Clinical trial NCT03320304: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Treatment Resistant Depression
Keywords: Difficult to Treat Depression
TRD
VNS Therapy
Vagus Nerve Stimulation
VNS
Lead sponsor: LivaNova
Sponsor class: INDUSTRY
First posted: 2017-10-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: Duration of response
timeFrame: through study completion, an average of 4 years
measure: Change in MADRS
timeFrame: through study completion, an average of 4 years
measure: Cumulative response
timeFrame: through study completion, an average of 4 years
measure: Cumulative remission
timeFrame: through study completion, an average of 4 years
measure: Changes in depression score As measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR).
timeFrame: through study completion, an average of 4 years
measure: Changes in mania score as measured by the Altman Self-Rating Mania Scale (ASRM)*.
timeFrame: through study completion, an average of 4 years
measure: Changes in Quality of Life as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L)
timeFrame: through study completion, an average of 4 years
measure: Changes in patient function as measured by the Work Productivity and Activity Impairment Scale (WPAI)
timeFrame: through study completion, an average of 4 years
measure: 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)
timeFrame: through study completion, an average of 4 years
measure: Changes in suicidality as measured by item #10 of MADRS.
timeFrame: through study completion, an average of 4 years
measure: Changes in suicidality as measured by item #12 of QIDS-SR.
timeFrame: through study completion, an average of 4 years
measure: Changes in adjunctive antidepressant pharmacological treatment
timeFrame: through study completion, an average of 4 years
measure: Changes in adjunctive antidepressant non-pharmacological treatment
timeFrame: through study completion, an average of 4 years
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: through study completion, an average of 4 years
measure: Changes in cognition
timeFrame: through study completion, an average of 4 years
measure: Changes in anxiety as measured by the Generalized Anxiety Disorder Assessment (GAD 7)*.
timeFrame: through study completion, an average of 4 years
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: AKH Allgemeines Krankenhaus der Stadt Wien
city: Leuven
country: Belgium
facility: KU Leuven
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg - Klinikum am Bruderwald
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: LVR-Hospital Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Leipzig
country: Germany
facility: Universitätsklinik Leipzig
city: Münster
country: Germany
facility: University Hospital Münster
city: Wilhelmshaven
country: Germany
facility: Klinikum Wilhelmshaven
city: Leicester
country: United Kingdom
facility: Glenfield hospital
city: London
country: United Kingdom
facility: King's College London
city: Newcastle Upon Tyne
country: United Kingdom
facility: Academic Psychiatry Wolfson Research Centre
city: Wells
country: United Kingdom
facility: Mendip HTT / St Andrew's Ward
Study officials:
affiliation: KU Leuven
name: Koen Demyttenaere, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College
name: Allan Young, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.