Clinical trial NCT07017257: Transcutaneous Auricular Vagus Nerve Stimulation for Persistent Post-concussion Symptoms
Official title: Effects of Transcutaneous Auricular Vagus Nerve Stimulation in Patients With Persistent Post-concussion Symptoms: a Randomized Double-blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Persistent Post-concussive Symptoms
Keywords: Vagus nerve stimulation
Transcutaneous electrical nerve stimulation
Non-invasive brain stimulation
Persistent post-concussive symptoms
High-density EEG
Lead sponsor: University of Liege
Sponsor class: OTHER
Collaborators: name: University Hospital Sart Tilman, Liege
First posted: 2025-06-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effects of taVNS on symptom severity in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on brain activity in patients with PPCS
timeFrame: From enrollment to the end of the treatment at 2 weeks.
Secondary outcomes:
measure: Effects of taVNS on cognitive functions in patients with PPCS
timeFrame: From enrollment to the end of the treatment at 2 weeks.
measure: Effects of taVNS on verbal memory in patients with PPCS
timeFrame: From enrollement to the end of the treatment at 2 weeks.
measure: Effects of taVNS on heart rate variability in patients with PPCS
timeFrame: From enrollment to the end of the treatment at 2 weeks.
measure: Effects of taVNS on headaches in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effect of taVNS on sleep quality in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on daytime sleepiness in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on sleep changes in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on depressive symptoms in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on anxiety symptoms in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
measure: Effects of taVNS on quality of life in patients with PPCS
timeFrame: From enrollment to the end of the study at 6 weeks (including follow-up).
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: University Hospital of Liège
Study officials:
affiliation: NeuroRehab & Consciousness Clinic, Neurology Department , University Hospital of Liège
name: Nicolas Lejeune, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NeuroRecovery Lab, GIGA-Consciousness, GIGA Institute, University of Liège
name: Aurore Thibaut, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References: