A Study to Assess Effectiveness and Efficiency of VNS Therapy in Patients With Difficult to Treat Depression.

NCT03320304 | Recruiting FDA Device

• 1 other identifier: LNN800
• Study Type: observational
• Target: 500
• Locations: 4 countries
• Sites: 18

Brief Summary

The primary objective of this study is to assess short, mid and long-term clinical outcomes in patients with difficult to treat depression (such as patients with treatment resistant depression) treated with Vagus Nerve Stimulation (VNS) Therapy as adjunctive therapy.

Conditions

Treatment Resistant Depression

Keywords

Difficult to Treat Depression; TRD; VNS Therapy; Vagus Nerve Stimulation; VNS

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of this study is response defined as reduction in Montgomery Åsberg Depression Rating Scale (MADRS) total score of at least 50% from baseline to 12 months post implant.

  MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Higher MADRS score indicates more severe depression. A 'Responder' is a subject that achieved ≥ 50% reduction from baseline in MADRS total score at the M12 assessment. A 'Non-Responder' is any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at the M12 assessment. No formal hypothesis testing is presented; all the proposed statistical tests are descriptive in nature. The Primary endpoint analysis as defined above will be done only on patients that are enrolled while in a major depressive episode (MDE); the cut off point for current MDE at time of implant will be a MADRS score of 20. For the patients with a MADRS score below 20 at time of enrollment, only the continuous change in MADRS can be described (as the MADRS can only worsen or stay the same).

  12 months

Secondary Outcomes (16)

• Duration of response

  through study completion, an average of 4 years

• Change in MADRS

  through study completion, an average of 4 years

• Cumulative response

  through study completion, an average of 4 years

• Cumulative remission

  through study completion, an average of 4 years

• Changes in depression score As measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR).

  through study completion, an average of 4 years

Study Arms (1)

Vagal Nerve Simulation (VNS) Therapy

The aim of this study is to include patients with difficult to treat depression from a global "real world" (standard of care) population who are referred for treatment with VNS Therapy.

Device: Vagal Nerve Simulation (VNS) Therapy

Interventions

Vagal Nerve Simulation (VNS) Therapy DEVICE

A VNS Therapy System used for vagus nerve stimulation and consisting of an implantable VNS Therapy generator, lead, and external programming system.

Vagal Nerve Simulation (VNS) Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population under study comprises a real-world patient population with difficult to treat depression: patients diagnosed with unipolar or bipolar disorder with chronic or recurrent depression who fail to achieve an adequate response to standard psychiatric management. The diagnosis of depression and comorbid disorders will be determined based on the Mini International Neuropsychiatric Interview (MINI).

You may qualify if:

• Be at least 18 years of age.
• Have a documented primary diagnosis of chronic (\>2 years) or recurrent (2 or more prior episodes) major depressive episode that has not adequately responded to an adequate number of antidepressant treatments, as per local medical standards. This diagnosis must be confirmed using the MINI.
• Provide written Ethics Committee (EC) or Institutional Review Board (IRB) approved informed consent and Health Insurance Portability and Accountability Act (HIPAA, US only) authorization (as applicable according to local requirements).
• Currently is receiving at least one antidepressant treatment (i.e., antidepressant drug, maintenance electroconvulsive therapy, or formal psychotherapy including supportive psychotherapy) or mood stabilizing treatment for bipolar patients (such as lithium, anticonvulsants, or atypical antipsychotics).
• Able and willing to comply with the frequency of (outpatient) clinic visits and to reliably complete all the evaluations as specified in the study protocol.Hence based on the nature of their disease, the following patients should not be included: patients with mental retardation, current severe or significant substance/alcohol abuse, diagnosis of one or more schizophrenia-spectrum or other psychotic disorders, diagnosis of borderline or severe personality disorder as determined by clinical judgment which, in the investigator's opinion, would significantly interfere with subject's participation in the study)

Sponsors & Collaborators

• LivaNova: lead

Study Sites (18)

AKH Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

RECRUITING

KU Leuven

Leuven, Belgium

RECRUITING

Sozialstiftung Bamberg - Klinikum am Bruderwald

Bamberg, Germany

WITHDRAWN

Universitätsklinikum Bonn

Bonn, Germany

RECRUITING

Universitätsklinikum Köln

Cologne, Germany

RECRUITING

LVR-Hospital Essen

Essen, 45147, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

COMPLETED

Universitätsmedizin Göttingen

Göttingen, Germany

WITHDRAWN

Medizinische Hochschule Hannover

Hanover, Germany

WITHDRAWN

Universitätsklinikum Jena

Jena, Germany

COMPLETED

Universitätsklinik Leipzig

Leipzig, 04103, Germany

RECRUITING

University Hospital Münster

Münster, Germany

RECRUITING

Klinikum Wilhelmshaven

Wilhelmshaven, Germany

ACTIVE NOT RECRUITING

Glenfield hospital

Leicester, LE3 9EJ, United Kingdom

RECRUITING

King's College London

London, United Kingdom

RECRUITING

Academic Psychiatry Wolfson Research Centre

Newcastle upon Tyne, United Kingdom

RECRUITING

Mendip HTT / St Andrew's Ward

Wells, BA5 1TH, United Kingdom

ACTIVE NOT RECRUITING

Related Publications (4)

• Kavakbasi E, Kraus C, Reif-Leonhard C, Blackwell JM, Dibue M, Treiber M, Achten S, Baune BT. Titration of vagus nerve stimulation for difficult-to-treat depression and onset of response: Early insights from the RESTORE-LIFE study. J Affect Disord. 2025 Jun 1;378:39-46. doi: 10.1016/j.jad.2025.02.047. Epub 2025 Feb 26.

  PMID: 40021060 DERIVED

• Kavakbasi E, Baune BT. Combination of Acute and Maintenance Esketamine Treatment With Adjunctive Long-Term Vagus Nerve Stimulation in Difficult-to-Treat Depression. Neuromodulation. 2024 Jun;27(4):766-773. doi: 10.1016/j.neurom.2023.12.004. Epub 2024 Feb 10.

  PMID: 38340111 DERIVED

• Kavakbasi E, Rosemann K, Yilmaz M, Vasileiadou A, Falcone V, Baune BT. Vagus Nerve Stimulation Combined With Alternating Synchronized and Nonsynchronized Intermittent Theta Burst Stimulation in Difficult-to-Treat Depression. J ECT. 2024 Mar 1;40(1):62-63. doi: 10.1097/YCT.0000000000000964. Epub 2023 Dec 28. No abstract available.

  PMID: 38194603 DERIVED

• Young AH, Juruena MF, De Zwaef R, Demyttenaere K. Vagus nerve stimulation as adjunctive therapy in patients with difficult-to-treat depression (RESTORE-LIFE): study protocol design and rationale of a real-world post-market study. BMC Psychiatry. 2020 Sep 29;20(1):471. doi: 10.1186/s12888-020-02869-6.

  PMID: 32993573 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Koen Demyttenaere, Prof.

  KU Leuven

  PRINCIPAL INVESTIGATOR

• Allan Young, Prof.

  King's College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Funda Basdar

CONTACT

+32 473 97 49 41; funda.basdar@livanova.com

Gaia Giannicola

CONTACT

Gaia.Giannicola@livanova.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 25, 2017
• Study Start: December 14, 2017
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); AU (1); GB (4); DE (12)