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

NCT03887715 | Recruiting DMC FDA Device

• 1 other identifier: LND-300
• Study Type: interventional
• Target: 6,800
• Locations: 1 country
• Sites: 98

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.

Conditions

Treatment Resistant Depression

Keywords

VNS; Depression; TRD

Outcome Measures

Primary Outcomes (13)

• Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response

  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.

  12 months post randomization

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

  Time from randomization to the first observed MADRS response.

  Baseline up to 12 Months

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

  Time from randomization to the first observed MADRS remission.

  Baseline up to 12 Months

• Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response

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

  Baseline up to 12 Months

• Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission

  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

  Baseline up to 12 Months

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

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

  Baseline up to 12 Months

• Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission

  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).

  Baseline up to 12 Months

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

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

  Baseline up to 12 Months

• Assess all Adverse Events

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

  Implant to 12 Months

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

  Baseline to 12 Months

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

  Baseline to 12 Months

• Clinical Global Impressions Scale - Improvement (CGI-I) Response

  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.

  12 months post randomization

• Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality

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

  Implant to 12 Months

Study Arms (2)

Active

ACTIVE COMPARATOR

Group will have VNS activated 2 weeks post implant.

Device: Vagus Nerve Stimulation (VNS)

Control

SHAM COMPARATOR

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

Device: Vagus Nerve Stimulation (VNS)

Interventions

Vagus Nerve Stimulation (VNS) DEVICE

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

Also known as: VNS

Active; Control

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LivaNova: lead

Study Sites (98)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

UAB Huntsville Regional Medical Center

Huntsville, Alabama, 35801, United States

RECRUITING

Access Multi Specialty Medical Clinic, Inc

Burlingame, California, 94010, United States

TERMINATED

CMB Clinical Trials

Colton, California, 92324, United States

WITHDRAWN

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

RECRUITING

Kaizen Brain Center

La Jolla, California, 92037, United States

RECRUITING

Keck Hospital of USC

Los Angeles, California, 90033, United States

RECRUITING

University of California San Diego

San Diego, California, 92103, United States

ACTIVE NOT RECRUITING

SF-CARE, Inc.

San Rafael, California, 94901, United States

TERMINATED

Syrentis Clinical Research

Santa Ana, California, 92705, United States

WITHDRAWN

Sunrise Research Institute

Boca Raton, Florida, 33325, United States

TERMINATED

Mindful Behavioral Health

Boca Raton, Florida, 33431, United States

RECRUITING

Medycal Research, Inc

Brooksville, Florida, 34609, United States

TERMINATED

Galiz Research LLC

Hialeah, Florida, 33016, United States

RECRUITING

Florida Behavioral Psych

Largo, Florida, 33770, United States

RECRUITING

Segal Trials Corporate

Lauderhill, Florida, 33319, United States

WITHDRAWN

Central Miami Medical Institute, LLC

Miami, Florida, 33125, United States

WITHDRAWN

Clintex Research Group, Inc.

Miami, Florida, 33135, United States

TERMINATED

Research Center Of Florida, Inc

Miami, Florida, 33135, United States

WITHDRAWN

Ocean Blue Medical Research Center

Miami Springs, Florida, 33166, United States

WITHDRAWN

APG Research, LLC

Orlando, Florida, 32803, United States

RECRUITING

Nova Psychiatry Inc.

Orlando, Florida, 32803, United States

RECRUITING

Florida Center for TMS

Orlando, Florida, 32806, United States

TERMINATED

Millenia Psychiatry & Research, Inc

Orlando, Florida, 32819, United States

WITHDRAWN

Quantum Laboratories Inc.

Pompano Beach, Florida, 33064, United States

TERMINATED

Advanced Mental Health Care Inc.

Royal Palm Beach, Florida, 33411, United States

RECRUITING

Florida Center for TMS

Saint Augustine, Florida, 94901, United States

RECRUITING

Stedman Clinical Trials

Tampa, Florida, 33613, United States

RECRUITING

Psychiatric Specialty Center

West Palm Beach, Florida, 33409, United States

TERMINATED

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Medical College of Georgia, Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

PACT Atlanta LLC

Decatur, Georgia, 30030, United States

TERMINATED

IACT Health

Grayson, Georgia, 30017, United States

WITHDRAWN

Psych Atlanta

Marietta, Georgia, 30060, United States

RECRUITING

Pearl Health Clinic

Ammon, Idaho, 83406, United States

WITHDRAWN

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Joliet Center For Clinical Research

Joliet, Illinois, 60435, United States

TERMINATED

AMR- Baber Research, Inc.

Naperville, Illinois, 60563, United States

RECRUITING

Psychiatric Medicine Associates, LLC

Skokie, Illinois, 60076, United States

RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, 62794, United States

RECRUITING

Neuroscience Research Institute

Winfield, Illinois, 60910, United States

WITHDRAWN

Advanced Research Institute, Inc.

Indianapolis, Indiana, 56268, United States

TERMINATED

Beacon Medical Group Behavioral Health

South Bend, Indiana, 46601, United States

ACTIVE NOT RECRUITING

University Of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

Sheppard Pratt Health System, Inc.

Baltimore, Maryland, 21204, United States

RECRUITING

Clinical Insights

Glen Burnie, Maryland, 21061, United States

WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48105, United States

ACTIVE NOT RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55416, United States

RECRUITING

Precise Research Centers

Flowood, Mississippi, 39232, United States

RECRUITING

Andrew Bishop, MD

Jackson, Mississippi, 39216, United States

TERMINATED

University of Missouri

Columbia, Missouri, 65212, United States

RECRUITING

Psychiatric Care and Research

O'Fallon, Missouri, 633668, United States

RECRUITING

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

RECRUITING

PsychCare Consultants Research

St Louis, Missouri, 63128, United States

RECRUITING

Alivation Research, LLC

Lincoln, Nebraska, 68526, United States

RECRUITING

Healthy Perspective

Nashua, New Hampshire, 03060, United States

RECRUITING

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

WITHDRAWN

University of New Mexico - Psychiatric Center

Albuquerque, New Mexico, 87102, United States

WITHDRAWN

Dent Neurological Institute

Amherst, New York, 14226, United States

RECRUITING

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

Buffalo, New York, 14215, United States

WITHDRAWN

Trinity Medical

Lewiston, New York, 14092, United States

RECRUITING

Hapworth Research Inc.

New York, New York, 10019, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

WITHDRAWN

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

TERMINATED

State University Of New York Upstate Medical University

Syracuse, New York, 13210, United States

TERMINATED

ManuMind Interventional Psychiatry

Woodbury, New York, 11797, United States

RECRUITING

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

Cary, North Carolina, 27519, United States

TERMINATED

Mindpath Care Centers

Raleigh, North Carolina, 27606, United States

TERMINATED

Wake Forest University Health Science

Winston-Salem, North Carolina, 27103, United States

WITHDRAWN

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

WITHDRAWN

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Signature Research Associates, Inc.

Fairlawn, Ohio, 44333, United States

ACTIVE NOT RECRUITING

Charak Center for Health and Wellness

Garfield Heights, Ohio, 44125, United States

RECRUITING

NPC Research

Oklahoma City, Oklahoma, 73109-3834, United States

WITHDRAWN

Rivus Wellness & Research Institute

Oklahoma City, Oklahoma, 73112, United States

TERMINATED

University of Oklahoma School of Community Medicine

Tulsa, Oklahoma, 74135, United States

RECRUITING

Scranton Medical Institutes

Moosic, Pennsylvania, 18507, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Neuroscience and TMS Treatment Center

Brentwood, Tennessee, 37027, United States

RECRUITING

UT Health Austin, Mulva Clinic for the Neurosciences

Austin, Texas, 78712, United States

RECRUITING

BioBehavioral Research of Austin

Austin, Texas, 78759, United States

TERMINATED

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

Texas Tech University Health Science Center

El Paso, Texas, 79905, United States

RECRUITING

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

Houston, Texas, 77054, United States

RECRUITING

Houston Clinical Trials

Houston, Texas, 77401, United States

TERMINATED

Northpointe Psychiatry

Lewisville, Texas, 75057, United States

RECRUITING

Rise Clinical Research, LLC

Missouri City, Texas, 77459, United States

TERMINATED

The University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

Neuropsychiatric Associates, Plc

Woodstock, Vermont, 05091, United States

TERMINATED

Carilion Clinic

Roanoke, Virginia, 24014, United States

RECRUITING

Center For Anxiety and Depression

Mercer Island, Washington, 98040, United States

RECRUITING

Seattle Neuropsychiatric Treatment Center

Seattle, Washington, 98104, United States

RECRUITING

Marshall University Joan C. Edwards School of Medicine

Huntington, West Virginia, 25701, United States

RECRUITING

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, 26506, United States

WITHDRAWN

University of Wisconsin

Madison, Wisconsin, 53719, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 40673907 DERIVED

• 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.

  PMID: 39722333 DERIVED

• 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.

  PMID: 38574853 DERIVED

Related Links

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

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Charles Conway, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Yates, BSN

CONTACT

281-228-7200; laura.yates@livanova.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1:1 randomization of active stimulation vs. no stimulation for 12 months post randomization.

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: March 25, 2019
• Study Start: September 26, 2019
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (98)