Role of the Blood-Brain Barrier in Stress Resilience: Investigating New Pathways Towards Pharmacological Augmentation of Stress Resilience

Launched by LEIBNIZ-INSTITUT FÜR RESILIENZFORSCHUNG (LIR) GGMBH · May 2, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring how the blood-brain barrier (BBB) might affect our ability to handle stress and whether a medication called Metformin can help improve the BBB's function. The researchers want to find out if a stronger BBB is linked to better stress resilience, both in the short term and long term. They will focus on young adults aged 18 to 25 who are university students and have experienced significant life stressors but do not have any diagnosed mental health disorders.

Participants in the study will complete online surveys about their stress and mental health every four weeks for 36 weeks. They will also visit the study site four times for health checks, blood samples, and brain scans. During one part of the study, participants will take either Metformin or a placebo (a dummy pill that does nothing) to see if it helps improve BBB function and, in turn, stress resilience. It's important to note that those who have a history of severe mental disorders, brain injuries, or certain health conditions will not be eligible to participate.

Gender

ALL

Eligibility criteria

• • Inclusion criteria: (participants meeting all of the following criteria will be considered for enrollment in the study)
• • 1. Absence of mental disorder diagnosis.
• • 2. University students.
• • 3. GHQ-28 \> 20
• • 4. Three or more adverse life events acc. to LE list in the past
• • 5. Beck Depression Inventory (BDI) ≤ 14 \& Columbia-Suicide Severity Rating Scale (C-SSRS) ≤ 1. Thereby concurrent depression and suicidality are excluded.
• • 6. Age 18 to 25 years
• • 7. Ability of participant to understand character and individual consequences of the study (MMSE Folstein \> 28)
• • 8. Signed and dated informed consent of participant
• • Exclusion criteria: (participants presenting 1 of the following criteria will not be enrolled in the study)
• • 1. Life-time and current diagnosis of any severe mental disorder determined by M.I.N.I. diagnostic interview.
• • 2. Known history of brain injuries or neurodevelopmental disorder.
• • 3. Evidence of neurodegenerative disorder (e.g., Parkinson).
• • 4. Multimorbidity or significant organ (esp. liver or renal) dysfunction or manifest diabetes or substance abuse (esp. alcohol).
• • 5. Contraindication to metformin such as renal insufficiency (Creatinin-Clearance\< 60ml/min), recent (\<3 month) ischemic events (e.g. myocardial infarction or stroke).
• • 6. Women of childbearing age, who do not practice a medically accepted contraception (i.e., systematic contraceptives, diaphragm, condoms with spermicide, sexual abstinence) during the study and during a 2 years post-study period and who do not present a negative pregnancy test (serum or urine).
• • 7. History of hypersensitivity to the study drug, to any drug with similar chemical structure, or to any excipient present in the pharmaceutical form of the study drug.
• • 8. Diabetes type 2 (would result in interference with the experimental manipulation)
• • 9. Participation in other studies employing a drug during the present study or within the last three months.
• • 10. Current use of antidiabetic, weight-loss, or psychoactive medication or substances.
• • 11. Pacemaker, implanted medical pumps, implanted cardiac catheters or acute or unstable heart disease (angina pectoris).
• • 12. Intracranial implant (aneurysm clips, shunts, stimulators, cochlear implants or electrodes) or other metallic objects inside or near the head (mouth excluded) that cannot be removed.
• • 13. Claustrophobia or another contraindication to MRI.
• • 14. Insufficient German language skills.