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REVEAL Study: Vagus Nerve Stimulation for Epilepsy and Depression

This study, called REVEAL, is looking at how vagus nerve stimulation (VNS) affects the body's systems, including the autonomic nervous system (which controls automatic body functions), cardiovascular system, immune system, and metabolism. It's for people aged 18 and older who already have a VNS device implanted because they have either drug-resistant epilepsy or major depressive disorder. Researchers will compare the effects of different VNS settings by taking physiological recordings and blood samples. The main goal is to understand how VNS works, not to test a new treatment. The study is currently unclear about its recruitment status and plans to enroll 144 participants. Success will be measured by changes in muscle sympathetic nerve activity (burst incidence, frequency, and area) with VNS over 12 weeks.

Study design
This interventional study plans to enroll 144 participants. It is not specified if it is randomized or blinded.
What's involved
Participants will have physiological recordings and blood draws at various times throughout the study.
Compensation
Not stated in the trial record.
Follow-up
Changes in muscle sympathetic nerve activity will be measured at baseline and 12 weeks.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06143293

RESEARCH EVALUATING VAGAL EXCITATION AND ANATOMICAL LINKS

Active, Not Recruiting
NAAges 18+InterventionalBasic science
University of Minnesota
~144 participants
Updated 2026-06-24 on ClinicalTrials.gov
What's tested:Vagus nerve stimulation device: acute and chronic administration of investigational vagus nerve stimulation parameters

At a glance

Recruiting sites
0 of 7 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change in Muscle Sympathetic Nerve Burst Incidence with Vagus nerve stimulation
Measured over baseline and 12 weeks
+35 more outcomes measured

Conditions

Epilepsy
Depressive Disorder

Explore related trials

Depressive disorderSeizure Disorder

Where it's being run

7 sites across 6 states
Victoria2
California1
Minnesota1
Missouri1
Nebraska1
South Carolina1

Study leadership

  • John Osborn, PhD · PRINCIPAL_INVESTIGATOR · University of Minnesota

Who to contact

This trial hasn't published a contact. View it on ClinicalTrials.gov

Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Participant must be at least 18 years old.
Participant must have the capacity to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Participant must be enrolled in an active health insurance plan that will cover the costs associated with standard health care services and injuries.
Participant must have been previously implanted with a VNS device for the clinical indication of Major Depressive Disorder (MDD).
Participant must be able and willing to complete the evaluations and procedures described in the study protocol.
Participant's usage of concomitant medications must be stable for two months preceding study enrollment and the participant must be able and willing to maintain stable usage of any concomitant medications from the day of enrollment through the completion of Study Visit 2.
Participant that is of childbearing potential must be adequately protected from conception or willing to use an acceptable method of birth control over the entire study duration (acceptable birth control includes abstinence, barrier methods, hormonal methods, sterilization and fertility awareness).
Participant must be at least 18 years old.
Participant must have the capacity to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Participant must be enrolled in an active health insurance plan that will cover the costs associated with standard health care services and injuries.
Participant has a diagnosis of chronic (≥ 2 years) or ≥ 4 recurrent depressive episodes as defined by DSM-5 criteria documented using the MINI criteria and psychiatric medical record review. Participant must have VNS therapy clinically indicated.
Participant has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories in the current depressive episode according to the Antidepressant Treatment History Form (ATHF).
Participant must have a score on the baseline administration of the Montgomery-Åsberg Depression Rating Scale (MADRS) of ≥ 22.
Participant must be able and willing to complete the evaluations and procedures described in the study protocol.
Participant's usage of concomitant medications must be stable for two months preceding study enrollment and the participant must be able and willing to maintain stable usage of any concomitant medications from the day of enrollment through the completion of Study Visit 2.
Participant that is of childbearing potential must be adequately protected from conception or willing to use an acceptable method of birth control over the entire study duration (acceptable birth control includes abstinence, barrier methods, hormonal methods, sterilization and fertility awareness).
Participant must be at least 18 years old.
Participant must have the capacity to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Participant must be enrolled in an active health insurance plan that will cover the costs associated with standard health care services and injuries.
Participant must have been previously implanted with a VNS device for the clinical indication of drug resistant epilepsy.
Participant has not had demonstrable benefit from the implanted VNS device in terms of epilepsy (seizure frequency or seizure severity) or related epilepsy comorbidities (mood, cognition, quality of life), with no definite improvement or suboptimal improvement in seizure control.
Apart from epilepsy, the participant should be medically and neurologically stable.
Participant must be able and willing to complete the evaluations and procedures described in the study protocol.
Participant's usage of concomitant medications must be stable for two months preceding study enrollment and the participant must be able and willing to maintain stable usage of any concomitant medications from the day of enrollment through the completion of Study Visit 2.
Participant that is of childbearing potential must be adequately protected from conception or willing to use an acceptable method of birth control over the entire study duration (acceptable birth control includes abstinence, barrier methods, hormonal methods, sterilization and fertility awareness).
Participant must be at least 18 years old.
Participant must have the capacity to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Participant must be enrolled in an active health insurance plan that will cover the costs associated with standard health care services and injuries as well as the costs associated with the VNS implantation surgery.
Participant is diagnosed with drug resistant epilepsy, with continuing seizures despite adequate trials of at least 2 appropriate antiseizure drugs (ASDS) with therapeutic serum concentrations as per the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies.
Apart from epilepsy, the participant should be medically and neurologically stable.
Participant must be able and willing to complete the evaluations and procedures described in the study protocol.
Participant's usage of concomitant medications must be stable for two months preceding study enrollment and the participant must be able and willing to maintain stable usage of any concomitant medications from the day of enrollment through the completion of Study Visit 2.
Participant that is of childbearing potential must be adequately protected from conception or willing to use an acceptable method of birth control over the entire study duration (acceptable birth control includes abstinence, barrier methods, hormonal methods, sterilization and fertility awareness).
Participant has been informed of his or her eligibility for resective surgery as a potential alternative to receiving, as standard of care, the VNS device that is required for participation in this study, if such surgery is a reasonable option.

Exclusion

Participant has a prior implantable stimulation device, other than a VNS device for the clinical indication of Major Depressive Disorder (MDD).
Participant currently uses or is expected during the study to use short-wave diathermy, microwave, diathermy, or therapeutic ultrasound diathermy.
Participant is judged by the investigator to be acutely suicidal (e.g. has made specific plans or preparations to commit suicide or as indicated by the Sheehan Suicidality Tracking Scale) within the last 30 days prior to study enrollment.
Participant has made a suicide attempt within the previous 6 months from study enrollment.
Participant has a history of one or more schizophrenia-spectrum or other psychotic disorders including schizophrenia, schizoaffective disorder, delusional disorder, or a current or lifetime major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the MINI criteria.
Participant has a history of significant borderline or severe personality disorder as determined by clinical judgment.
Participant has an active primary diagnosis of obsessive-compulsive, eating, or post-traumatic stress disorder based on the MINI criteria.
Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 without sustained remission of 12 months or longer.
Participant has a presence of any type of dementia, major neurocognitive disorder, or cognitive or psychiatric deficit as determined by clinical judgment.
Participant has a history of rapid cycling bipolar disorder I or II.
Participant currently receives treatment with another investigational device or investigational drug other than the REVEAL study, or has participated in another drug or device trial within the preceding 30 days before enrollment.
Participant is not able or willing to use their dominant arm, or either upper arm circumference is greater than 50 cm.
Participant does not speak English.
Any other clinical reasons deemed by the investigators of the study in which the participant would not be an appropriate candidate for the study, such as peripheral vascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.
Participant has a prior implantable stimulation device.
Participant currently uses or is expected during the study to use short-wave diathermy, microwave, diathermy, or therapeutic ultrasound diathermy.
Participant is judged by the investigator to be acutely suicidal (e.g. has made specific plans or preparations to commit suicide or as indicated by the Sheehan Suicidality Tracking Scale) within the last 30 days prior to study enrollment.
Participant has made a suicide attempt within the previous 6 months from study enrollment.
Participant has a history of one or more schizophrenia-spectrum or other psychotic disorders including schizophrenia, schizoaffective disorder, delusional disorder, or a current or lifetime major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the MINI criteria.
Participant has a history of significant borderline or severe personality disorder as determined by clinical judgment.
Participant has an active primary diagnosis of obsessive-compulsive, eating, or post-traumatic stress disorder based on the MINI criteria.
Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 without sustained remission of 12 months or longer.
Participant has a presence of any type of dementia, major neurocognitive disorder, or cognitive or psychiatric deficit as determined by clinical judgment.
Participant has a history of rapid cycling bipolar disorder I or II.
Participant currently receives treatment with another investigational device or investigational drug other than the REVEAL study, or has participated in another drug or device trial within the preceding 30 days before enrollment.
Participant with vocal cord paralysis.
Participant is not able or willing to use their dominant arm, or either upper arm circumference is greater than 50 cm.
Participant does not speak English.
Any other clinical reasons deemed by the investigators of the study in which the participant would not be an appropriate candidate for the study, such as peripheral vascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.
Participant has demonstrable benefit from implanted VNS device in terms of epilepsy (seizure frequency or seizure severity) or epilepsy comorbidity (mood, cognition, or quality of life), with seizure freedom or clinical benefit.
Participant has a prior implantable stimulation device, other than a VNS device for the clinical indication of refractory focal Epilepsy.
Participant currently uses or is expected during the study to use short-wave diathermy, microwave, diathermy, or therapeutic ultrasound diathermy.
Participant has been hospitalized for a psychiatric condition within the preceding 6 months or has had a history of psychosis within the preceding two years (excluding postictal psychosis).
Participant has experienced unprovoked status epilepticus in the preceding year.
Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 without sustained remission of 12 months or longer.
Participant currently receives treatment with another investigational device or investigational drug other than the REVEAL study, or has participated in another drug or device trial within the preceding 30 days before enrollment.
Participant is not able or willing to use their dominant arm, or either upper arm circumference is greater than 50 cm.
Participant does not speak English.
Any other clinical reasons deemed by the investigators of the study in which the participant would not be an appropriate candidate for the study, such as peripheral vascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.
Participant has a prior implantable stimulation device.
Participant currently uses or is expected during the study to use short-wave diathermy, microwave, diathermy, or therapeutic ultrasound diathermy.
Participant has been hospitalized for a psychiatric condition within the preceding 6 months or has had a history of psychosis within the preceding two years (excluding postictal psychosis).
Participant has experienced unprovoked status epilepticus in the preceding year.
Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 without sustained remission of 12 months or longer.
Participant currently receives treatment with another investigational device or investigational drug other than the REVEAL study, or has participated in another drug or device trial within the preceding 30 days before enrollment.
Participant with vocal cord paralysis.
Participant is not able or willing to use their dominant arm, or either upper arm circumference is greater than 50 cm.
Participant does not speak English.
Any other clinical reasons deemed by the investigators of the study in which the participant would not be an appropriate candidate for the study, such as peripheral vascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.

What this trial measures

  • Change in Muscle Sympathetic Nerve Burst Incidence with Vagus nerve stimulationbaseline and 12 weeks

    Changes in muscle sympathetic nerve activity burst incidence (bursts/100 heart beats) measured using microneurography of the fibular nerve in response to various vagus nerve stimulation parameters delivered acutely before and after 12 weeks of chronic vagus nerve stimulation.

  • Change in Muscle Sympathetic Nerve Burst Frequency with Vagus nerve stimulationbaseline and 12 weeks

    Changes in muscle sympathetic nerve activity burst frequency (bursts/min) measured using microneurography of the fibular nerve in response to various vagus nerve stimulation parameters delivered acutely before and after 12 weeks of chronic vagus nerve stimulation.

  • Change in Muscle Sympathetic Nerve Burst Area with Vagus nerve stimulationbaseline and 12 weeks

    Changes in muscle sympathetic nerve activity burst area (arbitrary units/min) measured using microneurography of the fibular nerve in response to various vagus nerve stimulation parameters delivered acutely before and after 12 weeks of chronic vagus nerve stimulation

  • Effect of Vagus nerve stimulation on Isometric Hand Grip-mediated changes in Heart Ratebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in heart rate (bpm) elicited by the isometric hand grip exercise, measured using electrocardiography

  • Effect of Vagus nerve stimulation on Isometric Hand Grip-mediated changes in Blood pressurebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in systolic, diastolic, and mean arterial blood pressure (mmHg) elicited by the isometric hand grip exercise, measured using finger cuff.

  • Effect of Vagus nerve stimulation on Isometric Hand Grip-mediated changes in Muscle Sympathetic Nerve Activity (MSNA)baseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in muscle sympathetic nerve activity elicited by the isometric hand grip exercise, measured using microneurography of the fibular nerve

  • Effect of Vagus nerve stimulation on Post-exercise circulatory occlusion-mediated change in Heart Ratebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in heart rate (bpm) elicited by post-exercise circulatory occlusion following the isometric hand grip exercise, measured using electrocardiography.

  • Effect of Vagus nerve stimulation on Post-exercise circulatory occlusion-mediated change in Blood pressurebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in systolic, diastolic, and mean arterial blood pressure (mmHg) elicited by the post-exercise circulatory occlusion following the isometric hand grip exercise, measured using finger cuff

  • Effect of Vagus nerve stimulation on Post-exercise circulatory occlusion-mediated change in Muscle Sympathetic Nerve Activity (MSNA)baseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in muscle sympathetic nerve activity elicited by the post-exercise circulatory occlusion following the isometric hand grip exercise, measured using microneurography of the fibular nerve.

  • Effect of Vagus nerve stimulation on Head up tilt test-mediated change in Heart Ratebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in heart rate (bpm) elicited by a passive head-up tilt test, measured using electrocardiography

  • Effect of Vagus nerve stimulation on Head up tilt test-mediated change in Blood pressurebaseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in systolic, diastolic, and mean arterial blood pressure (mmHg) elicited by a passive head-up tilt test, measured using finger cuff.

  • Effect of Vagus nerve stimulation on Head up tilt test-mediated change in Muscle Sympathetic Nerve Activity (MSNA)baseline and 12 weeks

    The effect Vagus nerve stimulation has on changes in muscle sympathetic nerve activity elicited by a passive head-up tilt test, measured using microneurography of the fibular nerve

  • Effect of Vagus nerve stimulation on cardiac dimensionsbaseline and 12 weeks

    The effect of Vagus nerve stimulation on standard measurements of cardiac dimensions (cm, mL) measured using echocardiography

  • Effect of Vagus nerve stimulation on cardiac ejection fractionbaseline and 12 weeks

    The effect of Vagus nerve stimulation on standard measurements of cardiac ejection fraction (%) measured using echocardiography.

  • Effect of Vagus nerve stimulation on cardiac blood flowbaseline and 12 weeks

    The effect of Vagus nerve stimulation on standard measurements of cardiac blood flow (cm/sec) measured using echocardiography and Doppler.

  • Effect of Vagus nerve stimulation on ambulatory systolic blood pressure12 weeks

    The effect of Vagus nerve stimulation on ambulatory systolic blood pressure (mmHg) measured using an ambulatory blood pressure monitor at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on ambulatory diastolic blood pressure12 weeks

    The effect of Vagus nerve stimulation on ambulatory diastolic blood pressure (mmHg) measured using an ambulatory blood pressure monitor at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on ambulatory heart rate12 weeks

    The effect of Vagus nerve stimulation on ambulatory heart rate (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period

  • Effect of Vagus nerve stimulation on ambulatory heart rate while in sinus rhythm12 weeks

    The effect of Vagus nerve stimulation on ambulatory heart rate while in sinus rhythm (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on supraventricular ectopy episodes12 weeks

    The effect of Vagus nerve stimulation on supraventricular ectopy episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on ventricular ectopy episodes12 weeks

    The effect of Vagus nerve stimulation on ventricular ectopy episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on number of supraventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on the number of distinct supraventricular tachycardia episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on duration of supraventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on the duration of supraventricular tachycardia episodes (min) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on heart rate during supraventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on heart rate during supraventricular tachycardia episodes (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on number of ventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on the number of distinct ventricular tachycardia episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on duration of ventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on the duration of ventricular tachycardia episodes (min) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on heart rate during ventricular tachycardia episodes12 weeks

    The effect of Vagus nerve stimulation on heart rate during ventricular tachycardia episodes (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on number of atrial fibrillation episodes12 weeks

    The effect of Vagus nerve stimulation on the number of atrial fibrillation episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period

  • Effect of Vagus nerve stimulation on heart rate during atrial fibrillation episodes12 weeks

    The effect of Vagus nerve stimulation on heart rate during atrial fibrillation episodes (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on duration atrial fibrillation episodes12 weeks

    The effect of Vagus nerve stimulation on duration of atrial fibrillation episodes (minutes) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on number of atrial flutter episodes12 weeks

    The effect of Vagus nerve stimulation on the number of atrial flutter episodes (count) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on heart rate during atrial flutter episodes12 weeks

    The effect of Vagus nerve stimulation on heart rate during atrial flutter episodes (bpm) measured using an ambulatory electrocardiography device at-home over a 24-hour period

  • Effect of Vagus nerve stimulation on duration of atrial flutter episodes12 weeks

    The effect of Vagus nerve stimulation on the duration of atrial flutter episodes (minutes) measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on 2nd degree AV block, Mobitz II12 weeks

    The effect of Vagus nerve stimulation on 2nd degree AV block, Mobitz II occurrence, measured using an ambulatory electrocardiography device at-home over a 24-hour period.

  • Effect of Vagus nerve stimulation on changes in inflammatory/autoimmune biomarkers12 weeks

    Evaluate the change in inflammatory/autoimmune biomarkers before, during, and after 12 weeks of chronic Vagus nerve stimulation using ELISA and CyTOF

  • Effect of Vagus nerve stimulation on changes in metabolites12 weeks

    Evaluate the change in metabolites before, during, and after 12 weeks of chronic Vagus nerve stimulation using Biocrates MxP Quant 500