NCT06389175

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

Keeping Mind and Body in Sync: Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression

• Status: Enrolling By Invitation
• Phase: N/A
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: University of Bonn · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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.

Conditions

• Depressive Disorder, Major

Interventions

Type	Name	Description
DEVICE	Transcutaneous non-invasive vagus nerve stimulation (tVNS)	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).
DEVICE	Sham stimulation	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).

Timeline

• Start date: 2024-05-21
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2024-04-29
• Last updated: 2024-12-04

Locations

1 site across 1 country: Germany