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

Обзор

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.

Подробное описание

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).

Вмешательства

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

Первичные конечные точки

• Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response [Срок оценки: 12 months post randomization]
• Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission [Срок оценки: Baseline up to 12 Months]
• Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission [Срок оценки: Baseline up to 12 Months]
• Assess all Adverse Events [Срок оценки: Implant to 12 Months]
• WHO Disability Assessment Schedule (WHODAS) Changes in scores over time [Срок оценки: Baseline to 12 Months]

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 101 центр

• University of Alabama at Birmingham — Birmingham
• UAB Huntsville Regional Medical Center — Huntsville
• Access Multi Specialty Medical Clinic, Inc — Burlingame
• CMB Clinical Trials — Colton
• ATP Clinical Research, Inc. — Costa Mesa
• Kaizen Brain Center — La Jolla
• Keck Hospital of USC — Los Angeles
• University of California San Diego — San Diego
• … и ещё 93 центра

Публикации

• Hristidis VC, De Leon V, Van Der Vaart AD, Sackeim HA, Rush AJ, Aaronson ST, Bunker MT, Allen RM, Sheline Y, Nahas Z, Dunner DL, Gott BM, Lee YC, Gordon C, Tran Q, Shy O, Quevedo J, Riva-Posse P, Zajecka J, Mickey BJ, Duffy W, Kriedt CL, Oquendo MA, Conway CR. Impact of Vagus Nerve Stimulation on Suicidal Ideation in Markedly Treatment-Resistant Major Depression: A RECOVER Study Report. J Clin Psy PMID 42447264
• Conway CR, Rush AJ, Aaronson ST, Bunker MT, Gordon C, George MS, Riva-Posse P, Allen RM, Nahas Z, Kriedt CL, Zajecka J, Dunner DL, Quevedo J, Sheline Y, Duffy W, Mickey BJ, Stedman M, Alva G, Manu L, Tran Q, Zorumski CF, Macaluso M, Banov M, Cusin C, Bennett JI, Brown H, Way J, Shy O, Lee YL, McAllister-Williams RH, McIntyre RS, Sackeim HA. Durability of the benefit of vagus nerve stimulation in m PMID 41529263
• Aaronson ST, Conway CR, Gordon C, Lee YL, George MS, Zajecka J, Riva-Posse P, Dunner DL, Macaluso M, Rosenquist PB, Mickey BJ, Sheline YI, Hristidis VC, Brown H, Kriedt CL, Tran Q, Bunker MT, Sackeim HA, Rush AJ. Prognostic and Prescriptive Predictors of Treatment Response to Adjunctive VNS Therapy in Major Depressive Disorder: A RECOVER Trial Report. J Clin Psychiatry. 2025 Jul 14;86(3):25m15850. PMID 40673907
• de Leon VC, Allen RM, Quevedo J, Riva-Posse P, Aaronson ST, Berger MA, Zajecka J, Banov MD, Manu LM, Sheline YI, Farrington J, Eloge JC, Beard J, Kriedt CL, Gott BM, Brown H, Bunker MT, Lee YL, Rush AJ, Sackeim HA, Conway CR. Suicide characteristics in patients with marked treatment-resistant major depressive disorder: A RECOVER trial report. J Affect Disord. 2025 Apr 1;374:619-629. doi: 10.1016/j PMID 39722333
• Conway CR, Aaronson ST, Sackeim HA, Duffy W, Stedman M, Quevedo J, Allen RM, Riva-Posse P, Berger MA, Alva G, Malik MA, Dunner DL, Cichowicz I, Luing H, Zajecka J, Nahas Z, Mickey BJ, Kablinger AS, Kriedt CL, Bunker MT, Lee YL, Shy O, Majewski S, Olin B, Tran Q, Rush AJ. Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: PMID 38574853

Идентификаторы

NCT: NCT03887715 · LND-300

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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