NCT03887715 · LivaNova
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)
What this study is about
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.
View original scientific description
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.
Interventions
DEVICE
Vagus Nerve Stimulation (VNS)
VNS is an implantable device that delivers stimulation to the vagal nerve.
Primary outcome measures
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.
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.
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.
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.
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
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).
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).
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).
Assess all Adverse Events
Time frame: Implant to 12 Months
All adverse events, with a focus on device or procedure-related serious adverse events.
WHO Disability Assessment Schedule (WHODAS) Changes in scores over time
Time frame: Baseline to 12 Months
Health Outcome Scale (EQ-5D-L) Changes in scores over time
Time frame: 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.
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Birmingham, Alabama
- Huntsville, Alabama
- Burlingame, California
- Colton, California
- Costa Mesa, California
- La Jolla, California
- Los Angeles, California
- San Diego, California
- San Rafael, California
- Santa Ana, California
- Boca Raton, Florida
- Brooksville, Florida
And 76 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 15, 2026 · Source of record for eligibility and locations