Transcutaneous Auricular Vagus Nerve Stimulation for Persistent Post-concussion Symptoms (taVNS-PPCS)

University of Liege

Status: Enrolling

Conditions: Persistent Post-concussive Symptoms

Treatments: Device: Sham taVNS; Device: Active taVNS

Study type: Interventional

Funder types: Other

Identifiers

NCT07017257

2024-373

Details and patient eligibility

About

Persistent post-concussive symptoms (PPCS) affect a significant proportion of individuals following a concussion, leading to debilitating impacts on their quality of life and work capacity. Currently, effective treatments for PPCS are limited, despite their lasting and debilitating impact. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation technique, holds promise as a therapeutic option by leveraging the bottom-up modulation of brain activity via the auricular branch of the vagus nerve. This study aims to evaluate the neurophysiological and clinical effects of taVNS on brain activity and symptomatology in patients with PPCS through a randomized, controlled, double-blind trial.

Full description

PPCS occur in 30-50% of individuals following a concussion and can persist for months, causing somatic complaints (e.g., headaches and dizziness), cognitive impairments (e.g., memory and concentration issues), emotional disturbances (e.g., anxiety and depression), and sleep disorders. Despite their long-term consequences, effective treatments for PPCS remain scarce. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-invasive technique that stimulates the auricular branch of the vagus nerve to induce bottom-up effects on brain activity, potentially alleviating PPCS.

This randomized, controlled, double-blind clinical trial will evaluate the cumulative and direct neurophysiological and clinical effects of taVNS (tVNS Technologies GmbH, Germany) in 48 patients aged 18 to 65 years who experienced a diagnosed concussion between 4 weeks and 1 year prior to enrollment and suffer from PPCS. Participants will be randomized to either an active taVNS group or a sham stimulation group.

Patients will undergo a total of 15 taVNS sessions over two weeks, including two visits at the University Hospital of Liège (first and last session) and 13 self-administered sessions at home. Symptom severity, including headaches, depression, anxiety, sleep disturbances, and overall quality of life, will be measured using validated questionnaires, while cognitive function (i.e., attention, working memory, executive functions) will be assessed through neuropsychological tests. Additionally, electroencephalographic (EEG) and electrocardiogram (ECG) recordings will be used to measure changes in brain activity and heart rate, respectively, focusing on alterations in power spectral density and functional connectivity patterns that may correlate with clinical improvements.

Follow-up assessments will occur one-month post-intervention via a phone call to collect questionnaires assessing symptom severity and quality of life.

This protocol aims to provide robust evidence on the efficacy and mechanisms of taVNS for PPCS while advancing our understanding of the neurophysiological changes associated with this therapeutic approach.

Interim analyses will be conducted after the inclusion of 24 patients to evaluate preliminary data. These analyses will also allow for adjustments to the sample size, if necessary, to maintain the study's statistical power.

Patients who did not complete 80% of the sessions (12 sessions) will be excluded from the study.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age between 18 and 65;
• Between 4 weeks and 1-year post-diagnosis of a concussion;
• Score equal or above 16 on the Rivermead Post-Concussion Questionnaire;
• Intact skin at the electrode site.

Exclusion criteria

• History of chronic neurological or psychological disorders (still untreated 6 months preceding inclusion);
• Pregnancy or breastfeeding;
• Presence of an active implant (e.g., pacemaker, cochlear implant);
• History of myocardial infarction or cardiac arrhythmia;
• Excessive alcohol consumption (> 14 drinks per week) and/or drug (> 1x/week) use within the past 6 months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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48 participants in 2 patient groups

Active taVNS

Experimental group

Description:

Patients will undergo 15 sessions of 30-min active taVNS applied to the cymba conchae of the left ear. Clinical assessments-including symptom severity questionnaires and neuropsychological tests-along with neurophysiological recordings (hd-EEG and electrocardiography) will be conducted on the first (S1) and final (S15) days of the intervention. The remaining 13 sessions (S2-14) will be self-administered by patients at home. To monitor safety, participants will report any side effects after each session. To monitor adherence, the device will record the time and duration of each stimulation session. Blinding efficacy will be evaluated at the end of the intervention by asking participants to indicate whether they believe they received active or sham stimulation, and to rate their confidence in that response. A follow-up assessment will occur one month after the intervention, during which symptom severity questionnaires will be administered via a phone interview.

Treatment:

Device: Active taVNS

Sham taVNS

Sham Comparator group

Description:

Patients will undergo 15 sessions of 30-min sham taVNS applied to the cymba conchae of the left ear. Clinical assessments-including symptom severity questionnaires and neuropsychological tests-along with neurophysiological recordings (hd-EEG and electrocardiography) will be conducted on the first (S1) and final (S15) days of the intervention. The remaining 13 sessions (S2-14) will be self-administered by patients at home. To monitor safety, participants will report any side effects after each session. To monitor adherence, the device will record the time and duration of each stimulation session. Blinding efficacy will be evaluated at the end of the intervention by asking participants to indicate whether they believe they received active or sham stimulation, and to rate their confidence in that response. A follow-up assessment will occur one month after the intervention, during which symptom severity questionnaires will be administered via a phone interview.

Treatment:

Device: Sham taVNS