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 (RECOVER)

March 11, 2024 updated by: LivaNova
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

6800

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • Matthew Macaluso, DO
        • Contact:
      • Huntsville, Alabama, United States, 35801
        • Recruiting
        • UAB Huntsville Regional Medical Center
        • Principal Investigator:
          • Richard Shelton
        • Contact:
    • California
      • Burlingame, California, United States, 94010
        • Terminated
        • Access Multi Specialty Medical Clinic, Inc
      • Colton, California, United States, 92324
        • Withdrawn
        • CMB Clinical Trials
      • Costa Mesa, California, United States, 92626
        • Recruiting
        • ATP Clinical Research, Inc.
        • Contact:
        • Principal Investigator:
          • Gustavo Alva, MD
      • La Jolla, California, United States, 92037
        • Recruiting
        • Kaizen Brain Center
        • Principal Investigator:
          • Mohammed Ahmed, MD
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck Hospital of USC
        • Contact:
        • Principal Investigator:
          • Ashraf Elmashat, MD
      • San Diego, California, United States, 92103
        • Active, not recruiting
        • University of California San Diego
      • San Rafael, California, United States, 94901
        • Recruiting
        • SF-CARE, Inc.
        • Contact:
        • Principal Investigator:
          • Jason Bermak, MD
      • Santa Ana, California, United States, 92705
        • Withdrawn
        • Syrentis Clinical Research
    • Florida
      • Boca Raton, Florida, United States, 33431
        • Recruiting
        • Mindful Behavioral Health
        • Contact:
        • Principal Investigator:
          • Ivan Cichowicz, MD
      • Boca Raton, Florida, United States, 33325
        • Terminated
        • Sunrise Research Institute
      • Brooksville, Florida, United States, 34609
        • Terminated
        • Medycal Research, Inc
      • Hialeah, Florida, United States, 33016
        • Recruiting
        • Galiz Research LLC
        • Contact:
        • Principal Investigator:
          • Jose Gamez, MD
      • Largo, Florida, United States, 33770
        • Recruiting
        • Florida Behavioral Psych
        • Principal Investigator:
          • Ashok Patel, MD
        • Contact:
      • Lauderhill, Florida, United States, 33319
        • Withdrawn
        • Segal Trials Corporate
      • Miami, Florida, United States, 33125
        • Withdrawn
        • Central Miami Medical Institute, LLC
      • Miami, Florida, United States, 33135
        • Withdrawn
        • Research Center Of Florida, Inc
      • Miami, Florida, United States, 33135
        • Terminated
        • Clintex Research Group, Inc.
      • Miami Springs, Florida, United States, 33166
        • Withdrawn
        • Ocean Blue Medical Research Center
      • Orlando, Florida, United States, 32803
        • Recruiting
        • APG Research, LLC
        • Principal Investigator:
          • Morteza Nadjafi, MD
        • Contact:
      • Orlando, Florida, United States, 32803
        • Recruiting
        • Nova Psychiatry Inc.
        • Contact:
        • Principal Investigator:
          • David Medina, MD
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Florida Center for TMS
        • Contact:
        • Principal Investigator:
          • Todd Broder, MD
      • Orlando, Florida, United States, 32819
        • Withdrawn
        • Millenia Psychiatry & Research, Inc
      • Pompano Beach, Florida, United States, 33064
        • Terminated
        • Quantum Laboratories Inc.
      • Royal Palm Beach, Florida, United States, 33411
        • Recruiting
        • Advanced Mental Health Care Inc.
        • Contact:
        • Principal Investigator:
          • Aron Tendler, MD
      • Saint Augustine, Florida, United States, 94901
        • Recruiting
        • Florida Center for TMS
        • Contact:
        • Principal Investigator:
          • Heather Luing, MD
      • Tampa, Florida, United States, 33613
      • West Palm Beach, Florida, United States, 33409
        • Terminated
        • Psychiatric Specialty Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Contact:
        • Principal Investigator:
          • Patricio Riva Posse, MD
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Medical College of Georgia, Augusta University
        • Contact:
        • Principal Investigator:
          • Peter Rosenquist, MD
      • Decatur, Georgia, United States, 30030
        • Terminated
        • PACT Atlanta LLC
      • Grayson, Georgia, United States, 30017
        • Withdrawn
        • IACT Health
      • Marietta, Georgia, United States, 30060
        • Recruiting
        • Psych Atlanta
        • Contact:
        • Principal Investigator:
          • Michael Banov, MD
    • Idaho
      • Ammon, Idaho, United States, 83406
        • Withdrawn
        • Pearl Health Clinic
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Principal Investigator:
          • John Zajecka
      • Joliet, Illinois, United States, 60435
        • Terminated
        • Joliet Center for Clinical Research
      • Naperville, Illinois, United States, 60563
        • Recruiting
        • AMR- Baber Research, Inc.
        • Contact:
        • Principal Investigator:
          • Riaz Baber, MD
      • Skokie, Illinois, United States, 60076
        • Recruiting
        • Psychiatric Medicine Associates, LLC
        • Contact:
        • Principal Investigator:
          • John Zajecka, MD
      • Springfield, Illinois, United States, 62794
        • Recruiting
        • Southern Illinois University School of Medicine
        • Contact:
        • Principal Investigator:
          • Jeffrey Bennett, MD
      • Winfield, Illinois, United States, 60910
        • Withdrawn
        • Neuroscience Research Institute
    • Indiana
      • Indianapolis, Indiana, United States, 56268
        • Terminated
        • Advanced Research Institute, Inc.
      • South Bend, Indiana, United States, 46601
        • Recruiting
        • Beacon Medical Group Behavioral Health
        • Contact:
        • Principal Investigator:
          • Suhayl Nasr, MD
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
        • Principal Investigator:
          • Tyler Kjorvestad, MD
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Recruiting
        • Sheppard Pratt Health System, Inc.
        • Principal Investigator:
          • Scott Aaronson, MD
        • Contact:
      • Glen Burnie, Maryland, United States, 21061
        • Withdrawn
        • Clinical Insights
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Cristina Cusin, MD
        • Contact:
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Active, not recruiting
        • Michigan Clinical Research Institute PC
    • Minnesota
      • Minneapolis, Minnesota, United States, 55416
        • Recruiting
        • University of Minnesota
        • Principal Investigator:
          • Ziad Nahas, MD
        • Contact:
          • Maryam Shah Din
          • Phone Number: 952-525-4505
          • Email: ipl@umn.edu
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Recruiting
        • Precise Research Centers
        • Contact:
        • Principal Investigator:
          • Joseph Kwentus, MD
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • Andrew Bishop, MD
        • Principal Investigator:
          • Andrew Bishop, MD
        • Contact:
    • Missouri
      • Columbia, Missouri, United States, 65212
        • Recruiting
        • University of Missouri
        • Contact:
        • Principal Investigator:
          • Muaid Ithman, MD
      • O'Fallon, Missouri, United States, 633668
        • Recruiting
        • Psychiatric Care and Research
        • Contact:
        • Principal Investigator:
          • John Canale, MD
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Barnes-Jewish Hospital
        • Contact:
        • Principal Investigator:
          • Donald Bohnenkamp, MD
      • Saint Louis, Missouri, United States, 63128
        • Recruiting
        • PsychCare Consultants Research
        • Contact:
        • Principal Investigator:
          • Mohd Malik, MD
    • Nebraska
      • Lincoln, Nebraska, United States, 68526
        • Recruiting
        • Alivation Research, LLC
        • Principal Investigator:
          • Walter Duffy, MD
        • Contact:
    • New Hampshire
      • Nashua, New Hampshire, United States, 03060
        • Recruiting
        • Healthy Perspective
        • Contact:
        • Principal Investigator:
          • Hisham Hafez, MD
    • New Jersey
      • Neptune, New Jersey, United States, 07753
        • Withdrawn
        • Jersey Shore University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Withdrawn
        • University of New Mexico - Psychiatric Center
    • New York
      • Amherst, New York, United States, 14226
        • Recruiting
        • Dent Neurological Institute
        • Contact:
        • Principal Investigator:
          • Horacio Capote, MD
      • Buffalo, New York, United States, 14215
        • Withdrawn
        • Erie County Medical Center/State University of New York (SUNY) at Buffalo Affiliate
      • Lewiston, New York, United States, 14092
        • Recruiting
        • Trinity Medical
        • Principal Investigator:
          • Alfred Belen, MD
        • Contact:
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Principal Investigator:
          • James M Murrough, MD
        • Contact:
      • New York, New York, United States, 10019
        • Recruiting
        • Hapworth Research Inc.
        • Contact:
        • Principal Investigator:
          • William Hapworth, MD
      • Staten Island, New York, United States, 10312
        • Withdrawn
        • Richmond Behavioral Associates
      • Stony Brook, New York, United States, 11794
        • Recruiting
        • Stony Brook University Hospital
        • Contact:
        • Principal Investigator:
          • Lucian Manu, MD
      • Syracuse, New York, United States, 13210
        • Terminated
        • State University of New York Upstate Medical University
    • North Carolina
      • Cary, North Carolina, United States, 27519
        • Recruiting
        • The Center for Neuropsychiatry and Brain Stimulation (CNBS) ARC Health
        • Contact:
        • Principal Investigator:
          • Sandeep Vaishnavi
      • Raleigh, North Carolina, United States, 27606
        • Terminated
        • Mindpath Care Centers
      • Winston-Salem, North Carolina, United States, 27103
        • Withdrawn
        • Wake Forest University Health Science
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Withdrawn
        • University Hospitals Case Medical Center
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
        • Contact:
        • Principal Investigator:
          • Kevin Reeves, MD
      • Fairlawn, Ohio, United States, 44333
        • Recruiting
        • Signature Research Associates, Inc.
        • Contact:
        • Principal Investigator:
          • Anand Chaturvedi
      • Garfield Heights, Ohio, United States, 44125
        • Recruiting
        • Charak Center for Health and Wellness
        • Principal Investigator:
          • Rakesh Ranjan, MD
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73109-3834
        • Withdrawn
        • NPC Research
      • Oklahoma City, Oklahoma, United States, 73112
        • Terminated
        • Rivus Wellness & Research Institute
      • Tulsa, Oklahoma, United States, 74135
        • Recruiting
        • University of Oklahoma School of Community Medicine
        • Contact:
        • Principal Investigator:
          • Ondria Gleason, MD
    • Pennsylvania
      • Moosic, Pennsylvania, United States, 18507
        • Recruiting
        • Scranton Medical Institutes
        • Principal Investigator:
          • Matthew Berger, MD
        • Contact:
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19104
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Mark George, MD
    • Tennessee
      • Brentwood, Tennessee, United States, 37027
        • Recruiting
        • Neuroscience and TMS Treatment Center
        • Principal Investigator:
          • Jonathan Becker, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78712
        • Recruiting
        • UT Health Austin, Mulva Clinic for the Neurosciences
        • Contact:
        • Principal Investigator:
          • Julie Farmington, MD
      • Austin, Texas, United States, 78759
        • Terminated
        • BioBehavioral Research of Austin
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern
        • Contact:
        • Principal Investigator:
          • Kala Bailey, MD
      • El Paso, Texas, United States, 79905
        • Recruiting
        • Texas Tech University Health Science Center
        • Contact:
      • Houston, Texas, United States, 77054
        • Recruiting
        • The University Of Texas Medical School At Houston - UT Center Of Excellence On Mood Disorders
        • Principal Investigator:
          • Joao De Quevedo, MD, PhD
        • Contact:
      • Houston, Texas, United States, 77401
        • Terminated
        • Houston Clinical Trials
      • Lewisville, Texas, United States, 75057
      • Missouri City, Texas, United States, 77459
        • Terminated
        • Rise Clinical Research, LLC
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Recruiting
        • The University of Utah
        • Contact:
          • Brian Mickey (PI), MD, PhD
          • Phone Number: 801-587-3297
        • Contact:
    • Vermont
      • Woodstock, Vermont, United States, 05091
        • Recruiting
        • Neuropsychiatric Associates, Plc
        • Contact:
        • Principal Investigator:
          • Susan Smiga, MD
    • Virginia
      • Roanoke, Virginia, United States, 24014
        • Recruiting
        • Carilion Clinic
        • Contact:
        • Principal Investigator:
          • Anita Kablinger, MD
    • Washington
      • Mercer Island, Washington, United States, 98040
        • Recruiting
        • Center For Anxiety and Depression
        • Contact:
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Seattle Neuropsychiatric Treatment Center
        • Principal Investigator:
          • Rebecca Allen, MD
        • Contact:
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Recruiting
        • Marshall University Joan C. Edwards School of Medicine
        • Contact:
        • Principal Investigator:
          • Suzanne Holroyd, MD
      • Morgantown, West Virginia, United States, 26506
        • Withdrawn
        • West Virginia Clinical and Translational Science Institute
    • Wisconsin
      • Madison, Wisconsin, United States, 53719

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active
Group will have VNS activated 2 weeks post implant.
Device: Vagus Nerve Stimulation (VNS)
VNS is an implantable device that delivers stimulation to the vagal nerve.
Other Names:
  • VNS
Sham Comparator: 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.
Device: Vagus Nerve Stimulation (VNS)
VNS is an implantable device that delivers stimulation to the vagal nerve.
Other Names:
  • VNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months post randomization
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.
Baseline up to 12 Months
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.
Baseline up to 12 Months
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.
Baseline up to 12 Months
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
Baseline up to 12 Months
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).
Baseline up to 12 Months
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).
Baseline up to 12 Months
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).
Baseline up to 12 Months
Assess all Adverse Events
Time Frame: Implant to 12 Months
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
Time Frame: Baseline to 12 Months
Baseline to 12 Months
Health Outcome Scale (EQ-5D-L) Changes in scores over time
Time Frame: Baseline to 12 Months
Baseline to 12 Months
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.
12 months post randomization
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
Implant to 12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

LivaNova

Investigators

  • Principal Investigator: Charles Conway, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2019

Primary Completion (Estimated)

February 28, 2028

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

March 21, 2019

First Submitted That Met QC Criteria

March 21, 2019

First Posted (Actual)

March 25, 2019

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LND-300

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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