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NCT Number: NCT03887715

A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression

Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.

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Key information

Conditions

Treatment Resistant Depression Behavior Behavioral Symptoms Depression Depressive Disorder Depressive Disorder, Treatment-Resistant Mental Disorders Mood Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

About this study

A prospective, multi-center, randomized, controlled, blinded trial of subjects implanted with VNS Therapy. Active treatment and no stimulation control are randomized, at least two weeks after implantation and observed for 12-months.

After completing the 12 month endpoint in the RCT portion of the study, all RECOVER subjects will transition into the prospective, open-label, longitudinal portion of the study. Subjects in the control arm of RECOVER will be activated after completing the 12 month endpoint.

After completion of enrollment in the RCT portion or meeting of interim success criterion (whichever comes first), up to 5,800 new subjects may enroll directly into the open-label,prospective, longitudinal study. These subjects will participate in the study for approximately 5 years.

The study has been designed in accordance with The Centers for Medicare and Medicaid Services coverage with evidence development (CED) decision entitled "Decision Memo for Vagus Nerve Stimulation (VNS) for Treatment Resistant Depression (TRD) (CAG-00313R2).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have had at least four episodes of MDD, including the current episode.

The patient's depressive illness meets a minimum criterion of four prior failed treatments of adequate dose and duration as measured by a tool designed for this purpose.

The patient is experiencing a major depressive episode (MDE) as measured by a guideline recommended depression scale assessment tool on two visits, within a 45-day span prior to implantation of the VNS device.

Patients must maintain a stable medication regimen for at least four weeks before device implantation.

Exclusion criteria

Current or lifetime history of psychotic features in any MDE;

Current or lifetime history of schizophrenia or schizoaffective disorder;

Current or lifetime history of any other psychotic disorder;

Current or lifetime history of rapid cycling bipolar disorder;

Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;

Current suicidal intent; or

Treatment with another investigational device or investigational drugs.

Treatment and study plan

Vagus Nerve Stimulation (VNS)

Device

VNS is an implantable device that delivers stimulation to the vagal nerve.

Other names: VNS

Primary outcomes

  1. Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response

    Time frame: 12 months post randomization

    The rate of response defined as person months of response/total months of study participation where response is at least a 50% reduction from baseline in MADRS total score. Subjects discontinuing the study before the endpoint assessment will be considered as non-responders for each successive month after discontinuance.

  2. Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response

    Time frame: Baseline up to 12 Months

    Time from randomization to the first observed MADRS response.

  3. Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission

    Time frame: Baseline up to 12 Months

    Time from randomization to the first observed MADRS remission.

  4. Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response

    Time frame: Baseline up to 12 Months

    Duration of MADRS response, defined as the number of consecutive months from first observed MADRS response to the first assessment of MADRS response relapse.

  5. Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission

    Time frame: Baseline up to 12 Months

    The rate of remission is defined as total number of months in remission divided by total months of expected study participation. Subjects discontinuing the study before the endpoint assessment will be considered as non-in-remission for each successive month after discontinuance

  6. Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response

    Time frame: Baseline up to 12 Months

    Maximum duration of MADRS response, defined as the maximum number of consecutive months in response (only for subjects experiencing MADRS response).

  7. Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission

    Time frame: Baseline up to 12 Months

    Duration of MADRS remission, defined as the number of consecutive months from first observed MADRS remission to the first assessment of MADRS remission relapse (defined score > 20).

  8. Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission

    Time frame: Baseline up to 12 Months

    Maximum duration of MADRS remission, defined as the maximum number of consecutive months in remission (only for subjects experiencing MADRS remission).

  9. Assess all Adverse Events

    Time frame: Implant to 12 Months

    All adverse events, with a focus on device or procedure-related serious adverse events.

  10. WHO Disability Assessment Schedule (WHODAS) Changes in scores over time

    Time frame: Baseline to 12 Months

  11. Health Outcome Scale (EQ-5D-L) Changes in scores over time

    Time frame: Baseline to 12 Months

  12. Clinical Global Impressions Scale - Improvement (CGI-I) Response

    Time frame: 12 months post randomization

    A CGI-I score ≤ 2 at 12 months from randomization. Subjects discontinuing the study before the 12 months assessment will be considered as not in response for each successive month after discontinuance.

  13. Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality

    Time frame: Implant to 12 Months

    Suicide attempts as measured by items #10 & #12 in S-STS scale

Study contacts

Contact information is provided by the study sponsor or research team.

Laura Yates, BSN

CONTACT

[email protected]

281-228-7200

Sponsors and collaborators

Lead sponsor

LivaNova

Industry

Registry information

Acronym: RECOVER

Important dates

Study start
2019
Primary completion
2028
Study completion
2030
First posted
Mar 25, 2019
Registry last updated
Jun 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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