tVNS and Obesity-related Mechanisms

NCT06954844 · tracked via the Priya Life Science Germany tracker

Sponsor

University of Bonn

Phase

Not applicable

Started

2025-04-08

Last updated

2025-05-02

Condition(s) studied

Overweight/Obesity (BMI: 27 and 35 kg/m2)

Investigational drug(s) / intervention(s)

Transcutaneous non-invasive vagus nerve stimulation (tVNS)Low intensity stimulation

Transcutaneous non-invasive vagus nerve stimulation (tVNS): To stimulate vagal afferents, the electrode will be placed at the cymba conchae of the right ear using a previously established conventional stimulation protocol (30 s ON, 30s OFF, 25 Hz frequency, 250 µs pulse widths; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany). Stimulation intensity will be pre-set for each participant for the following stimulation period to correspond to a mild pricking sensation determined with a staircase procedure in the lab session.

Low intensity stimulation: The electrode will be placed at the cymba conchae, but only receive a low-intensity stimulation below the perception threshold (0.1mA, 1s ON, 30s OFF, 1 Hz frequency, 250 µs pulse widths; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany).

Study summary

The overarching goal of the project is to assess whether transcutaneous Vagus Nerve Stimulation (tVNS) induced reduction of central and peripheral inflammation is associated with tVNS induced changes in mood and motivation in a sample of healthy participants with overweight and obesity.

Eligibility

Sex

ALL

Min age

18 Years

Max age

40 Years

Healthy volunteers

Accepted

Inclusion Criteria: * Between 18 and 40 years of age * BMI between 27 and 35.0 kg/m2 * Legally valid declaration of consent Exclusion Criteria: * Current or past diagnosis of brain injury/surgery or neurological condition with permanent effects, epilepsy, stroke, schizophrenia, bipolar disorder, severe substance use disorder, heart disease that precludes use of tVNS, diabetes (type 1 or 2), chronic inflammatory diseases (e.g., rheumatoid arthritis, Crohn's disease, etc.) * Following diagnosis within 12 months before start of experiment: obsessive compulsive disorder, somatic symptom disorder, eating disorder * Considerable weight change (\>10%) within the last 6 months before the experiment * Elevated BMI is due to fat-free mass (e.g., in athletes) * Medication or Electroconvulsive therapy to treat a mental, metabolic, or neurological disorder (e.g., selective serotonin reuptake inhibitors, Glucagon-like Peptide-1 agonists) currently or in the last 3 months (hormone treatments that normalize function are not excluded) * Anti-inflammatory medication currently or in the last 3 month * Contraindications for MRI (e.g., metal implants, claustrophobia) * Contraindications for tVNS (e.g., piercings, sore or diseased skin areas on the outer right ear) * active implants (e.g., pacemaker), cerebral shunt * Pregnant and breastfeeding women

Primary outcome measure(s)

Stimulation-induced mid-term changes in a multiplex panel of different inflammatory biomarkers (peripheral inflammation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
To measure peripheral inflammation, the investigators will assess plasma levels of pro- and anti-inflammatory cytokines, chemokines, and other biomarker of inflammation (e.g. Growth Factors) using highly sensitive immunoassays (e.g. NULISA). The investigators will select the specific panel after data collection is complete and before data analysis begins, based on the literature and the analysis methods available at that time. Blood levels will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Multivariate analysis will be used to compare stimulation-induced changes in plasma levels between high and low intensity stimulation.
Stimulation-induced mid-term changes in circulating immune cells (peripheral inflammation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
To measure peripheral inflammation, the investigators will measure the following circulating immune cells using fluorescence flow cytometry: Leukocytes, lymphocytes, neutrophil granulocytes, T-cells, (Cluster of Differentiation (CD)4+, CD8+), naïve T cells (CD4+, CD8+), central memory T-cells (CD4+, CD8+), effector memory T-cells (CD4+, CD8+), terminal effector memory re-expressing CD45RA T cells, regulatory T cells (Treg) (activated, resting), conventional T cells, cytotoxic T-cells, T helper cells (Th), Th1 cells, Th2 cells, Th1/17 cells, Th17 cells, effector T-cells, mononuclear phagocytes, monocytes (classical, Intermediate, non-classical), dendritic cells (type 1 conventional, type 2 conventional, plasmacytoid). Cells will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Multivariate analysis will be used to compare stimulation-induced changes in circulating immune cells between high and low intensity stimulation.
Stimulation-induced mid-term changes in tissue edema as assessed using non-restricted fraction (isotropic DBSI-NRF (f(D), D = 0.3 - 3.0 μm2/ms)) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
One measure of central inflammation will be the non-restricted fraction in the brain. This will be calculated with diffusion tensor imaging (DTI) measurement acquired with a 3 Tesla (3T) Siemens Scanner. Non-restricted fraction is calculated as the isotropic DBSI-NRF (f(D), D = 0.3 - 3.0 μm2/ms) and indicates tissue edema. Regions of interest (ROI) will be defined using the Harvard Oxford extended Atlas and include the putamen, caudate, pallidum, and nucleus accumbens (NAcc) as well as the hypothalamus. Non-restricted fraction will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each) and compared in predefined ROIs between high and low intensity stimulation.
Stimulation-induced mid-term changes in tissue cellularity as assessed using restricted fraction (isotropic DBSI-RF (f(D), D ≤ 0.3 μm2/ms)) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
Another measure of central inflammation will be restricted fraction indicating tissue cellularity. This will be calculated with diffusion tensor imaging (DTI) measurement acquired with a 3T Siemens Scanner. Restricted fraction will be calculated as the isotropic DBSI-RF (f(D), D ≤ 0.3 μm2/ms) and indicates tissue edema. Regions of interest (ROI) will be defined using the Harvard Oxford extended Atlas and include the putamen, caudate, pallidum, and NAcc as well as the hypothalamus. Restricted fraction will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each) and compared in predefined ROIs between high and low intensity stimulation.
Stimulation-induced mid-term changes in PANAS items (mood) — Baseline (immediately before each stimulation phase), immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
To measure mood, the investigators will use items from the PANAS, rated on visual analogue scales (VAS) ranging from 0 (lowest rating) to 100 (highest rating). These items will be assessed at baseline (before each stimulation phase) and after each stimulation phase (high and low intensity; 14 days stimulation each). Values from the Positive and Negative Affect Schedule will be analysed as repeated measures assessing either positive (PA) or negative (NA) affect. Stimulation-induced changes in mood state (PA - NA) will be compared between high and low intensity stimulation.
Stimulation-induced mid-term changes in Invigoration (motivation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
Invigoration will be assessed using the effort allocation task and is captured by the slope of the initial approach (i.e., the increase of force until a first plateau is reached). Invigoration will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Stimulation-induced changes in Invigoration will be compared between high and low intensity stimulation.
Stimulation-induced mid-term changes in maintenance (motivation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
Maintenance will be assessed using the effort allocation task and reflects the average relative force/frequency across the whole trial. Maintenance will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Stimulation-induced changes in maintenance will be compared between high and low intensity stimulation.
Stimulation-induced mid-term changes in anticipatory neural reward response (motivation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
To evaluate anticipatory neural reward response, the investigators will assess fMRI bold signals during cue presentation prior to exerting effort during the effort allocation task using a 3T Siemens Scanner. The contrast of interest will be the modulation of the anticipatory response by the reward magnitude (high vs. low) combining responses to food and monetary rewards. Other contrasts (cue response itself and contrasts specific for food or monetary rewards are exploratory). Regions of Interest (ROI) will be defined using the Harvard Oxford extended Atlas. Primary ROIs will be the NAcc and ventromedial prefrontal cortex (vmPFC) and secondary ROIs will be ventral tegmental area (VTA)/substantia nigra (SN), and caudate, and putamen. fMRI metrics will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Stimulation-induced changes in bold signals in predefined ROI will be compared between high and low intensity stimulation.
Stimulation-induced mid-term changes in neural motor response (motivation) — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
To evaluate neural motor response, the investigators will assess fMRI bold signals while the participants exert effort (work phase) during the effort allocation task using a 3T Siemens Scanner. The contrasts of interest will be force/repetition time (TR) to assess motor work during the task and the first derivative of force/TR (temporal relative = d(force)/d(TR)) estimating the drive to work. Region of Interest (ROI) will be defined using the Harvard Oxford extended Atlas and include the supplementary motor area (SMA) and pre-SMA, as well as VTA/SN, and caudate, putamen, and NAcc. fMRI metrics will be assessed at baseline and after each stimulation phase (high and low intensity; 14 days stimulation each). Stimulation-induced changes in bold signals in predefined ROI will be compared between high and low intensity stimulation.
Correlation of Stimulation-induced changes in peripheral and central inflammation with changes in mood and motivation — Baseline, immediately after the first 14-day stimulation phase and before a 7-day washout, immediately after the second 14-day stimulation phase
The investigators will correlate changes (i.e., random effect estimates of high intensity stimulation slopes relative to low intensity stimulation) in peripheral and central inflammation markers with tVNS-induced (high vs. low intensity) changes in mood and motivation.

Trial sites (1)

Facility	City	Region	Status
Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn	Bonn	Germany

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

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