Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression

NCT06389175 | Enrolling By Invitation

• 2 other identifiers: BON001KR 4555/10-1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Depressive Disorder, Major

Keywords

major depressive disorder; stomach-brain coupling; tVNS

Outcome Measures

Primary Outcomes (10)

• Stimulation-induced acute changes in stomach-brain coupling

  Stomach-brain coupling will be assessed using phase-locking values (PLV) at baseline and during tVNS/sham stimulation concurrent to electrogastrogram (EGG) measurements in the MRI. PLV will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham) with a focus on core regions of the gastric network (postcentral gyrus, cingulate gyrus, precuneus, occipital cortex, fusiform gyrus, inferior frontal gyrus, inferior and superior parietal lobe, thalamus, and inferior cerebellum) and the vagal afferent pathway (nucleus of the solitary tract (NTS), ventral tegmental area (VTA), substantia nigra, hypothalamus, amygdala, putamen, caudate, nucleus accumbens, hippocampus, insula, ventromedial prefrontal cortex, lateral orbitofrontal cortex, dorsal anterior cingulate cortex). PLV will be correlated with self-reported interoception, somatic symptoms, and depressive symptoms (see below).

  During MRI scan (up to 120 minutes)

• Stimulation-induced acute changes in gastric motility

  The gastric myoelectric frequency will be assessed during the MRI sessions at baseline and during tVNS and sham stimulation using an EGG. Acute changes in gastric peak frequency will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  During MRI scan (up to 120 minutes)

• Stimulation-induced mid-term changes in gastric motility

  The gastric myoelectric frequency will be assessed at the beginning and end of the extended stimulation periods using an EGG. Data will be collected at baseline and during tVNS and sham stimulation and mid-term changes in gastric peak frequency from the beginning to the end of the extended stimulation periods will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced mid-term changes in self-reported interoception

  Interoception is assessed by using the Multidimensional Assessment of Interoceptive Awareness questionnaire, version 2 (MAIA-2). Changes in awareness of bodily sensations will be assessed from the beginning to the end of the extended stimulation period and compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced mid-term changes in somatic symptoms

  The Patient Health Questionnaire-15 (PHQ-15) will be used as self-report measurements to assess changes in severity of somatic symptoms from the beginning to the end of the extended stimulation periods. Changes across time will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced mid-term changes in depressive symptoms

  The Beck's Depression Inventory (BDI-II) will be used to assess changes in depressive symptoms from the beginning to the end of the extended stimulation periods. Changes across time will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced acute neural changes in food cue reactivity

  Brain activity (BOLD signal) in response to food stimuli (contrasted with office supplies) and during exerting effort on a grip force device will be analyzed by focusing on brain regions associated with the vagal afferent pathway. Brain activity will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  During MRI scan of a food bidding task (~13 minutes)

• Stimulation-induced acute behavioral changes in invigoration

  Invigoration related to food stimuli (contrasted with office supplies) will be operationalized via the relative effort exerted on a grip force device. Invigoration will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  During MRI scan of a food bidding task (~13 minutes)

• Stimulation-induced acute neural changes during foraging

  Brain activity (BOLD signal) during a foraging task will be analyzed by focusing on brain regions associated with the vagal afferent pathway. Brain activity will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).

  During MRI scan of a foraging task (~25 minutes)

• Stimulation-induced acute behavioral changes in foraging decisions

  Decisions to accept or reject an offered option during a foraging task will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham). Analyses will focus on acceptance rates during different environments (poor and rich environment) for options differing in the effort needed to accept the option and the earned outcome and learning parameters based on trial-to-trial choices.

  During MRI scan of a foraging task (~25 minutes)

Secondary Outcomes (8)

• Stimulation-induced mid-term changes in positive and negative affect

  During extended stimulation period (up to approx. 2 weeks)

• Stimulation-induced mid-term changes in self-reported interoception

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced mid-term changes in motivation

  Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period)

• Stimulation-induced mid-term changes in physical activity

  During extended stimulation period (up to approx. 2 weeks)

• Stimulation-induced mid-term changes in heart rate

  During extended stimulation period (up to approx. 2 weeks)

Other Outcomes (4)

• Stimulation-induced mid-term changes in discounting-related decision-making

  During extended stimulation period (up to approx. 2 weeks)

• Stimulation-induced mid-term changes in reward learning

  During extended stimulation period (up to approx. 2 weeks)

• Stimulation-induced mid-term changes in loneliness

  During extended stimulation period (up to approx. 2 weeks)

Study Arms (2)

Patients suffering from MDD

EXPERIMENTAL

All participants will receive tVNS and sham stimulation in a randomized order.

Device: Transcutaneous non-invasive vagus nerve stimulation (tVNS); Device: Sham stimulation

Healthy controls (HC)

EXPERIMENTAL

All participants will receive tVNS and sham stimulation in a randomized order.

Device: Transcutaneous non-invasive vagus nerve stimulation (tVNS); Device: Sham stimulation

Interventions

Transcutaneous non-invasive vagus nerve stimulation (tVNS) DEVICE

Participants receive tVNS during the neuroimaging sessions and the extended stimulation period. To stimulate vagal afferents, the electrode will be placed at the cymba conchae of the right ear using a previously established, conventional stimulation protocol (25 Hz, 30s on/30s off cycle; NEMOS device, Cerbomed, Erlangen, Germany). To improve blinding, the stimulations intensities will be adjusted to correspond to a mild pricking sensation for tVNS and sham. The extended stimulation period in the experimental group involves six sessions with at least 1.5h of stimulation (stimulation in the lab or at home with home device using the same stimulation protocol as during the neuroimaging sessions; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany).

Healthy controls (HC); Patients suffering from MDD

Sham stimulation DEVICE

The control intervention consists of a sham stimulation. In the neuroimaging session the electrode will be placed upside down to stimulate the earlobe, which is not innervated by vagal afferent fibers. To improve blinding, the same stimulation protocol as for the tVNS will be applied (25 Hz, 30s on/30s off cycle; NEMOS device, Cerbomed, Erlangen, Germany) and stimulation intensities will be adjusted to correspond to a mild pricking sensation. During the extended stimulation period, the electrode will be placed at the cymba conchae, but only receive a low-intensity stimulation below the perception threshold (0.1mA). To ensure blinding, participants will be instructed that the extended stimulation period will examine the effects of a low- vs. high-intensity tVNS protocol. Each repeated stimulation period will involve six sessions with at least 1.5h of low-intensity stimulation (stimulation in the lab or at home with home device; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany).

Healthy controls (HC); Patients suffering from MDD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Bonn: lead
• University Hospital Tuebingen: collaborator

Study Sites (1)

Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn

Bonn, 53127, Germany

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Nils B Kroemer, Prof.

  Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn, 53127 Bonn, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. rer. nat.

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: May 21, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will become available after an embargo period of 12 months after completion of the study
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access.

Locations

DE (1)