Transcutaneous Vagus Nerve Stimulation (tVNS) for Improved Recovery After Exertion.

NCT06510985 | Not Yet Recruiting

• 1 other identifier: TUE012_tvns_longCovid
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post-COVID-19 Syndrome

Keywords

Post-COVID-19 Syndrome; taVNS; effort; fatigue; heart rate

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Stimulation-induced changes in heart rate variability

  during 6-week tVNS compared to during 6-week low-intensity stimulation phase

• Stimulation-induced changes in physical activity

  during 6-week tVNS compared to during 6-week low-intensity stimulation phase

• Stimulation-induced changes in wanting the monetary rewards

  Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase

• Stimulation-induced changes in exertion

  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

  during 6-week tVNS compared to during 6-week low-intensity stimulation phase

Other Outcomes (2)

• Sensor-based data will be included in exploratory analyses.

  during 6-week tVNS compared to during 6-week low-intensity stimulation phase

• Changes in Questionnaires

  Pre treatment vs. after 6-week tVNS vs. after 6-week low-intensity stimulation phase

Study Arms (2)

Monitoring with high/low-intensity stimulation

EXPERIMENTAL

The cross-over design includes one group which starts with high-intensity stimulation (n = 40) and another group, who starts with low-intensity stimulation (n = 40). The first group receives at first high-intensity for 6 weeks, followed by a low-intensity stimulation phase for 6 weeks. To control for placebo effects, other forty individuals start with the 6-week low-intensity stimulation phase followed by 6 weeks of high-intensity tVNS stimulation phase.

Device: transcutaneous vagus nerve stimulation; Behavioral: Monitoring; Device: cardiowatch bracelet

Monitoring without stimulation

EXPERIMENTAL

Another group of patients is included as a control group (n = 40) undergoing 'treatment as usual' for Long/Post Covid. This group of participants receive the same monitoring throughout their participation during 12 weeks as the Stimulation-Group. As there is no standardized treatment protocol for Long/Post Covid, 'treatment as usual' implies a supportive approach. This group of participants have the option to receive taVNS stimulation after participating in the study.

Behavioral: Monitoring; Device: cardiowatch bracelet

Interventions

transcutaneous vagus nerve stimulation DEVICE

The study employs a CE-certified tVNS® E device, ensuring European safety standards (EU regulation 2017/745 on medical devices). This device features a stimulation cycle of 28 seconds on and 32 seconds off, with a 25 Hz impulse frequency. For the high-intensity group, the stimulation intensity will be individually adjusted in the session before starting the high-intensity tVNS stimulation at home. Recommended daily usage is max. 4 hours, after which it automatically shuts off.

Monitoring with high/low-intensity stimulation

Monitoring BEHAVIORAL

Participants are monitored over 12 weeks using a combination of questionnaires and ecological momentary assessment. This approach allows for a comprehensive assessment of the patient's health and well-being.

Monitoring with high/low-intensity stimulation; Monitoring without stimulation

cardiowatch bracelet DEVICE

The study employs the medically certified cardiowatch bracelet from Corsano (CE-MDR medical certification, FDA 510 (k) cleared) for continuous monitoring of vital signals, such as heart rate, heart rate variability, breathing rate, SpO2, physical activity and sleep.

Monitoring with high/low-intensity stimulation; Monitoring without stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• individuals who have previously tested positive for SARS-CoV-2 infection (preferred PCR-Test) or have a medically confirmed history of COVID-19 (preferred SARS-CoV-2 Antibody-test) and have persistent symptoms (including Post-COVID) .
• clinical diagnoses made by physician: individuals are included with at least one persistent symptom for at least 4 weeks (Long-COVID) or at least 8 weeks (Post-COVID) following the SARS-CoV-2 infections, such as fatigue, shortness of breath, brain fog, headaches, irritability, cognitive difficulties, muscle or joint pain, sleep disturbances, etc.
• Participants should not have an alternative explanation for their persistent symptoms, ruling out other medical or psychiatric conditions.

You may not qualify if:

• lack of capacity for consent
• insufficient German language skills: Participants must have sufficient (B2 German) language skills to understand the informed consent form, study procedures, and questionnaires.
• Intensive Care Unit treatment during COVID-19 infection
• BMI \> 18.5 \& BMI \< 35 kg/m2
• Lifetime (according to DSM 5):
• brain injury, stroke, epilepsy, or history of seizures
• schizophrenia
• bipolar disorder
• severe substance use disorders, except tobacco
• cardiac arrhythmia, coronary heart disease
• month prevalence: pregnancy or nursing
• active implant (pacemaker, cochlear implant, implanted electrode device) and cerebral shunts
• required permanent use of left-sided hearing aid
• ear infections, open wounds, or impaired skin at electrode sites

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

Department of Psychiatry & Psychotherapy, University of Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Nils B. Kroemer, Prof. Dr.

  Department of Psychiatry & Psychotherapy, University of Tübingen,Tübingen, 72076

  PRINCIPAL INVESTIGATOR

• Andreas J. Fallgatter, Prof. Dr.

  Department of Psychiatry & Psychotherapy, University of Tübingen,Tübingen, 72076

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nils B. Kroemer, Prof. Dr.

CONTACT

+4922828711151; nils.kroemer@uni-tuebingen.de

Andreas Stengel, Prof. Dr.

CONTACT

+497071 29-86714; andreas.stengel@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 19, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 19, 2024

Record last verified: 2024-04

Locations

DE (1)