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

Official title

A Global PRospective, Multi-cEnter, ObServational Post-markeT Study tO Assess shoRt, Mid and Long-term Effectiveness and Efficiency of VNS Therapy® as Adjunctive Therapy in reaL-world patIents With diFficult to Treat dEpression.

Overview

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.

Detailed description

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).

A minimum of five hundred (500) patients will be implanted with a VNS Therapy System and up to eighty (80) sites may participate in this study.

Enrollment will take 8 years, based on competitive enrollment. For each subject a baseline visit will occur between 1 and 6 weeks before implant.

Once implanted with the device, subjects will be followed-up for a minimum of 36 months and a maximum of 60 months. The study may stop when the last subject has reached the 36 months follow-up.

Interventions

• Device Vagal Nerve Simulation (VNS) Therapy
  A VNS Therapy System used for vagus nerve stimulation and consisting of an implantable VNS Therapy generator, lead, and external programming system.

Primary outcome measures

• 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. [Time frame: 12 months]

Secondary outcome measures (12)

• Duration of response [Time frame: through study completion, an average of 4 years]
• Change in MADRS [Time frame: through study completion, an average of 4 years]
• Cumulative response [Time frame: through study completion, an average of 4 years]
• Cumulative remission [Time frame: 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). [Time frame: through study completion, an average of 4 years]
• Changes in mania score as measured by the Altman Self-Rating Mania Scale (ASRM)*. [Time frame: through study completion, an average of 4 years]
• Changes in Quality of Life as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) [Time frame: through study completion, an average of 4 years]
• Changes in patient function as measured by the Work Productivity and Activity Impairment Scale (WPAI) [Time frame: through study completion, an average of 4 years]
• Changes in Quality of Life and patient function as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) [Time frame: through study completion, an average of 4 years]
• Changes in suicidality as measured by item #10 of MADRS. [Time frame: through study completion, an average of 4 years]
• Changes in suicidality as measured by item #12 of QIDS-SR. [Time frame: through study completion, an average of 4 years]
• Changes in adjunctive antidepressant pharmacological treatment [Time frame: through study completion, an average of 4 years]

Eligibility criteria

Inclusion criteria

• 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)

Exclusion criteria

There are no exclusion criteria; the investigator should refer to the (local applicable) VNS Therapy Physician's Manual.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 12 centers

• Sozialstiftung Bamberg - Klinikum am Bruderwald — Bamberg
• Universitätsklinikum Bonn — Bonn
• Universitätsklinikum Köln — Cologne
• LVR-Hospital Essen — Essen
• Universitätsklinikum Frankfurt — Frankfurt
• Universitätsklinikum Freiburg — Freiburg im Breisgau
• Universitätsmedizin Göttingen — Göttingen
• Medizinische Hochschule Hannover — Hanover
• … and 4 more centers

United Kingdom · 4 centers

• Glenfield hospital — Leicester
• King's College London — London
• Academic Psychiatry Wolfson Research Centre — Newcastle upon Tyne
• Mendip HTT / St Andrew's Ward — Wells

Austria · 1 center

• AKH Allgemeines Krankenhaus der Stadt Wien — Vienna

Belgium · 1 center

• KU Leuven — Leuven

Publications

• 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
• 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
• 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
• 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

Identifiers

NCT: NCT03320304 · LNN800

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗