Negative urgency (tendency to act rashly under extreme negative emotions), Lack of Premeditation (tendency to act without thinking), Lack of Perseverance (inability to remain focused on a task) and Sensation Seeking (tendency to seek out novel and thrilling experiences). All items are rated on a four point scale from 1 (strongly agree) to 4 (strongly disagree).
Time frame: 10 days
Food Addiction
It will be measured by Yale Food Addiction Scale.It is a symptom score from 0-11, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, for substance dependence. Food addiction is diagnosed if ≥3 symptoms are reported.
Time frame: 10 days
Behavioral inhibition
It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The scale of sensitivity to punishment is related to the behavioral inhibition system. It is made up of two subscales of 24 items each, where the higher the score, the greater the sensitivity to punishment.
Time frame: 10 days
Behavioral activation
It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The reward sensitivity scale is related to the behavioral activation system. It is made up of two subscales of 24 items each, where the higher the score, the greater the sensitivity to reward.
Time frame: 10 days
Visoconstructive function
It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visoconstructive function.
Time frame: 10 days
Selective and alternating attention
It will be measured by Trail making test (Part A y B).
Time frame: 10 days
Attention and working memory
It will be measured by the Digits subtest of Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV).
Time frame: 10 days
Inhibition
It will be measured by Stroop Color-Word Test.
Time frame: 10 days
Phonemic verbal fluency
It will be measured by PMR
Time frame: 10 days
Semantic verbal fluency
It will be measured by Animals test. The person must name as many animals as possible in 1 minute. The result is corrected by standard scores, according to age and level of education.
Time frame: 10 days
Binge eating disorder
It will be measured by Binge Eating Scale (BES). The BES is one of the most widely used measures to assess binge eating disorder symptomatology. The BES score ranges from 0 to 46 and its cut-off point is greater than or equal to 27. Subjects with scores higher than 27 are more likely to suffer from binge eating disorder.
Time frame: 10 days
Anxiety
It will be measured by State-Trait Anxiety Inventory (STAI). This questionnaire evaluates state anxiety (S) and trait anxiety (R) through 20 items each, with a likert-type response scale of four alternatives. In the case of state anxiety, the scale goes from 0 (not at all) to 3 (a lot), while for trait anxiety it goes from 0 (almost never) to 3 (almost always). The higher the score, the greater the anxiety in both concepts.
Time frame: 10 days
Facial recognition
It will be measured by Benton Facial Recognition Test. The participant is shown a face and then must recognize it among six faces placed together.
Time frame: 10 days
Emotion recognition
It will be measured by Pictures of Facial Affect. The participant will be shown pictures of people and has to recognize what emotion the subjects of the pictures are expressing ( happiness, sadness, etc.).
Time frame: 10 days
Effect on brain structure.
Brain structure will be assessed using magnetic resonance imaging.
Time frame: 10 days
Diffusion Tensor Imaging brain sequences
Diffusion Tensor Imaging was acquired at 1.5 T (Philips ingenia) using a single-shot spin echo sequence with echo-planar imaging (EPI), 50 contiguous slices, voxel size 2x2x2.5 mm3, TE/TR of 72/3581 ms/ms, a diffusion-weighting factor b = 800 s/mm2 and diffusion encoding along 32 directions.
Time frame: 24 hours
Brain iron accumulation
It will be assessed using magnetic resonance imaging using (R2\*)
Time frame: 24 hours
Resting-state functional brain sequences
It will be assessed using magnetic resonance imaging (T2\*-weighted echo-planar imaging). T2 \* relaxation data will be acquired with a multi-echo gradient sequence with 10 equidistant echoes (first echo = 4.6ms; echo spacing = 4.6ms; repetition time = 1300ms). The value value of T2 \* will be calculated by adjusting the simple exponential terms for the signal decay of the respective echo time values.
Time frame: 24 hours
Insulin resistance
It will be measured by HOMA
Time frame: 10 days
Markers of chronic inflammation: C-reactive protein, IL-6, adiponectin and soluble, tumor necrosis factor-α receptor fractions.
Enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR).
Time frame: 2 months
Glycosylated hemoglobin (HbA1c) value
Glycosylated hemoglobin (HbA1c) in % or mmol/mol
Time frame: 10 days
The percentage of time in hyperglycaemia (glucose level above 250 mg/dl)
Time frame: 10 days
The percentage of time in hypoglycaemia (glucose level below 70mg/dl)
Time frame: 10 days
The percentage of time in glucose range (glucose level below 100 mg/dl)
Time frame: 10 days
The percentage of time in glucose range (glucose level between 126-139 mg/dl)
Time frame: 10 days
The percentage of time in glucose range (glucose level between 140-199 mg/dl)
Time frame: 10 days
The percentage of time in glucose range (glucose level above 200 mg/dl)
Time frame: 10 days
Burned calories
Mean and standard deviation of burned calories measures by activity and sleep tracker device.
Time frame: 10 days
Steps
Mean and standard deviation of steps measures by activity and sleep tracker device.
Time frame: 10 days
Distance
Mean and standard deviation of distance measures by activity and sleep tracker device.
Time frame: 10 days
Minutes null activity
Mean and standard deviation of minutes null activity measures by activity and sleep tracker device.
Time frame: 10 days
Minutes slight activity
Mean and standard deviation of minutes slight activity measures by activity and sleep tracker device.
Time frame: 10 days
Minutes mean activity
Mean and standard deviation of minutes mean activity measures by activity and sleep tracker device.
Time frame: 10 days
Minutes high activity
Mean and standard deviation of minutes high activity measures by activity and sleep tracker device.
Time frame: 10 days
Calories
Mean and standard deviation of calories measures by activity and sleep tracker device.
Time frame: 10 days
Minutes asleep
Mean and standard deviation of minutes asleep measures by activity and sleep tracker device.
Time frame: 10 days
Minutes awake
Mean and standard deviation of minutes awake measures by activity and sleep tracker device.
Time frame: 10 days
Bed time
Mean and standard deviation of bed time measures by activity and sleep tracker device.
Time frame: 10 days
Number time awake
Mean and standard deviation of number time awake measures by activity and sleep tracker device.
Time frame: 10 days
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Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta