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

Treatment Resistant Depression Clinical Trial

— RECOVER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03887715
• Other study ID #: LND-300
• Status: Recruiting
• Phase: N/A
• Start date: September 26, 2019
• Est. completion date: December 31, 2030

Study information

• Verified date: March 2024
• Source: LivaNova
• Contact: Laura Yates, BSN
• Phone: 281-228-7200
• Email: laura.yates[@]livanova.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 6800
• Est. completion date: December 31, 2030
• Est. primary completion date: February 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

Device:
• Vagus Nerve Stimulation (VNS)
VNS is an implantable device that delivers stimulation to the vagal nerve.

Locations

Country	Name	City	State
United States	University of New Mexico - Psychiatric Center	Albuquerque	New Mexico
United States	Dent Neurological Institute	Amherst	New York
United States	Pearl Health Clinic	Ammon	Idaho
United States	Michigan Clinical Research Institute PC	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Medical College of Georgia, Augusta University	Augusta	Georgia
United States	BioBehavioral Research of Austin	Austin	Texas
United States	UT Health Austin, Mulva Clinic for the Neurosciences	Austin	Texas
United States	Sheppard Pratt Health System, Inc.	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Mindful Behavioral Health	Boca Raton	Florida
United States	Sunrise Research Institute	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Neuroscience and TMS Treatment Center	Brentwood	Tennessee
United States	Medycal Research, Inc	Brooksville	Florida
United States	Erie County Medical Center/State University of New York (SUNY) at Buffalo Affiliate	Buffalo	New York
United States	Access Multi Specialty Medical Clinic, Inc	Burlingame	California
United States	The Center for Neuropsychiatry and Brain Stimulation (CNBS) ARC Health	Cary	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	CMB Clinical Trials	Colton	California
United States	University of Missouri	Columbia	Missouri
United States	The Ohio State University	Columbus	Ohio
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	University of Texas Southwestern	Dallas	Texas
United States	PACT Atlanta LLC	Decatur	Georgia
United States	Texas Tech University Health Science Center	El Paso	Texas
United States	Signature Research Associates, Inc.	Fairlawn	Ohio
United States	Precise Research Centers	Flowood	Mississippi
United States	Charak Center for Health and Wellness	Garfield Heights	Ohio
United States	Clinical Insights	Glen Burnie	Maryland
United States	IACT Health	Grayson	Georgia
United States	Galiz Research LLC	Hialeah	Florida
United States	Houston Clinical Trials	Houston	Texas
United States	The University Of Texas Medical School At Houston - UT Center Of Excellence On Mood Disorders	Houston	Texas
United States	Marshall University Joan C. Edwards School of Medicine	Huntington	West Virginia
United States	UAB Huntsville Regional Medical Center	Huntsville	Alabama
United States	Advanced Research Institute, Inc.	Indianapolis	Indiana
United States	Andrew Bishop, MD	Jackson	Mississippi
United States	Joliet Center For Clinical Research	Joliet	Illinois
United States	University Of Kansas Cancer Center	Kansas City	Kansas
United States	Kaizen Brain Center	La Jolla	California
United States	Florida Behavioral Psych	Largo	Florida
United States	Segal Trials Corporate	Lauderhill	Florida
United States	Trinity Medical	Lewiston	New York
United States	Northpointe Psychiatry	Lewisville	Texas
United States	Alivation Research, LLC	Lincoln	Nebraska
United States	Keck Hospital of USC	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Psych Atlanta	Marietta	Georgia
United States	Center For Anxiety and Depression	Mercer Island	Washington
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	Ocean Blue Medical Research Center	Miami Springs	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Rise Clinical Research, LLC	Missouri City	Texas
United States	Scranton Medical Institutes	Moosic	Pennsylvania
United States	West Virginia Clinical and Translational Science Institute	Morgantown	West Virginia
United States	AMR- Baber Research, Inc.	Naperville	Illinois
United States	Healthy Perspective	Nashua	New Hampshire
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Hapworth Research Inc.	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Psychiatric Care and Research	O'Fallon	Missouri
United States	NPC Research	Oklahoma City	Oklahoma
United States	Rivus Wellness & Research Institute	Oklahoma City	Oklahoma
United States	APG Research, LLC	Orlando	Florida
United States	Florida Center for TMS	Orlando	Florida
United States	Millenia Psychiatry & Research, Inc	Orlando	Florida
United States	Nova Psychiatry Inc.	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Quantum Laboratories Inc.	Pompano Beach	Florida
United States	Mindpath Care Centers	Raleigh	North Carolina
United States	Carilion Clinic	Roanoke	Virginia
United States	Advanced Mental Health Care Inc.	Royal Palm Beach	Florida
United States	Florida Center for TMS	Saint Augustine	Florida
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	The University of Utah	Salt Lake City	Utah
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	Seattle Neuropsychiatric Treatment Center	Seattle	Washington
United States	Psychiatric Medicine Associates, LLC	Skokie	Illinois
United States	Beacon Medical Group Behavioral Health	South Bend	Indiana
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Stony Brook University Hospital	Stony Brook	New York
United States	State University Of New York Upstate Medical University	Syracuse	New York
United States	Stedman Clinical Trials	Tampa	Florida
United States	University of Oklahoma School of Community Medicine	Tulsa	Oklahoma
United States	Psychiatric Specialty Center	West Palm Beach	Florida
United States	Neuroscience Research Institute	Winfield	Illinois
United States	Wake Forest University Health Science	Winston-Salem	North Carolina
United States	Neuropsychiatric Associates, Plc	Woodstock	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
LivaNova

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response	Time from randomization to the first observed MADRS response.	Baseline up to 12 Months
Primary	Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission	Time from randomization to the first observed MADRS remission.	Baseline up to 12 Months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Assess all Adverse Events	All adverse events, with a focus on device or procedure-related serious adverse events.	Implant to 12 Months
Primary	WHO Disability Assessment Schedule (WHODAS) Changes in scores over time		Baseline to 12 Months
Primary	Health Outcome Scale (EQ-5D-L) Changes in scores over time		Baseline to 12 Months
Primary	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
Primary	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

External Links

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