Clinical trial NCT03887715: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: VNS
Depression
TRD
Lead sponsor: LivaNova
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 6800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization of active stimulation vs. no stimulation for 12 months post randomization.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response
timeFrame: 12 months post randomization
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission
timeFrame: Baseline up to 12 Months
measure: Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission
timeFrame: Baseline up to 12 Months
measure: Assess all Adverse Events
timeFrame: Implant to 12 Months
measure: WHO Disability Assessment Schedule (WHODAS) Changes in scores over time
timeFrame: Baseline to 12 Months
measure: Health Outcome Scale (EQ-5D-L) Changes in scores over time
timeFrame: Baseline to 12 Months
measure: Clinical Global Impressions Scale - Improvement (CGI-I) Response
timeFrame: 12 months post randomization
measure: Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality
timeFrame: Implant to 12 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Huntsville
country: United States
facility: UAB Huntsville Regional Medical Center
state: Alabama
city: Burlingame
country: United States
facility: Access Multi Specialty Medical Clinic, Inc
state: California
city: Colton
country: United States
facility: CMB Clinical Trials
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: La Jolla
country: United States
facility: Kaizen Brain Center
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Rafael
country: United States
facility: SF-CARE, Inc.
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Boca Raton
country: United States
facility: Sunrise Research Institute
state: Florida
city: Boca Raton
country: United States
facility: Mindful Behavioral Health
state: Florida
city: Brooksville
country: United States
facility: Medycal Research, Inc
state: Florida
city: Hialeah
country: United States
facility: Galiz Research LLC
state: Florida
city: Largo
country: United States
facility: Florida Behavioral Psych
state: Florida
city: Lauderhill
country: United States
facility: Segal Trials Corporate
state: Florida
city: Miami Springs
country: United States
facility: Ocean Blue Medical Research Center
state: Florida
city: Miami
country: United States
facility: Central Miami Medical Institute, LLC
state: Florida
city: Miami
country: United States
facility: Clintex Research Group, Inc.
state: Florida
city: Miami
country: United States
facility: Research Center Of Florida, Inc
state: Florida
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Orlando
country: United States
facility: Nova Psychiatry Inc.
state: Florida
city: Orlando
country: United States
facility: Florida Center for TMS
state: Florida
city: Orlando
country: United States
facility: Millenia Psychiatry & Research, Inc
state: Florida
city: Pompano Beach
country: United States
facility: Quantum Laboratories Inc.
state: Florida
city: Royal Palm Beach
country: United States
facility: Advanced Mental Health Care Inc.
state: Florida
city: Saint Augustine
country: United States
facility: Florida Center for TMS
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Psychiatric Specialty Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia, Augusta University
state: Georgia
city: Decatur
country: United States
facility: PACT Atlanta LLC
state: Georgia
city: Grayson
country: United States
facility: IACT Health
state: Georgia
city: Marietta
country: United States
facility: Psych Atlanta
state: Georgia
city: Ammon
country: United States
facility: Pearl Health Clinic
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Center For Clinical Research
state: Illinois
city: Naperville
country: United States
facility: AMR- Baber Research, Inc.
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates, LLC
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Winfield
country: United States
facility: Neuroscience Research Institute
state: Illinois
city: Indianapolis
country: United States
facility: Advanced Research Institute, Inc.
state: Indiana
city: South Bend
country: United States
facility: Beacon Medical Group Behavioral Health
state: Indiana
city: Kansas City
country: United States
facility: University Of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Sheppard Pratt Health System, Inc.
state: Maryland
city: Glen Burnie
country: United States
facility: Clinical Insights
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute PC
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Jackson
country: United States
facility: Andrew Bishop, MD
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: O'Fallon
country: United States
facility: Psychiatric Care and Research
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Lincoln
country: United States
facility: Alivation Research, LLC
state: Nebraska
city: Nashua
country: United States
facility: Healthy Perspective
state: New Hampshire
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico - Psychiatric Center
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center/State University of New York (SUNY) at Buffalo Affiliate
state: New York
city: Lewiston
country: United States
facility: Trinity Medical
state: New York
city: New York
country: United States
facility: Hapworth Research Inc.
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Syracuse
country: United States
facility: State University Of New York Upstate Medical University
state: New York
city: Cary
country: United States
facility: The Center for Neuropsychiatry and Brain Stimulation (CNBS) ARC Health
state: North Carolina
city: Raleigh
country: United States
facility: Mindpath Care Centers
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Science
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Fairlawn
country: United States
facility: Signature Research Associates, Inc.
state: Ohio
city: Garfield Heights
country: United States
facility: Charak Center for Health and Wellness
state: Ohio
city: Oklahoma City
country: United States
facility: NPC Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Rivus Wellness & Research Institute
state: Oklahoma
city: Tulsa
country: United States
facility: University of Oklahoma School of Community Medicine
state: Oklahoma
city: Moosic
country: United States
facility: Scranton Medical Institutes
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Brentwood
country: United States
facility: Neuroscience and TMS Treatment Center
state: Tennessee
city: Austin
country: United States
facility: UT Health Austin, Mulva Clinic for the Neurosciences
state: Texas
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: Houston
country: United States
facility: The University Of Texas Medical School At Houston - UT Center Of Excellence On Mood Disorders
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials
state: Texas
city: Lewisville
country: United States
facility: Northpointe Psychiatry
state: Texas
city: Missouri City
country: United States
facility: Rise Clinical Research, LLC
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah
state: Utah
city: Woodstock
country: United States
facility: Neuropsychiatric Associates, Plc
state: Vermont
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Mercer Island
country: United States
facility: Center For Anxiety and Depression
state: Washington
city: Seattle
country: United States
facility: Seattle Neuropsychiatric Treatment Center
state: Washington
city: Huntington
country: United States
facility: Marshall University Joan C. Edwards School of Medicine
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia Clinical and Translational Science Institute
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Washington University School of Medicine
name: Charles Conway, MD
role: PRINCIPAL_INVESTIGATOR
References: