Treatment Resistant Depression
Conditions
Keywords
VNS, Depression, TRD
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).
Interventions
VNS is an implantable device that delivers stimulation to the vagal nerve.
Sponsors
LivaNova
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Central Rater and sponsor are blinded in the RCT phase. Sites will need to have an unblinded programmer who is only programming the device and not collecting outcomes data.
Intervention model description
1:1 randomization of active stimulation vs. no stimulation for 12 months post randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 response | Baseline up to 12 Months | Time from randomization to the first observed MADRS response. |
| 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) 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. |
| 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 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). |
| 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). |
| Assess all Adverse Events | 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 | Baseline to 12 Months | — |
| Health Outcome Scale (EQ-5D-L) Changes in scores over time | Baseline to 12 Months | — |
| 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. |
| 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 |
Countries
United States
Contacts
CONTACTLaura Yates, BSN
PRINCIPAL_INVESTIGATORCharles Conway, MD
Washington University School of Medicine
Outcome results
None listed