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

NCT ID: NCT03887715

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

6800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-26

Study Completion Date

2030-12-31

Brief Summary

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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

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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).

Conditions

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Treatment Resistant Depression

Keywords

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VNS Depression TRD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 randomization of active stimulation vs. no stimulation for 12 months post randomization.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Central Rater and sponsor are blinded in the RCT phase. Sites will need to have an unblinded programmer who is only programming the device and not collecting outcomes data.

Study Groups

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Active

Group will have VNS activated 2 weeks post implant.

Group Type ACTIVE_COMPARATOR

Vagus Nerve Stimulation (VNS)

Intervention Type DEVICE

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

Control

Group will be implanted with VNS but device is not activated for the first 12 months. After 12 months, this group can receive stimulation.

Group Type SHAM_COMPARATOR

Vagus Nerve Stimulation (VNS)

Intervention Type DEVICE

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

Interventions

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Vagus Nerve Stimulation (VNS)

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

Intervention Type DEVICE

Other Intervention Names

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VNS

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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LivaNova

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charles Conway, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

UAB Huntsville Regional Medical Center

Huntsville, Alabama, United States

Site Status RECRUITING

Access Multi Specialty Medical Clinic, Inc

Burlingame, California, United States

Site Status TERMINATED

CMB Clinical Trials

Colton, California, United States

Site Status WITHDRAWN

ATP Clinical Research, Inc.

Costa Mesa, California, United States

Site Status RECRUITING

Kaizen Brain Center

La Jolla, California, United States

Site Status RECRUITING

Keck Hospital of USC

Los Angeles, California, United States

Site Status RECRUITING

University of California San Diego

San Diego, California, United States

Site Status ACTIVE_NOT_RECRUITING

SF-CARE, Inc.

San Rafael, California, United States

Site Status TERMINATED

Syrentis Clinical Research

Santa Ana, California, United States

Site Status WITHDRAWN

Sunrise Research Institute

Boca Raton, Florida, United States

Site Status TERMINATED

Mindful Behavioral Health

Boca Raton, Florida, United States

Site Status RECRUITING

Medycal Research, Inc

Brooksville, Florida, United States

Site Status TERMINATED

Galiz Research LLC

Hialeah, Florida, United States

Site Status RECRUITING

Florida Behavioral Psych

Largo, Florida, United States

Site Status RECRUITING

Segal Trials Corporate

Lauderhill, Florida, United States

Site Status WITHDRAWN

Central Miami Medical Institute, LLC

Miami, Florida, United States

Site Status WITHDRAWN

Clintex Research Group, Inc.

Miami, Florida, United States

Site Status TERMINATED

Research Center Of Florida, Inc

Miami, Florida, United States

Site Status WITHDRAWN

Ocean Blue Medical Research Center

Miami Springs, Florida, United States

Site Status WITHDRAWN

APG Research, LLC

Orlando, Florida, United States

Site Status RECRUITING

Nova Psychiatry Inc.

Orlando, Florida, United States

Site Status RECRUITING

Florida Center for TMS

Orlando, Florida, United States

Site Status TERMINATED

Millenia Psychiatry & Research, Inc

Orlando, Florida, United States

Site Status WITHDRAWN

Quantum Laboratories Inc.

Pompano Beach, Florida, United States

Site Status TERMINATED

Advanced Mental Health Care Inc.

Royal Palm Beach, Florida, United States

Site Status RECRUITING

Florida Center for TMS

Saint Augustine, Florida, United States

Site Status RECRUITING

Stedman Clinical Trials

Tampa, Florida, United States

Site Status RECRUITING

Psychiatric Specialty Center

West Palm Beach, Florida, United States

Site Status TERMINATED

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Medical College of Georgia, Augusta University

Augusta, Georgia, United States

Site Status RECRUITING

PACT Atlanta LLC

Decatur, Georgia, United States

Site Status TERMINATED

IACT Health

Grayson, Georgia, United States

Site Status WITHDRAWN

Psych Atlanta

Marietta, Georgia, United States

Site Status RECRUITING

Pearl Health Clinic

Ammon, Idaho, United States

Site Status WITHDRAWN

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Joliet Center For Clinical Research

Joliet, Illinois, United States

Site Status TERMINATED

AMR- Baber Research, Inc.

Naperville, Illinois, United States

Site Status RECRUITING

Psychiatric Medicine Associates, LLC

Skokie, Illinois, United States

Site Status RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status RECRUITING

Neuroscience Research Institute

Winfield, Illinois, United States

Site Status WITHDRAWN

Advanced Research Institute, Inc.

Indianapolis, Indiana, United States

Site Status TERMINATED

Beacon Medical Group Behavioral Health

South Bend, Indiana, United States

Site Status ACTIVE_NOT_RECRUITING

University Of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

Sheppard Pratt Health System, Inc.

Baltimore, Maryland, United States

Site Status RECRUITING

Clinical Insights

Glen Burnie, Maryland, United States

Site Status WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Precise Research Centers

Flowood, Mississippi, United States

Site Status RECRUITING

Andrew Bishop, MD

Jackson, Mississippi, United States

Site Status TERMINATED

University of Missouri

Columbia, Missouri, United States

Site Status RECRUITING

Psychiatric Care and Research

O'Fallon, Missouri, United States

Site Status RECRUITING

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status RECRUITING

PsychCare Consultants Research

St Louis, Missouri, United States

Site Status RECRUITING

Alivation Research, LLC

Lincoln, Nebraska, United States

Site Status RECRUITING

Healthy Perspective

Nashua, New Hampshire, United States

Site Status RECRUITING

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status WITHDRAWN

University of New Mexico - Psychiatric Center

Albuquerque, New Mexico, United States

Site Status WITHDRAWN

Dent Neurological Institute

Amherst, New York, United States

Site Status RECRUITING

Erie County Medical Center/State University of New York (SUNY) at Buffalo Affiliate

Buffalo, New York, United States

Site Status WITHDRAWN

Trinity Medical

Lewiston, New York, United States

Site Status RECRUITING

Hapworth Research Inc.

New York, New York, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Richmond Behavioral Associates

Staten Island, New York, United States

Site Status WITHDRAWN

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status TERMINATED

State University Of New York Upstate Medical University

Syracuse, New York, United States

Site Status TERMINATED

ManuMind Interventional Psychiatry

Woodbury, New York, United States

Site Status RECRUITING

The Center for Neuropsychiatry and Brain Stimulation (CNBS) ARC Health

Cary, North Carolina, United States

Site Status TERMINATED

Mindpath Care Centers

Raleigh, North Carolina, United States

Site Status TERMINATED

Wake Forest University Health Science

Winston-Salem, North Carolina, United States

Site Status WITHDRAWN

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status WITHDRAWN

The Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

Signature Research Associates, Inc.

Fairlawn, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Charak Center for Health and Wellness

Garfield Heights, Ohio, United States

Site Status RECRUITING

NPC Research

Oklahoma City, Oklahoma, United States

Site Status WITHDRAWN

Rivus Wellness & Research Institute

Oklahoma City, Oklahoma, United States

Site Status TERMINATED

University of Oklahoma School of Community Medicine

Tulsa, Oklahoma, United States

Site Status RECRUITING

Scranton Medical Institutes

Moosic, Pennsylvania, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

Neuroscience and TMS Treatment Center

Brentwood, Tennessee, United States

Site Status RECRUITING

UT Health Austin, Mulva Clinic for the Neurosciences

Austin, Texas, United States

Site Status RECRUITING

BioBehavioral Research of Austin

Austin, Texas, United States

Site Status TERMINATED

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

Texas Tech University Health Science Center

El Paso, Texas, United States

Site Status RECRUITING

The University Of Texas Medical School At Houston - UT Center Of Excellence On Mood Disorders

Houston, Texas, United States

Site Status RECRUITING

Houston Clinical Trials

Houston, Texas, United States

Site Status TERMINATED

Northpointe Psychiatry

Lewisville, Texas, United States

Site Status RECRUITING

Rise Clinical Research, LLC

Missouri City, Texas, United States

Site Status TERMINATED

The University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Neuropsychiatric Associates, Plc

Woodstock, Vermont, United States

Site Status TERMINATED

Carilion Clinic

Roanoke, Virginia, United States

Site Status RECRUITING

Center For Anxiety and Depression

Mercer Island, Washington, United States

Site Status RECRUITING

Seattle Neuropsychiatric Treatment Center

Seattle, Washington, United States

Site Status RECRUITING

Marshall University Joan C. Edwards School of Medicine

Huntington, West Virginia, United States

Site Status RECRUITING

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, United States

Site Status WITHDRAWN

University of Wisconsin

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Laura Yates, BSN

Role: CONTACT

Phone: 281-228-7200

Email: [email protected]

Facility Contacts

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Candace Green

Role: primary

Michael Howell

Role: primary

Bobby Shih

Role: primary

Melissa Escamirosa

Role: primary

Zoe Durkin

Role: primary

Alexis Archer

Role: primary

Yohana Lima

Role: primary

Carlos Bussey

Role: primary

Kailee Kenworthy

Role: primary

Carmen Torres

Role: primary

Elyssa Sisko

Role: primary

Jason R Fritz

Role: primary

Susan Fowler

Role: primary

Sinéad Quinn

Role: primary

Laryssa McCloud

Role: primary

Jennifer Kane

Role: primary

Linda Skaggs

Role: primary

Freeda Baber

Role: primary

Amanda White

Role: primary

Oladele Owasoyo, PhD

Role: primary

Jasli Bonilla

Role: primary

Bryce Lund

Role: primary

Catherine Schuessler

Role: primary

Kayla Thoen

Role: primary

Rachel Johnson

Role: backup

Katherine Fickert

Role: primary

Christopher Sinkler

Role: primary

Mary Beth Haug

Role: primary

Amanda Brouk

Role: primary

Anita Broeker

Role: primary

Lisa Ludwig

Role: primary

Nancy Gilbert, APRN

Role: primary

Michelle Rainka, PharmD

Role: primary

Tatiana Jimenez-Knight

Role: primary

Mariah Garcia

Role: primary

Esha Talati, BS

Role: primary

Lisa Cottone

Role: primary

Anne-Marie Duchemin

Role: primary

Brooke Bhattacharya, MS

Role: primary

Michelle Matukewicz, MHR

Role: primary

Stephanie Terranella

Role: primary

Zoha Babar

Role: backup

Joanna Zheng

Role: primary

Morgan Dancy

Role: primary

Anna Raines Guidry

Role: primary

Tyler Wilson

Role: primary

Tara Upchurch

Role: backup

Hila Abush Segev, PhD

Role: primary

Peter Thompson (PI), MD

Role: primary

Marcela Carbajal Tamez

Role: primary

Asad Islam (PI), MD

Role: primary

Brian Mickey (PI), MD, PhD

Role: primary

Sarah Kwon

Role: backup

Maryann Hollen

Role: primary

David L Dunner (PI), MD

Role: primary

Allison Chen

Role: primary

Suzanne Holroyd, MD

Role: primary

Rick Stauffacher

Role: primary

References

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Aaronson ST, Conway CR, Gordon C, Lee YL, George MS, Zajecka J, Riva-Posse P, Dunner DL, Macaluso M, Rosenquist PB, Mickey BJ, Sheline YI, Hristidis VC, Brown H, Kriedt CL, Tran Q, Bunker MT, Sackeim HA, Rush AJ. Prognostic and Prescriptive Predictors of Treatment Response to Adjunctive VNS Therapy in Major Depressive Disorder: A RECOVER Trial Report. J Clin Psychiatry. 2025 Jul 14;86(3):25m15850. doi: 10.4088/JCP.25m15850.

Reference Type DERIVED
PMID: 40673907 (View on PubMed)

de Leon VC, Allen RM, Quevedo J, Riva-Posse P, Aaronson ST, Berger MA, Zajecka J, Banov MD, Manu LM, Sheline YI, Farrington J, Eloge JC, Beard J, Kriedt CL, Gott BM, Brown H, Bunker MT, Lee YL, Rush AJ, Sackeim HA, Conway CR. Suicide characteristics in patients with marked treatment-resistant major depressive disorder: A RECOVER trial report. J Affect Disord. 2025 Apr 1;374:619-629. doi: 10.1016/j.jad.2024.12.072. Epub 2024 Dec 24.

Reference Type DERIVED
PMID: 39722333 (View on PubMed)

Conway CR, Aaronson ST, Sackeim HA, Duffy W, Stedman M, Quevedo J, Allen RM, Riva-Posse P, Berger MA, Alva G, Malik MA, Dunner DL, Cichowicz I, Luing H, Zajecka J, Nahas Z, Mickey BJ, Kablinger AS, Kriedt CL, Bunker MT, Lee YL, Shy O, Majewski S, Olin B, Tran Q, Rush AJ. Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report. Brain Stimul. 2024 Mar-Apr;17(2):448-459. doi: 10.1016/j.brs.2024.03.016. Epub 2024 Apr 2.

Reference Type DERIVED
PMID: 38574853 (View on PubMed)

Related Links

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https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=292

CMS Decision Memo for Vagus Nerve Stimulation (VNS) for Treatment Resistant Depression

Other Identifiers

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LND-300

Identifier Type: -

Identifier Source: org_study_id