Effects of Vagus Nerve Stimulation (VNS) as a Treatment of Persistent Depression With Comorbid Personality Disorders (Impulse-VNS

Study Overview
=================
Brief Summary
-----------------
In this monocentre two-armed double blind randomised placebo-controlled study - in which the control group obtains the VNS therapy within a defined space of time after 12 weeks - the impact of vagus nerve stimulation on depressive symptomatology of patients with therapy-resistant depressive personality disorders shall be analysed. Particularly in comorbid disorders, medicamentous treatment shows exceedingly bad response rates. Against the background of hitherto insufficient treatment strategies for chronic or persistent depression with comorbidities, the proceeding of a study on the effects of VNS on depressive patients with comorbid disorders is absolutely essential.

Conditions
-----------------
Depression, Comorbid Personality Disorders

Intervention / Treatment
-----------------
* Device: VNS Pulse Model 102
* Device: VNS Pulse Model 102


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria embedding criteria according to VNS manual for doctors diagnosis of a recurrent depressive disorder (based on ICD-10 criteria) and a comorbid personality disorder (according to SKID I/II) with an ailment period of more than six months age 18-80 years verbal IQ (WST) 85 points HAM-D sum score > 20 points at least four depressive episodes in the anamnesis no amelioration of current depressive episodes under two different antidepressants in appropriate dosage for six weeks constant medication within the last two weeks (at the discretion of the supervising doctor) written consent after informing the patient about the study no VNS treatment to date no misuse of illegal drugs or alcohol Women in childbearing age are not permitted to participate in the study if a doctor has asserted the non-existence of pregnancy before the beginning of the study. Furthermore, the procedure of a pregnancy test is recommended after the completion of the study. During the study, a reliable type of contraception (such as the Pill) should be taken. The doctor provides further information. Exclusion criteria according to VNS manual for the doctor present hospitalisation according to the federal states' PsychKG clinically relevant unstable bodily concomitant diseases former VNS treatment reduction of intelligence with verbal IQ < 85 (WST) conceivable use of an MRT examination after the implantation of the VNS-system for diagnostic examinations with the dTMS and the MRT: electric devices (such as cardiac pacemakers, medicine pumps etc.) or pieces of metal (ferromagnetic, e.g. screws after bone fractures) within or at the body, or large-scale tattoos conditions that do not allow to use VNS, such as relevant dysfunctions of the heart's stimulus conduction system or cardiac arrhythmia, stomach ulcer, dysphagia, palsy of parts of the n-vagus nerve insufficient knowledge of the German language pregnancy or lactation current misuse of substances

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Arm I<br>In this branch of study, study participants obtain the VNS therapy after a defined space of time of 12 weeks. | Device: VNS Pulse Model 102<br>* Within this branch, study participants obtain the VNS therapy after a defined space of time of 12 weeks.<br>|
| Experimental: Arm II<br>Within this space of time, study participants obtain the VNS therapy at once. | Device: VNS Pulse Model 102<br>* Individual dosage within the realm of 0,25 mA - 3,5 mA. Uninterrupted stimulation of 24 h.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To analyse whether VNS is effective within the therapy of depression with comorbid personality disorders | The primary objective of this study is to analyse whether VNS is effective within the therapy of depression with comorbid personality disorders. It shall be verified, as a primary hypothesis, whether VNS with ongoing stimulation is significantly predominant to a non-stimulating control with respect to reducing depressive symptomatology (for differences within HAM-D score and the response rate as the percentage of patients with a reduction in the HAM-D score of at least 50%, week 1 - week 12, see flow-chart). | 6 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acquisition of Alteration by means of BDI, TMT-A and B, WMS R, VLMT; WHO-QoL, GAF, CGM, SDS | Acquisition of the improvement of self-rated depressiveness (BDI), stress axis (cortisol of neurocognition, quality of life (WHO-QoL) and impairment through disease (GAF, CGI, SDS), examination of brain structural and functional parametres as predictors for therapy response (VBM-MRT), Region of Interest Approach and proton magnetic resonance spectroscopy, diagnostic TMS (dTMS) in the beginning of the study. | 6 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VNS, Depression, Personality-Disorder, Stimulation