Transcutaneous Vagus Nerve Stimulation (tVNS) for Improved Recovery After Exertion.
NCT Number: NCT06510985
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Post-COVID-19 Syndrome
Interventions: DEVICE: transcutaneous vagus nerve stimulation|BEHAVIORAL: Monitoring|DEVICE: cardiowatch bracelet
Sponsor: University Hospital Tuebingen
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 120
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2024-07-19
Completion Date: 2027-12
Locations: Department of Psychiatry & Psychotherapy, University of Tübingen, Tübingen, BW, 72076, Germany

Summary:
Widespread infection with SARS-CoV-2 has resulted in millions of people having Post-COVID. Post-COVID is a complex, non-monolithic disease with diverse clinical manifestations. Symptoms range from fatigue, brain fog, muscle aches and shortness of breath, affecting multiple organ systems simultaneously. To directly address this multi-organ component of Post-COVID, innovative treatment methods are urgently needed. One potential treatment that we will investigate in our study, is the intervention via the vagus nerve, as the cranial nerve plays a central role in communication between the body and the brain and influences targeted behavior. This innovative approach is based on our clinically relevant findings regarding the effects where acute tVNS increased the level of effort (Neuser et al., 2020; Ferstl et al., 2021), specifically targeting a key symptom of Post-COVID. In the proposed study, the investigators aim to investigate the effectiveness of transcutaneous vagus nerve stimulation (tVNS) as a non-invasive, self-administered treatment for Post-COVID symptoms at home. To evaluate the clinically relevant effects of repeated taVNS application (high-intensity stimulation), the investigators will employ a randomized cross-over design to investigate stimulation-induced changes in fatigue, depression and motivation to work for reward compared to low-intensity stimulation and to a control group.

Primary Outcome Measures: Stimulation-induced changes in invigoration: frequency of button presses during the first seconds of the trial to gain monetary rewards in the Effort Allocation Task., Changes in invigoration to work for rewards are operationalized as the relative increase in the frequency of button presses on an Xbox controller during the first seconds of the trial in the Effort Allocation Task., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in symptoms of depression, Changes in symptoms of depression are measured via the Montgomery Asberg Depression Scale. The MADRS comprises 10 items rated on a scale from 0 to 6 to compute a sum score with higher scores indicating severe symptoms of depression., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in physical and mental aspects of fatigue, Changes in fatigue are measured by the Chalder Fatigue scale. The CFS comprises 11 questions rated on a 4-point Likert scale to compute a sum score.

It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase
Secondary Outcome Measures: Stimulation-induced changes in heart rate variability, Changes in heart rate variability are measured by a cardiowatch bracelet to evaluate autonomic nervous system activity.

It will be measured over three months daily., during 6-week tVNS compared to during 6-week low-intensity stimulation phase|Stimulation-induced changes in physical activity, Changes in physical activity are measured by step count per day, which are recorded by the cardiowatch bracelet.

It will be measured over three months daily., during 6-week tVNS compared to during 6-week low-intensity stimulation phase|Stimulation-induced changes in wanting the monetary rewards, Changes in wanting monetary rewards are measured via a visual analogue scale rating after each effortful trial in the Effort Allocation Task.

It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in exertion, Changes in exertion are measured via a visual analogue scale rating after each effortful trial.

It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in the motivation to invest effort: the discounting rate reflecting rewards devalued by effort, Changes in the motivation to invest effort is quantified by estimating the participant-specific discounting factor (k) and the inverse temperature parameter (β), which are derived by fitting the participant's observed choice behavior in the effort discounting task to discounting models.

It will be measured at least twice a week over three months., during 6-week tVNS compared to during 6-week low-intensity stimulation phase|Stimulation-induced changes in resting energy expenditure, Changes in resting energy expenditure are measured by indirect calorimetry. It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in metabolic and inflammatory markers, Metabolic hormone levels and inflammatory markers are assessed from blood samples.

It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in health-related quality of life, Changes in health-related quality of life are measured by the Short-Form-12 health survey (SF-12), consisting of 12 questions (weighted sum score).

It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in mood, Changes in positive and negative mood ratings are measured with the PANAS questionnaire (scale 1-5) It will be measured three times six weeks apart., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in maintenance:the average relative frequency across the complete trial to gain monetary rewards in the Effort Allocation Task., Changes in motivation to work for rewards are operationalized as the average relative increase in the frequency of button presses on an Xbox controller across the complete trial in the Effort allocation task., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase|Stimulation-induced changes in heart rate, Changes in heart rate are measured by a cardiowatch bracelet depending on physical activity phases, during 6-week tVNS compared to during 6-week low-intensity stimulation phase
Other Outcome Measures: Sensor-based data will be included in exploratory analyses., Changes in sensory-based data are measured by a cardiowatch bracelet, during 6-week tVNS compared to during 6-week low-intensity stimulation phase|Changes in Questionnaires, Questionnaires will be included in exploratory analyses and as a confounding variable., Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase