Clinical trial NCT06389175: Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression
Official title: Keeping Mind and Body in Sync: Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Depressive Disorder, Major
Keywords: major depressive disorder
stomach-brain coupling
tVNS
Lead sponsor: University of Bonn
Sponsor class: OTHER
Collaborators: name: University Hospital Tuebingen
First posted: 2024-04-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The overarching goal of the project is to determine whether differences in stomach-brain coupling contribute to key symptoms of major depressive disorder (MDD) and whether transcutaneous non-invasive vagus nerve stimulation (tVNS) may serve as a non-invasive intervention to improve aberrant interoceptive signaling in participants suffering from MDD.

Detailed description: It is planned to conduct a randomized cross-over study including two neuroimaging sessions to assess the effect of acute tVNS (vs. sham) on stomach-brain coupling using concurrent fMRI and EGG. Furthermore, to evaluate potential medium-term effects of repeated applications of tVNS (vs. sham), changes across two weeks in gastric myoelectric frequency and interoception/somatic sensations as well as metabolic and mood states will be evaluated using a combination of lab-based with ecological momentary assessments (EMA).

Consequently, three major hypotheses will be tested:

Hypothesis 1: Participants suffering from MDD show altered stomach-brain coupling compared to matched healthy control participants; inter-individual differences in interoceptive measures/somatic sensations correlate with stomach-brain coupling.

Hypothesis 2: tVNS enhances stomach-brain coupling in a vagal afferent network.

Hypothesis 3: In participants suffering from MDD, tVNS influences interoception/somatic sensations and normalizes gastric myoelectric frequency over an extended stimulation period.

In addition to these main outcomes, tNVS effects on value-based decision-making will be investigated. In detail, participants will be invited to two neuroimaging sessions (T1 and T2) including tVNS or a sham stimulation. At the beginning of each of these sessions, blood will be drawn to determine concentrations of circulating hormones. Afterwards, participants will undergo MRI and complete the following tasks: 1.) Watching an Inscape movie specifically designed to improve imaging at rest. After a 10-minutes baseline scan, tVNS/sham stimulation will start and the Inscape scan is repeated. 2.) Food bidding task to assess neural food cue reactivity as well as bidding behavior and its neural correlates when participants are asked to bid for accessing the presented food. 3.) Foraging task to assess value-based decision-making and its neural correlates with the goal to maximize points in different environments (poor and rich environment). After completing the food bidding and foraging task, the Inscape movie is presented once more to assess tVNS effects after a prolonged stimulation. Throughout all MRI tasks, stomach activity will be assessed by an EGG. Both neuroimaging sessions end with an additional blood draw.

Following the neuroimaging sessions, participants will be invited to two extended stimulation periods (tVNS vs. sham), each lasting approximately two weeks. At the beginning of the extended stimulation periods, participants will be invited to the lab and blood will be drawn (T3). Gastric myoelectric frequency using EGG and value-based decision-making will be assessed at baseline and during stimulation (tVNS or sham). After completing the session, participants are given a tVNS device and are asked to stimulate their vagus nerve for 1.5h at least on four days during the following two weeks. During this time period, participants complete further tasks on value-based decision-making and questionnaires using ecological momentary assessments. In detail, four tasks will cover different aspects of value-based decision making: 1.) Effort allocation task (motivation to work for rewards; completed at T3-T6), 2.) temporal discounting (completed during the whole extended stimulation period), 3.) social discounting (completed during the whole extended stimulation period), and 4.) Influenca (gamified reinforcement learning; completed during the whole extended stimulation period).

After two weeks, participants will again come to the lab and EGG recordings and value-based decision-making tasks will be repeated (T4). Likewise, another blood sample will be collected. The extended stimulation period will then be repeated in the same way for the other stimulation type (tVNS or sham), including both sessions in the lab (T5 and T6). The order of tVNS and sham stimulation is randomized for both neuroimaging sessions as well as the extended stimulation period.

Eligibility criteria: Inclusion Criteria:

* Between 18 and 55 years of age
* BMI between 18.5 and 30kg/m\^2
* Legally valid declaration of consent
* MDD group: current major depressive episode based on DSM V criteria

Exclusion Criteria:

* Current or past diagnosis of brain injury, epilepsy, schizophrenia, bipolar disorder, severe substance use disorder (exception: tobacco), coronary heart disease, stroke
* Following diagnosis within 12 months before start of experiment: obsessive compulsive disorder, somatic symptom disorder, eating disorder
* Contraindications for MRI (e.g. metal implants, claustrophobia) or tVNS (e.g. piercings, sore or diseased skin areas on the outer right ear)
* Pregnant and breastfeeding women are not included
* Unclear ability to give consent

Primary outcomes:
measure: Stimulation-induced acute changes in stomach-brain coupling
timeFrame: During MRI scan (up to 120 minutes)
measure: Stimulation-induced acute changes in gastric motility
timeFrame: During MRI scan (up to 120 minutes)
measure: Stimulation-induced mid-term changes in gastric motility
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in self-reported interoception
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in somatic symptoms
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in depressive symptoms
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced acute neural changes in food cue reactivity
timeFrame: During MRI scan of a food bidding task (~13 minutes)
measure: Stimulation-induced acute behavioral changes in invigoration
timeFrame: During MRI scan of a food bidding task (~13 minutes)
measure: Stimulation-induced acute neural changes during foraging
timeFrame: During MRI scan of a foraging task (~25 minutes)
measure: Stimulation-induced acute behavioral changes in foraging decisions
timeFrame: During MRI scan of a foraging task (~25 minutes)
Secondary outcomes:
measure: Stimulation-induced mid-term changes in positive and negative affect
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced mid-term changes in self-reported interoception
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in motivation
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in physical activity
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced mid-term changes in heart rate
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced acute changes in blood parameters
timeFrame: Before and after stimulation/MRI scan (up to three hours)
measure: Stimulation-induced mid-term changes in blood parameters
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
measure: Stimulation-induced mid-term changes in composition of microbiome
timeFrame: Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)
Other outcomes:
measure: Stimulation-induced mid-term changes in discounting-related decision-making
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced mid-term changes in reward learning
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced mid-term changes in loneliness
timeFrame: During extended stimulation period (up to approx. 2 weeks)
measure: Stimulation-induced mid-term changes in sleep
timeFrame: During extended stimulation period (up to approx. 2 weeks)
Locations:
city: Bonn
country: Germany
facility: Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn
Study officials:
affiliation: Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn, 53127 Bonn, Germany
name: Nils B Kroemer, Prof.
role: PRINCIPAL_INVESTIGATOR
References: