Transcutaneous Auricular Vagus Nerve Stimulation for Persistent Post-concussion Symptoms

NCT07017257 | Recruiting

• 1 other identifier: 2024-373
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Persistent Post-concussive Symptoms

Keywords

Vagus nerve stimulation; Transcutaneous electrical nerve stimulation; Non-invasive brain stimulation; Persistent post-concussive symptoms; High-density EEG

Outcome Measures

Primary Outcomes (2)

• Effects of taVNS on symptom severity in patients with PPCS

  The investigators will evaluate the effects of taVNS on the severity of PPCS, as measured by the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ consists of 16 items scored on a 5-point Likert scale (0 = not experienced at all, 4 = severe problem). Total scores range from 0 to 64, with higher scores indicating worse symptom severity. The RPQ will be administered at four time points: baseline, mid-treatment, post-intervention, and one-month follow-up.

  From enrollment to the end of the study at 6 weeks (including follow-up).

• Effects of taVNS on brain activity in patients with PPCS

  The investigators will assess the effects of taVNS on brain activity using electroencephalography (EEG). Specific metrics analyzed will include: * Power spectral density across frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). * Functional connectivity patterns across cortical regions based on EEG coherence or phase-locking value. These parameters will be extracted from EEG data collected before and after the first and final taVNS sessions.

  From enrollment to the end of the treatment at 2 weeks.

Secondary Outcomes (10)

• Effects of taVNS on cognitive functions in patients with PPCS

  From enrollment to the end of the treatment at 2 weeks.

• Effects of taVNS on verbal memory in patients with PPCS

  From enrollement to the end of the treatment at 2 weeks.

• Effects of taVNS on heart rate variability in patients with PPCS

  From enrollment to the end of the treatment at 2 weeks.

• Effects of taVNS on headaches in patients with PPCS

  From enrollment to the end of the study at 6 weeks (including follow-up).

• Effect of taVNS on sleep quality in patients with PPCS

  From enrollment to the end of the study at 6 weeks (including follow-up).

Study Arms (2)

Active taVNS

EXPERIMENTAL

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.

Device: Active taVNS

Sham taVNS

SHAM COMPARATOR

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.

Device: Sham taVNS

Interventions

Active taVNS DEVICE

Patients will receive active taVNS for 15 consecutive days, with each session lasting 30 minutes. The stimulation will target the cymba conchae of the left ear and will consist of alternating 30-second on and 30-second off periods. The current intensity will range from 1 to 3 mA, adjusted to the patient's pain threshold, with a pulse width of 250 μsec and a frequency of 25Hz.

Active taVNS

Sham taVNS DEVICE

Patients will receive sham taVNS for 15 consecutive days, with each session lasting 30 minutes. The stimulation will target the cymba conchae of the left ear and will consist of alternating 30-second on and 30-second off periods. The current intensity will be fixed at 100 µA, with a pulse width of 250 μsec and a frequency of 25 Hz.

Sham taVNS

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Liege: lead
• University Hospital Sart Tilman, Liege: collaborator

Study Sites (1)

University Hospital of Liège

Liège, Liège, 4000, Belgium

RECRUITING

Study Officials

• Nicolas Lejeune, MD, PhD

  NeuroRehab & Consciousness Clinic, Neurology Department , University Hospital of Liège

  PRINCIPAL INVESTIGATOR

• Aurore Thibaut, PT, PhD

  NeuroRecovery Lab, GIGA-Consciousness, GIGA Institute, University of Liège

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mélanie Louras, MSc

CONTACT

+32479925739; melanie.louras@uliege.be

Aurore Thibaut, PT, PhD

CONTACT

+3243233612; athibaut@uliege.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: June 12, 2025
• Study Start: May 28, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 12, 2025

Record last verified: 2025-05

Locations

BE (1)