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CompletedNCT03889132IRONMET+CGMUpdated Mar 31, 2026

Glucose, Brain and Microbiota

An observational study in Obesity, sponsored by Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta. Completed 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

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
128
Ages
30 Years to 65 Years
Sex
All
01

Study summary

The accumulation of iron is known to affect the functions of the liver, adipose tissue and muscle. The brain is a well-known place of iron deposition, which is associated with cognitive parameters of subjects with obesity.

The hypothesis is that certain parameters related to glucose metabolism (glycemic variability, the circulating concentration of AGE receptor agonists, pentosidine and HbA1c) are associated with cognitive function, brain iron content and gut microbiota composition in subjects with obesity.

The study includes both a cross-sectional (comparison of subjects with and without obesity) and a longitudinal design (evaluation one year after weight loss induced by bariatric surgery or by diet in patient with obesity) to evaluate the associations between continuous glucose monitoring, brain iron content (by magnetic resonance), cognitive function (by means of cognitive tests), physical activity (measured by activity and sleep tracker device) and the composition of the microbiota, evaluated by metagenomics.

Read the detailed description

Subjects and methods:

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 blood glucose 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 in on day 0 and will retire on day 10 midmorning. 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.

At the end of the week an magnetic resonance imaging will be done to evaluate the iron content in the brain and parameters of "Diffusion Tensor Imaging" in different brain territories.

Cognitive tests will be carried out and feces will be collected for the study of the microbiota.

The project will be carried out in subjects with obesity (20 men, 20 premenopausal women and 20 women postmenopausal, BMI > = 30kg/m2) and subjects without obesity, similar in age, sex and menopausal status (20 men, 20 premenopausal women and 20 postmenopausal women, BMI \<30kg/m2).

B. Longitudinal study:

After one year of follow-up, in which, subjects with obesity will undergo conventional treatment (hypocaloric diet and physical activity advise) or bariatric surgery for weight loss, a second visit will be carried out.

For comparison, the same protocol of the cross-sectional study will be done again. See information above.

Data collection of subjects of cross-sectional and longitudinal studies:

  • Subsidiary data: Age, sex and birth date.
  • Clinical variables: Weight, height, body mass index, waist and hip perimeters, waist-to-hip ratio, blood pressure (systolic and diastolic), fat mass and fat free-mass (bioelectric impedance and DEXA), smoking status, alcohol intake, registry of usual medicines and registry of antecedent relatives with obesity, diabetes and comorbidities.
  • 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 (hemogram, glucose, bilirubin, aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), gamma-glutamyl transpeptidase (GGT), urea, creatinine, uric acid, total proteins, albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glycated haemoglobin (HbA1c), ferritin, soluble transferrin receptor, ultrasensitive C reactive protein, erythrocyte sedimentation rate, lipopolysaccharide binding protein, free thyroxine (free T4), thyroid stimulating hormone (TSH) and baseline cortisol). An additional 15cc of blood (plasma-EDTA) will be extracted for further analyses.
  • 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.
  • Magnetic Resonance Imaging: All MRI examinations will be performed on a 1.5-T scanner (Ingenia ®; Philips Medical Systems). First, fluid-attenuated inversion recovery (FLAIR) sequence will be used to exclude subjects with preexisting brain lesions. Brain iron load will be assessed by means of R2* values. T2* relaxation data will be acquired with a multi-echo gradient-echo sequence with 10 equally spaced echoes (first echo=4.6ms; inter echo spacing=4.6ms; repetition time=1300ms). T2* will be calculated by fitting the single exponential terms to the signal decay curves of the respective multi-echo data.R2* values will be calculated as R2*=1/T2* and expressed as Hz. In addition, R2* values will be converted to μmol Fe/g units as previously validated on phantom tests. Brain iron images from control subjects will be normalized to a standard space using a template image for this purpose (EPI MNI template). Subsequently, all normalized images will be averaged for the determination of normal iron content. Normal values (mean and SD) will be also calculated for anatomical regions of interest using different atlas masks, addressing possible differences between gender and age. The brain iron comparison between control and obese subjects will be performed using voxel-based analysis. Obese-subjects images will be normalized to a standard space. The normalized image will be compared to normal population using t-test analysis with age and sex as co-variables. As result, a parametric map will show individual differences in iron deposition. Based on previous observational studies showing increased brain iron load at some specific regions and the evidence suggesting hippocampal and hypothalamic changes in association with obesity and insulin resistance, the statistical and image analyses will be focused on iron differences at the caudate, lenticular, thalamus, hypothalamus, hippocampus, and amygdala.
  • Neuropsychological examination: General cognitive functioning will be measured using the Vocabulary and Similarities subtests of the Wechsler Adult Intelligence Scale-III (WAIS-III); attention and working memory by the Forward and Backward Digit Span subtest of the WAIS-II; memory using the California Verbal Learning Test II; executive functions by the Trail Making Test, the Color-Word Stroop Test and the Verbal Fluency; mood using the Patient Health Questionnaire-9 and impulsive behaviors using the Iowa Gambling Task.
  • Microbiota composition: the microbiota composition will be analyzed according to a previous described protocol. 16s rRNA qPCR and LPS-binding protein in blood samples will be used for detection of bacterial translocation.

The information will remain registered in a notebook and will be computerized in the database of the study.

Statistical methods:

Sample size: There are no previous data showing expected differences for sample size estimation regarding glucose variability, physical activity, 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.

Statistical analyses: Firstly, normal distribution and homogeneity of variances will be tested. To determine differences between study groups, it will be used χ2 for categorical variables, unpaired Student's t-test in normal quantitative and Mann-Whitney U test for non-normal quantitative variables. Nonparametric Spearman analysis will be used to determine the correlation between quantitative variables. The same tests will also be used to study differences before and after follow-up. The significant associations, whether positive or negative, will be explored more-in-depth (simple and multivariate linear regression analyses).

The microbiota composition will be analyzed and compared using HeatMaps, Principal Component Analysis (PCA) and PLSDA. For multivariate statistics (PLSDA and hierarchical clustering), variables comprising morphological tissue characteristics, gut microbiota and functional test will be log transformed, filtered using interquartile range estimate and scaled using auto-scaling calculation (mean-centered and divided by the standard deviation of each variable) by using the Metaboanalyst ® platform, the R ® package ropls and MATLAB ® scripts. Alpha and beta biodiversity will be compared according to obesity, insulin resistance and iron status. It will also be used SPSS ® statistical software and Minitab ®.

02

Conditions studied

  • Obesity

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Keywords

  • Obesity
  • Continous Glucose Monitoring
  • Cognition
  • Brain Iron content
03

In context

Obesity

6,296 studies on the registry are indexed under Obesity; 1,695 are open to participants now.

This study's enrollment of 128 is close to the median of 135 across 1,283 observational studies indexed under Obesity.

Browse Obesity studies →

Lead sponsor

Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta is the lead sponsor of 29 studies on the registry; 8 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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.

Inclusion criteria

  1. Men and women aged 30-65 years.
  2. Informed consent for participation in the study.

Exclusion criteria

Exclusion Criteria:

  1. Serious systemic disease unrelated to obesity such as cancer, severe kidney, or liver disease, known type 1 or type 2 diabetes.
  2. Systemic diseases with intrinsic inflammatory activity such as rheumatoid arthritis, Crohn's disease, asthma, chronic infection (e.g., HIV, active tuberculosis) or any type of infectious disease.
  3. Pregnancy and lactation.
  4. Patients with severe disorders of eating behaviour.
  5. Persons whose liberty is under legal or administrative requirement.
  6. Clinical symptoms and signs of infection in the previous month.
  7. Antibiotic, antifungal or antiviral treatment in the previous 3 months.
  8. Anti-inflammatory chronic treatment with steroidal and/or non-steroidal anti-inflammatory drugs.
  9. Major psychiatric antecedents.
  10. Excessive alcohol intake, either acute or chronic (alcohol intake greater than 40 g a day (women) or 80 g/day (men)) or drugs abuse.
  11. Serum liver enzymes (AST, ALT) activity over twice the upper limit of normal.
  12. History of disturbances in iron balance (e.g., genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
05

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
128 participants (actual)
Patient registry
No

Groups and cohorts

  • Premenopausal women with obesity

    Procedure: Bariatric Surgery

  • Postmenopausal women with obesity

    Procedure: Bariatric Surgery

  • Men with obesity

    Procedure: Bariatric Surgery

  • Premenopausal women without obesity
  • Postmenopausal women without obesity
  • Men without obesity

Interventions

  • ProcedureBariatric Surgery

    Subjects with obesity (N=60) will be undertaken a hypocaloric diet and a periodic follow up, also 30 of them will undergo bariatric surgery

06

What researchers measure

Primary outcomes

  1. Concentration of advanced glycation end products (AGE) receptor agonists.

    Enzyme-linked immunosorbent assay (ELISA).

    Time frame: 30 months

  2. Glycemic variability.

    Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.

    Time frame: 30 months

  3. The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)

    Time frame: 30 months

  4. The glycaemic risk measured with low blood glucose index (LBGI)

    Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic excursions in non-negative numbers.

    Time frame: 30 months

  5. The glycaemic risk measured with high blood glucose index (HBGI)

    High blood glucose index (HBGI) is a parameter that quantifies the risk of glycaemic excursions in non-negative numbers.

    Time frame: 30 months

  6. The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE)

    measured in mg/dl

    Time frame: 30 months

  7. Minutes light sleep

    Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.

    Time frame: 30 months

  8. Minutes deep sleep

    Mean and standard deviation of minutes deep sleep measures by activity and sleep tracker device.

    Time frame: 30 months

  9. Minutes rapid eye movement (REM)

    Mean and standard deviation of minutes REM measures by activity and sleep tracker device.

    Time frame: 30 months

Secondary outcomes

  1. Effect on brain structure.

    Brain structure will be assessed using magnetic resonance imaging.

    Time frame: 30 months

  2. Effect on gut microbiota.

    Gut microbiota will be analysed by metagenomics and metabolomics.

    Time frame: 30 months

  3. Changes from baseline in circulating concentration of AGE receptor agonists and glycemic variability one year of follow-up after weight loss in association with changes in brain structure and gut microbiota.

    Subjects with obesity will be undertaken conventional treatment or bariatric surgery for weight loss; controls will not undergo any additional measure.

    Time frame: 30 months

  4. Cognitive impairment

    It will be measured by Mini-Examen Cognoscitivo (MEC). Minimum/maximum scale values (0-30), where ≥ 27 is a normal score.

    Time frame: 30 months

  5. 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: 30 months

  6. 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: 30 months

  7. 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: 30 months

  8. 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: 30 months

  9. 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: 30 months

  10. 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: 30 months

  11. 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: 30 months

  12. 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: 30 months

  13. Visuospatial perception

    It will be measured by Judgment Line Orientation

    Time frame: 30 months

  14. Naming

    It will be measured by Boston Naming Test.

    Time frame: 30 months

  15. Selective and alternating attention

    It will be measured by Trail making test (Part A y B).

    Time frame: 30 months

  16. Attention and working memory

    It will be measured by the Digits subtest of Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV).

    Time frame: 30 months

  17. Inhibition

    It will be measured by Stroop Color-Word Test.

    Time frame: 30 months

  18. Phonemic verbal fluency

    It will be measured by PMR

    Time frame: 30 months

  19. 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: 30 months

  20. 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: 30 months

  21. Brain iron accumulation

    It will be assessed using magnetic resonance imaging using (R2\*)

    Time frame: 30 months

  22. 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: 30 months

  23. Insulin resistance

    It will be measured by HOMA

    Time frame: 30 months

  24. 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: 30 months

  25. Glycosylated hemoglobin (HbA1c) value

    Glycosylated hemoglobin (HbA1c) in % or mmol/mol

    Time frame: 30 months

  26. The percentage of time in hyperglycaemia (glucose level above 250 mg/dl)

    Time frame: 30 months

  27. The percentage of time in hypoglycaemia (glucose level below 70mg/dl)

    Time frame: 30 months

  28. The percentage of time in glucose range (glucose level below 100 mg/dl)

    Time frame: 30 months

  29. The percentage of time in glucose range (glucose level between 126-139 mg/dl)

    Time frame: 30 months

  30. The percentage of time in glucose range (glucose level between 140-199 mg/dl)

    Time frame: 30 months

  31. The percentage of time in glucose range (glucose level above 200 mg/dl)

    Time frame: 30 months

  32. Burned calories

    Mean and standard deviation of burned calories measures by activity and sleep tracker device.

    Time frame: 30 months

  33. Steps

    Mean and standard deviation of steps measures by activity and sleep tracker device.

    Time frame: 30 months

  34. Distance

    Mean and standard deviation of distance measures by activity and sleep tracker device.

    Time frame: 30 months

  35. Minutes null activity

    Mean and standard deviation of minutes null activity measures by activity and sleep tracker device.

    Time frame: 30 months

  36. Minutes slight activity

    Mean and standard deviation of minutes slight activity measures by activity and sleep tracker device.

    Time frame: 30 months

  37. Minutes mean activity

    Mean and standard deviation of minutes mean activity measures by activity and sleep tracker device.

    Time frame: 30 months

  38. Minutes high activity

    Mean and standard deviation of minutes high activity measures by activity and sleep tracker device.

    Time frame: 30 months

  39. Calories

    Mean and standard deviation of calories measures by activity and sleep tracker device.

    Time frame: 30 months

  40. Minutes asleep

    Mean and standard deviation of minutes asleep measures by activity and sleep tracker device.

    Time frame: 30 months

  41. Minutes awake

    Mean and standard deviation of minutes awake measures by activity and sleep tracker device.

    Time frame: 30 months

  42. Bed time

    Mean and standard deviation of bed time measures by activity and sleep tracker device.

    Time frame: 30 months

  43. Number time awake

    Mean and standard deviation of number time awake measures by activity and sleep tracker device.

    Time frame: 30 months

07

Study locations

1 site
  • Institut d'Investigació Biomèdica de Girona (IDIBGI)
    Girona, Girona 17007, Spain
08

References and documents

Publications

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  • Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, Ben-Yacov O, Lador D, Avnit-Sagi T, Lotan-Pompan M, Suez J, Mahdi JA, Matot E, Malka G, Kosower N, Rein M, Zilberman-Schapira G, Dohnalova L, Pevsner-Fischer M, Bikovsky R, Halpern Z, Elinav E, Segal E. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015 Nov 19;163(5):1079-1094. doi: 10.1016/j.cell.2015.11.001. PubMed 26590418 ↗
  • Quince C, Walker AW, Simpson JT, Loman NJ, Segata N. Corrigendum: Shotgun metagenomics, from sampling to analysis. Nat Biotechnol. 2017 Dec 8;35(12):1211. doi: 10.1038/nbt1217-1211b. PubMed 29220029 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 31, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03889132
Lead sponsor
Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
Responsible party
José Manuel Fernández-Real (Principal investigator, clinical professor, section chief of Endocrinology and Nutrition Department of Josep Trueta University Hospital, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta) — Principal investigator
First posted
Mar 26, 2019
Start date
Mar 5, 2019
Primary completion
Jul 31, 2022
Completion
May 31, 2025
Last update
Mar 31, 2026

Study contacts

José Manuel Fernández-Real, M.D., Ph.D.
principal investigator · Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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