Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation in Depression

Condition(s) studied

Investigational drug(s) / intervention(s)

transcutaneous auricular vagus nerve stimulation: Half of the patients are randomized to the arm receiving transcutaneous auricular vagus nerve stimulation for a period of six weeks. Transcutaneous auricular vagus nerve stimulation will be carried out as an adjuvant, i.e. in addition to the regular treatment of the participants. The intervention will take place three times a day from Monday to Friday. Each of the three daily sessions is going to last 30-60 minutes, depending on patient tolerance.

sham transcutaneous auricular vagus nerve stimulation: Half of the patients are randomized to the arm receiving sham transcutaneous auricular vagus nerve stimulation for a period of six weeks. Sham transcutaneous auricular vagus nerve stimulation will be carried out as an adjuvant, i.e. in addition to the regular treatment of the participants. The intervention will take place three times a day from Monday to Friday. Each of the three daily sessions is going to last 30-60 minutes. The procedures for sham tVNS will be identical to tVNS, with the only exception that the sham tVNS will be performed with no current output

Study summary

Invasive vagus nerve stimulation (VNS) is an approved treatment of treatment-resistant depression (TRD) in Europe and in USA. Because of the associated possible surgical complications as well as side effects, invasive VNS is applied limitedly in the treatment of depression. Transcutaneous auricular VNS (tVNS), on the other hand, is a non-invasive alternative to traditional invasive VNS. tVNS is still considered an experimental treatment for depression. This is due to the limited high-quality evidence from randomized clinical studies, the not yet fully understood biological mechanisms of action, along with overall limited knowledge about the optimal stimulation parameters. To address these issues, the AddVNS study was initiated. The AddVNS study intends to recruit n=86 patients of the Max Planck Institute of Psychiatry with depression. The patients participating in the AddVNS study are going to receive either tVNS or sham tVNS for a period of 6 weeks. The primary objective of the study is to identify biological, psychological, socio-economic, and clinical biomarkers associated with treatment progression and response to treatment in patients with depression undergoing tVNS. To achieve this, an exploratory design with an assessment of many different parameters including psychophysiology, imaging, blood-based multi-omics, microbiome, psychometrics and neuropsychology will be used.

Eligibility

Primary outcome measure(s)

• Change from baseline in pupillometry — Baseline, week 3, week 6
  Pupil diameter associated with the clinical response to tVNS
• Change from baseline in 3-channel ECG — Baseline, week 3, week 6
  3-channel ECG associated with the clinical response to tVNS
• Change from baseline in skin conductance level — Baseline, week 3, week 6
  Skin conductance level associated with the clinical response to tVNS
• Change from baseline in photoplethysmography — Baseline, week 3, week 6
  Photoplethysmography associated with the clinical response to tVNS
• Change from baseline in electrogastrogram — Baseline, week 3, week 6
  Electrogastrogram associated with the clinical response to tVNS
• Change from baseline in the functional status of brainstem nuclei — Baseline, week 6
  Functional status of selected brainstem nuclei (by fMRI) associated with the clinical response to tVNS
• Change from baseline in the response patterns in the reward anticipation task — Baseline, week 6
  Response patterns in the reward anticipation task (by fMRI) with the clinical response to tVNS
• Change from baseline in motor activity — Continuously starting from baseline up to week 6
  Motor activity changes, measured by actigraph, associated with the clinical response to tVNS
• Change from baseline in heart rate — Continuously starting from baseline up to week 6
  Heart rate, measured by actigraph, associated with the clinical response to tVNS
• Change from baseline in heart rate variability — Continuously starting from baseline up to week 6
  Heart rate variability, measured by actigraph, associated with the clinical response to tVNS
• Change from baseline in oxygen saturation — Continuously starting from baseline up to week 6
  Oxygen saturation, measured by actigraph, associated with the clinical response to tVNS
• Change from baseline in skin temperature — Continuously starting from baseline up to week 6
  Skin temperature, measured by actigraph, associated with the clinical response to tVNS
• Investigation of gene expression changes — Baseline, week 3, week 6
  Gene expression changes over time (based on material extracted from peripheral blood)
• Investigation of epigenetic changes — Baseline, week 3, week 6
  Epigenetic changes over time (based on material extracted from peripheral blood)
• Investigation of protein changes — Baseline, week 3, week 6
  Protein changes over time (based on material extracted from peripheral blood)
• Investigation of lipid changes — Baseline, week 3, week 6
  Lipid changes over time (based on material extracted from peripheral blood)
• Investigation of electrolyte changes — Baseline, week 3, week 6
  Electrolyte changes over time (based on material extracted from peripheral blood)
• Investigation of immunophenotypic changes — Baseline, week 3, week 6
  Immunophenotypic changes over time (based on material extracted from peripheral blood)
• Microbiome changes — Baseline, week 3, week 6
  Microbiome changes (bacteria strains and metabolites) over time
• Genetics — Baseline
  Genotyping based on material extracted from peripheral blood

Trial sites (1)

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