Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression
NCT ID: NCT06389175
Last Updated: 2024-12-04
Study Results
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Basic Information
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ENROLLING_BY_INVITATION
NA
80 participants
INTERVENTIONAL
2024-05-21
2026-12-31
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
SINGLE
Study Groups
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Patients suffering from MDD
All participants will receive tVNS and sham stimulation in a randomized order.
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).
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).
Healthy controls (HC)
All participants will receive tVNS and sham stimulation in a randomized order.
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).
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).
Interventions
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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).
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).
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
55 Years
ALL
Yes
Sponsors
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University Hospital Tuebingen
OTHER
University of Bonn
OTHER
Responsible Party
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Dr. Nils B. Kroemer
Prof. Dr. rer. nat.
Principal Investigators
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Nils B Kroemer, Prof.
Role: PRINCIPAL_INVESTIGATOR
Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn, 53127 Bonn, Germany
Locations
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Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn
Bonn, , Germany
Countries
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Other Identifiers
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KR 4555/10-1
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
BON001
Identifier Type: -
Identifier Source: org_study_id