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
- Conditions
- Treatment Resistant Depression
- Interventions
- Device: Vagus Nerve Stimulation (VNS)
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 6800
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.
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
- Arm && Interventions
Group Intervention Description Active Vagus Nerve Stimulation (VNS) Group will have VNS activated 2 weeks post implant. Control Vagus Nerve Stimulation (VNS) Group will be implanted with VNS but device is not activated for the first 12 months. After 12 months, this group can receive stimulation.
- Primary Outcome Measures
Name Time Method Assess all Adverse Events Implant to 12 Months All adverse events, with a focus on device or procedure-related serious adverse events.
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.
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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (96)
Millenia Psychiatry & Research, Inc
🇺🇸Orlando, Florida, United States
Quantum Laboratories Inc.
🇺🇸Pompano Beach, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
Andrew Bishop, MD
🇺🇸Jackson, Mississippi, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of New Mexico - Psychiatric Center
🇺🇸Albuquerque, New Mexico, United States
Michigan Clinical Research Institute PC
🇺🇸Ann Arbor, Michigan, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
PsychCare Consultants Research
🇺🇸Saint Louis, Missouri, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
Alivation Research, LLC
🇺🇸Lincoln, Nebraska, United States
Healthy Perspective
🇺🇸Nashua, New Hampshire, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Dent Neurological Institute
🇺🇸Amherst, New York, United States
Erie County Medical Center/State University of New York (SUNY) at Buffalo Affiliate
🇺🇸Buffalo, New York, United States
Trinity Medical
🇺🇸Lewiston, New York, United States
Hapworth Research Inc.
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
State University Of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
The Center for Neuropsychiatry and Brain Stimulation (CNBS) ARC Health
🇺🇸Cary, North Carolina, United States
Mindpath Care Centers
🇺🇸Raleigh, North Carolina, United States
Wake Forest University Health Science
🇺🇸Winston-Salem, North Carolina, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Neuroscience and TMS Treatment Center
🇺🇸Brentwood, Tennessee, United States
UT Health Austin, Mulva Clinic for the Neurosciences
🇺🇸Austin, Texas, United States
BioBehavioral Research of Austin
🇺🇸Austin, Texas, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Texas Tech University Health Science Center
🇺🇸El Paso, Texas, United States
The University Of Texas Medical School At Houston - UT Center Of Excellence On Mood Disorders
🇺🇸Houston, Texas, United States
Houston Clinical Trials
🇺🇸Houston, Texas, United States
Northpointe Psychiatry
🇺🇸Lewisville, Texas, United States
Rise Clinical Research, LLC
🇺🇸Missouri City, Texas, United States
The University of Utah
🇺🇸Salt Lake City, Utah, United States
Neuropsychiatric Associates, Plc
🇺🇸Woodstock, Vermont, United States
Carilion Clinic
🇺🇸Roanoke, Virginia, United States
Center For Anxiety and Depression
🇺🇸Mercer Island, Washington, United States
Seattle Neuropsychiatric Treatment Center
🇺🇸Seattle, Washington, United States
Marshall University Joan C. Edwards School of Medicine
🇺🇸Huntington, West Virginia, United States
West Virginia Clinical and Translational Science Institute
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, 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
Sunrise Research Institute
🇺🇸Boca Raton, Florida, United States
Mindful Behavioral Health
🇺🇸Boca Raton, Florida, United States
Medycal Research, Inc
🇺🇸Brooksville, Florida, United States
Galiz Research LLC
🇺🇸Hialeah, Florida, United States
Florida Behavioral Psych
🇺🇸Largo, Florida, United States
Segal Trials Corporate
🇺🇸Lauderhill, Florida, United States
Ocean Blue Medical Research Center
🇺🇸Miami Springs, Florida, United States
Central Miami Medical Institute, LLC
🇺🇸Miami, Florida, United States
Clintex Research Group, Inc.
🇺🇸Miami, Florida, United States
Research Center Of Florida, Inc
🇺🇸Miami, Florida, United States
APG Research, LLC
🇺🇸Orlando, Florida, United States
Nova Psychiatry Inc.
🇺🇸Orlando, Florida, United States
Florida Center for TMS
🇺🇸Saint Augustine, Florida, United States
Advanced Mental Health Care Inc.
🇺🇸Royal Palm Beach, Florida, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
Psychiatric Specialty Center
🇺🇸West Palm Beach, Florida, United States
Medical College of Georgia, Augusta University
🇺🇸Augusta, Georgia, United States
PACT Atlanta LLC
🇺🇸Decatur, Georgia, United States
IACT Health
🇺🇸Grayson, Georgia, United States
Psych Atlanta
🇺🇸Marietta, Georgia, United States
Pearl Health Clinic
🇺🇸Ammon, Idaho, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Joliet Center For Clinical Research
🇺🇸Joliet, Illinois, United States
AMR- Baber Research, Inc.
🇺🇸Naperville, Illinois, United States
Psychiatric Medicine Associates, LLC
🇺🇸Skokie, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Neuroscience Research Institute
🇺🇸Winfield, Illinois, United States
Advanced Research Institute, Inc.
🇺🇸Indianapolis, Indiana, United States
Beacon Medical Group Behavioral Health
🇺🇸South Bend, Indiana, United States
University Of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Sheppard Pratt Health System, Inc.
🇺🇸Baltimore, Maryland, United States
Clinical Insights
🇺🇸Glen Burnie, Maryland, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Psychiatric Care and Research
🇺🇸O'Fallon, Missouri, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Signature Research Associates, Inc.
🇺🇸Fairlawn, Ohio, United States
Charak Center for Health and Wellness
🇺🇸Garfield Heights, Ohio, United States
NPC Research
🇺🇸Oklahoma City, Oklahoma, United States
Rivus Wellness & Research Institute
🇺🇸Oklahoma City, Oklahoma, United States
University of Oklahoma School of Community Medicine
🇺🇸Tulsa, Oklahoma, United States
Scranton Medical Institutes
🇺🇸Moosic, Pennsylvania, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UAB Huntsville Regional Medical Center
🇺🇸Huntsville, Alabama, United States