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

Not Applicable

Recruiting

• Conditions: Treatment Resistant Depression

• Registration Number: NCT03887715
• Lead Sponsor: LivaNova

Brief Summary

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.

Detailed Description

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).

Study Timeline

• Study First Submitted: 2019-03-21
• Study First Submitted QC: 2019-03-21
• Study First Posted: 2019-03-25
• Study Start: 2019-09-26
• Status Verified: 2024-12
• Last Update Submitted: 2025-06-12
• Last Update Posted: 2025-06-13
• Primary Completion: 2028-02-28
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6800

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission	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
Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission	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).
Health Outcome Scale (EQ-5D-L) Changes in scores over time	Baseline to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response	Baseline up to 12 Months	Time from randomization to the first observed MADRS response.
Assess all Adverse Events	Implant to 12 Months	All adverse events, with a focus on device or procedure-related serious adverse events.
Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality	Implant to 12 Months	Suicide attempts as measured by items #10 \& #12 in S-STS scale
Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response	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.
WHO Disability Assessment Schedule (WHODAS) Changes in scores over time	Baseline to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response	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.
Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission	Baseline up to 12 Months	Time from randomization to the first observed MADRS remission.
Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response	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).
Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission	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).
Clinical Global Impressions Scale - Improvement (CGI-I) Response	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.

Trial Locations

Locations (96)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

UAB Huntsville Regional Medical Center; 🇺🇸 Huntsville, Alabama, United States

Access Multi Specialty Medical Clinic, Inc; 🇺🇸 Burlingame, California, United States

CMB Clinical Trials; 🇺🇸 Colton, California, United States

ATP Clinical Research, Inc.; 🇺🇸 Costa Mesa, California, United States

Kaizen Brain Center; 🇺🇸 La Jolla, California, United States

Keck Hospital of USC; 🇺🇸 Los Angeles, California, United States

University of California San Diego; 🇺🇸 San Diego, California, United States

SF-CARE, Inc.; 🇺🇸 San Rafael, California, United States

Syrentis Clinical Research; 🇺🇸 Santa Ana, California, United States

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