Stress resilience and mental health under metabolic modulation in healthy adults
Conditions
Interventions
Group 1: This is a monocentric, randomized, double-blind, controlled crossover trial with two study arms. Each participant completes both interventions on two separate study days, with the order rando
Sponsors
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: - Healthy adults from the LORA cohort - Clinically unremarkable medical history - Capacity to give informed consent, able to understand the nature and individual implications of the research study
Exclusion criteria
Exclusion criteria: - Currently or within the last 6 months following a low-carbohydrate or ketogenic diet - Diabetes or other metabolic disorders - Regular use of psychotropic medications or recreational drugs - Cardiovascular diseases - Blood clotting disorders - Skin conditions on the hands - Body mass index (BMI) 29.9 (obesity) - Participation in high-performance sports - Potential pregnancy - MRI contraindications - Insufficient proficiency in German - Lifetime diagnosis of a severe psychiatric disorder - Known history of alcohol, drug, or medication abuse or dependence - Known history of brain injury or neurological developmental disorders, or presence of a neurological disease - Other serious health problems or current severe mental or physical stress - Participation in other clinical drug trials during the present study or within the last three months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| WHAT: Change in resting-state brain network stability following acute metabolic intervention. WHEN: At two time points on each study visit: T0 (Baseline): prior to administration of the study intervention T1: 30 minutes after ingestion of ß-hydroxybutyrate (BHB) or the calorically matched glucose solution HOW: Brain network stability is assessed using resting-state functional magnetic resonance imaging (rs-fMRI) and quantified with a dynamic functional connectivity approach. Network stability metrics are derived according to the method described by Mujica-Parodi et al. (2020, PNAS), which captures the temporal stability of large-scale functional brain networks. The primary endpoint is the within-subject difference in network stability between the BHB and glucose conditions (crossover design), testing acute metabolic effects and their robustness in an independent sample of healthy adults. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint 1a: Association between resilience and brain network stability (baseline) WHAT: Association between outcome-based resilience and resting-state brain network stability. WHEN: Baseline (T0) on each study visit, prior to intervention intake. HOW: Resilience is operationalized using stressor reactivity (SR) scores derived from the Longitudinal Resilience Assessment (LORA) cohort. Brain network stability is assessed using resting-state functional MRI (rs-fMRI) and a dynamic functional connectivity approach as described by Mujica-Parodi et al. (2020, PNAS) Cross-sectional associations between SR scores and network stability are analyzed. Secondary Endpoint 1b: Association between resilience and blood–brain barrier integrity (baseline) WHAT: Association between outcome-based resilience and blood–brain barrier (BBB) permeability. WHEN: Baseline (T0) on each study visit, prior to intervention intake. HOW: Resilience is measured using SR scores. BBB integrity is assessed using arterial spin labeling (ASL) MRI; water exchange rate (kw) serves as the quantitative marker of BBB permeability. Lower kw values indicate greater BBB integrity. Cross-sectional associations between SR scores and BBB permeability are examined. Secondary Endpoint 2: Resilience as a moderator of acute metabolic effects WHAT: Moderating effect of resilience on the acute effects of ß-hydroxybutyrate (BHB) versus glucose on brain network stability. WHEN: On both study visits at: - T0: baseline before ingestion - T1: 30 minutes after ingestion of BHB or glucose HOW: Resilience is quantified using SR scores. Brain network stability is measured via rs-fMRI and dynamic functional connectivity analysis. Moderation is tested statistically by examining the interaction between resilience and intervention condition on changes in network stability. Secondary Endpoint 3: Test–retest reliability WHAT: Test–retest reliability of - resting-state brain netwo | — |
Countries
Germany
Contacts
Public ContactAlexandra Sebastian
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Outcome results
None listed