Improving cognition in elderly patients with Type 2 Diabetes through gut microbiome modification

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

This study is testing whether metformin can improve thinking skills and gut health in older adults with Type 2 Diabetes.

Quick facts

• Study type: Observational
• Enrollment: 136 (estimated)
• Ages: 65 Years to 80 Years
• Sex: All
• Sponsor: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (Academic / other)
• Locations: 1 site (Girona)
• Trial ID: NCT04841668 on ClinicalTrials.gov

What this trial studies

This observational study investigates the impact of metformin on cognitive function and gut microbiota composition in elderly patients with Type 2 Diabetes Mellitus (T2DM). Participants will be monitored over a year, with an initial phase of dietary management followed by metformin treatment. Continuous glucose monitoring and physical activity tracking will be employed to assess the relationship between glucose levels, cognitive performance, and microbiome changes. The study aims to provide insights into how metabolic interventions can influence cognitive health in this population.

Who should consider this trial

Good fit: Ideal candidates are elderly individuals aged 55 to 80 years with a recent diagnosis of Type 2 Diabetes Mellitus.

Not a fit: Patients with severe systemic diseases, significant kidney issues, or those currently on metformin may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved cognitive function in elderly patients with Type 2 Diabetes through targeted dietary and pharmacological interventions.

How similar studies have performed: While the specific approach of this study is novel, previous studies have indicated potential benefits of gut microbiome modulation in metabolic and cognitive health.

Eligibility criteria

Group A

Inclusion Criteria:

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

Exclusion Criteria:

1. HbA1c ≥ 9%
2. Metformin treatment in the past 6 months
3. Creatinine greater than 1.2 and glomerular filtration rate less than 40
4. Serious systemic disease not related to obesity, including any type of cancer, severe kidney disease or liver disease, and known type 1 diabetes.
5. 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.
6. Current treatment for malignant neoplasia, other than basal cell or squamous cell skin cancer.
7. Class III or IV heart disease, known ischemic cardiovascular disease
8. Kidney failure, history of kidney transplant, or current dialysis treatment
9. Serum liver enzymes (GOT, GPT) above twice the upper limit of normal. Obvious signs or symptoms of liver disease, acute or chronic hepatitis.
10. Chronic constipation (stool habit ≥ 7 days)
11. Pregnancy or breastfeeding
12. 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.
13. Chronic anti-inflammatory treatment with steroidal drugs (during the previous 3 months).
14. Symptoms and / or clinical signs of infection in the previous month.
15. Antibiotic, antifungal or antiviral treatment active in the previous 3 months.
16. Treatment with glucocorticoids chronic or during the 2 months prior to inclusion in the study.
17. Treatment with a weight loss product during the previous two months
18. Immunosuppressant treatment.
19. Excessive alcohol consumption (alcohol intake greater than 40 g per day (women) or 80 g / day (men)) either acute or chronic, or drug use. History of drug or alcohol abuse.
20. Patients with severe eating disorders
21. History of alterations in iron balance (known chronic hemoglobinopathies or anemia, genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
22. Important psychiatric history.
23. Participation in any other study.
24. People whose freedom is under legal or administrative requirement.

Group B

Inclusion Criteria:

1. Age between 65 and 80 years.
2. Patients with long-term T2DM according to the WHO classification
3. Patients in whom written informed consent has been obtained for participation in the study.

Exclusion Criteria:

1. HbA1c ≥ 9%
2. Creatinine greater than 1.2 and glomerular filtration rate less than 40
3. Serious systemic disease not related to obesity, including any type of cancer, severe kidney disease or liver disease, and known type 1 diabetes.
4. 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.
5. Current treatment for malignant neoplasia, other than basal cell or squamous cell skin cancer.
6. Class III or IV heart disease, known ischemic cardiovascular disease.
7. Kidney failure, history of kidney transplant, or current dialysis treatment
8. Serum liver enzymes (GOT, GPT) above twice the upper limit of normal. Obvious signs or symptoms of liver disease, acute or chronic hepatitis.
9. Chronic constipation (stool habit ≥ 7 days)
10. Pregnancy or breastfeeding
11. Chronic anti-inflammatory treatment with steroidal drugs (during the previous 3 months).
12. Symptoms and / or clinical signs of infection in the previous month.
13. Antibiotic, antifungal or antiviral treatment active in the previous 3 months.
14. Treatment with glucocorticoids chronic or during the 2 months prior to inclusion in the study.
15. Treatment with a weight loss product during the previous two months.
16. Immunosuppressant treatment.
17. Excessive alcohol consumption (alcohol intake greater than 40 g per day (women) or 80 g / day (men)) either acute or chronic, or drug use. History of drug or alcohol abuse.
18. Patients with severe eating disorders
19. History of alterations in iron balance (known chronic hemoglobinopathies or anemia, genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
20. Important psychiatric history.
21. Participation in any other study.
22. People whose freedom is under legal or administrative requirement.

Where this trial is running

Girona

• Institut d'Investigació Biomèdica de Girona (IDIBGI) — Girona, Spain (Recruiting)

Study contacts

• Principal investigator: José M Fernández-Real, Ph.D. — Institut d'Investigació Biomèdica de Girona (IDIBGI)
• Study coordinator: José M. Fernández-Real, Ph.D.

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