Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly

NCT04841668 | Completed

• 1 other identifier: SMARTAGE-2020.133
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive disorders increase with age and in the presence of metabolic diseases such as Type 2 Diabetes Mellitus (T2DM). In addition, digestive disorders, changes in dietary pattern and decreased activity negatively influence the microbiome. The hypothesis is that pharmacological intervention with metformin will modify the composition of the gut microbiota and cognition. The study has a pilot longitudinal design, where each patient with T2DM will be followed for one year. Two groups will be recruited:

1. 1.Group A: The aim will be to evaluate the associations between glucose (measured by continuous glucose monitoring (CGM)), cognitive function (by means of cognitive tests and magnetic resonance imaging (MRI)), physical activity (recorded by activity and sleep tracker devicer), metformin, diet (evaluated by nutritional survey) and composition of the microbiota (evaluated by metagenomics), during 12 months (6 months without metformin and 6 months with metformin treatment).
2. 2.Group B: The aim will be to evaluate the associations between glucose, diet (evaluated by nutritional survey), cognitive function (by means of cognitive tests), physical activity (measured by activity and sleep tracker device), the treatment and composition of the microbiota (evaluated by metagenomics), during 12 months.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Continous Glucose Monitoring; Cognition; Metformin; Gut microbiome; Magnetic resonance imaging; Physical activity monitor

Outcome Measures

Primary Outcomes (17)

• Gut microbiota composition.

  It will be identified in the stool by cultures and DNA and mRNA expression after metformin treatment.

  12 months

• Cognitive impairment

  It will be measured by Mini-Examen Cognoscitivo (MEC).

  12 months

• Audioverbal memory

  It will be measured by Test aprendizaje verbal-TAVEC.

  12 months

• Visual memory

  It will be measured by Rey-Osterrieth Complex Figure.

  12 months

• Depressive symptomatology

  It will be measured by Patient Health Questionnaire-9 (PHQ-9).

  12 months

• Impulsivity

  It will be measured by UPPS Impulsive Behavior Scale.

  12 months

• Food Addiction

  It will be measured by Yale Food Addiction Scale.

  12 months

• Behavioral inhibition

  It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ).

  12 months

• Behavioral activation

  It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ).

  12 months

• Visoconstructive function

  It will be measured by Rey-Osterrieth Complex Figure.

  12 months

• Visuospatial perception

  It will be measured by Judgment Line Orientation.

  12 months

• Naming

  It will be measured by Boston Naming Test.

  12 months

• Selective and alternating attention

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

  12 months

• Attention and working memory

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

  12 months

• Inhibition

  It will be measured by Stroop Color-Word Test.

  12 months

• Phonemic verbal fluency

  It will be measured by PMR

  12 months

• Semantic verbal fluency

  It will be measured by Animals

  12 months

Secondary Outcomes (6)

• The percentage of time in glucose target range (glucose level 70mg/dl-180mg/dl)

  12 months

• Effect on gut microbiota

  12 months

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

  12 months

• The percentage of time in glucose range (glucose level between 100-125 mg/dl)

  12 months

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

  12 months

Other Outcomes (28)

• Integrity of the brain gray matter

  12 months

• Integrity of the white matter tracts

  12 months

• Brain iron accumulation

  12 months

Study Arms (2)

Patients with recently diagnosed T2DM

This group will consist of 36 recently diagnosed T2DM, according to the World Health Organization (WHO) patients (last 6 months), who have not received treatment with metformin.

Drug: Metformin

Patients with long-term T2DM

The group will consist of 100 patients with long-term T2DM, according to the WHO classification, regardless of whether they take metformin or another treatment.

Interventions

Metformin DRUG

Patients will begin treatment with metformin administered orally at a starting dose of 425 mg / day every 12 hours for the first 15 days and then continue with a dose of 850 mg / day until the end of the study. The beginning of this treatment phase will be following the recommendations of the clinical guidelines (Comprehensive Approach to Type 2 Diabetes Mellitus, SEEN V2019.2)

Patients with recently diagnosed T2DM

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Group A Study population Adult patients (≥ 65 years of age) recently diagnosed with T2DM according to the WHO and who have not been treated with metformin. Group B Study population Adult patients (≥ 65 years of age) diagnosed with long-term T2DM according to the WHO classification, regardless of whether they take metformin or other treatment.

You may qualify if:

• Age between 55 and 80 years.
• Patients with recently diagnosed T2DM (last 6 months), according to the WHO classification.
• Patients in whom written informed consent has been obtained for participation in the study.

You may not qualify if:

• HbA1c ≥ 9%
• Metformin treatment in the past 6 months
• Creatinine greater than 1.2 and glomerular filtration rate less than 40
• Serious systemic disease not related to obesity, including any type of cancer, severe kidney disease or liver disease, and known type 1 diabetes.
• Systemic diseases with intrinsic inflammatory activity such as rheumatoid arthritis, Crohn's disease, asthma, or chronic infection (e.g., HIV, active tuberculosis) or any type of infectious disease.
• Current treatment for malignant neoplasia, other than basal cell or squamous cell skin cancer.
• Class III or IV heart disease, known ischemic cardiovascular disease
• Kidney failure, history of kidney transplant, or current dialysis treatment
• Serum liver enzymes (GOT, GPT) above twice the upper limit of normal. Obvious signs or symptoms of liver disease, acute or chronic hepatitis.
• Chronic constipation (stool habit ≥ 7 days)
• Pregnancy or breastfeeding
• Treatments that affect glucose metabolism or the intestinal microbiota with biguanides, sulfonylurea secretagogues or non-sulfonylurea secretagogues, insulin sensitizers, insulin, thiazolidinediones, alpha glucosidase inhibitors, incretin mimetics, Dipeptidyl peptidase IV inhibitors, use of cathartics.
• Chronic anti-inflammatory treatment with steroidal drugs (during the previous 3 months).
• Symptoms and / or clinical signs of infection in the previous month.
• Antibiotic, antifungal or antiviral treatment active in the previous 3 months.

Sponsors & Collaborators

• Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta: lead

Study Sites (1)

Institut d'Investigació Biomèdica de Girona (IDIBGI)

Girona, Girona, 17007, Spain

Location

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• José M Fernández-Real, Ph.D.

  Institut d'Investigació Biomèdica de Girona (IDIBGI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, clinical professor, section chief of Endocrinology and Nutrition Department of Josep Trueta University Hospital

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 12, 2021
• Study Start: April 10, 2021
• Primary Completion: December 3, 2024
• Study Completion: December 3, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

ES (1)