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

Summary

The goal of this clinical trial is to better understand the relationship between blood-brain barrier (BBB) function and stress resilience and to investigate a potential causal role for BBB function in stress resilience in humans. The researchers will look for particpants that are young adults to answer the following questions to reach our goal:

* Is better BBB integrity, measured with neuroimaging, associated with better stress resilience in the short term and in the long term?
* Does the administration of Metformin improve BBB integrity?
* Is improved BBB integrity a possible link between Metformin and better short- and long-term stress resilience?

The participants will do the following during our study:

* Participants will fill in online surveys on stressor exposure and mental health once every four weeks over 36 weeks
* Participants will visit the study site 4 times:
* The first time for a screening process which includes questionnaires, a medical exam and a blood sample.
* The next 2 visits will include a blood sample, a medical exam, an MRI scan and a list of questionnaires
* The last visit will include another blood sample, a medical exam and a list of questionnaires.
* Between visit 2 and 3, the participant will take either Metformin or Placebo

Conditions

• Stress Resilience
• Blood-Brain Barrier Integrity
• Mental Health

Interventions

DRUG

Metformin

The Metformin intervention will be self-administred capsules, taken during a 12-week period: Four weeks of dose increase; first and second week 500 mg once daily, third and fourth week 500mg twice daily. Full-dose administration (850 mg twice daily) for eight weeks.

DRUG

Placebo

This intervention will be self-administered placebo capsules

Sponsors & Collaborators

• University of Latvia

  collaborator OTHER

• University of Zurich

  collaborator OTHER

• Johannes Gutenberg University Mainz

  collaborator OTHER

• University of Warsaw

  collaborator OTHER

• Leibniz-Institut für Resilienzforschung (LIR) gGmbH

  lead OTHER

Principal Investigators

• Raffael Kalisch, Prof. Dr. · Leibniz Institute for Resilience Research gGmbH (LIR)

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-06-30

Primary Completion

2027-02-28

Completion

2027-02-28

Countries

• Germany
• Poland
• Switzerland

Study Locations