Trial document





This trial has been registered retrospectively.
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  DRKS00016537

Trial Description

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Title

REM-sleep disruption and changes in noradrenergic neuronal reaction patterns in patients with sleep disorders or major depression

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Trial Acronym

VNS sleep

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Neurobiological pathways of disturbed sleep and Depression are yet to be fully understood. The proposed study is designed to measure noradrenergic neural transmission in the locus coeruleus via three different potential LC functions, operationalised as REM sleep latency and percentage of total sleep, baseline pupil diameter as a marker of tonic LC activation and P3 amplitude during an auditory oddball paradigm as a marker of phasic LC activation. As hypothesized, an increase in noradrenergic LC function would lead to a decrease in REM parameters, but an improvement in phasic and tonic LC activation.
This study aims to demonstrate whether vagus nerve stimulation modulates these parameters and whether a change in LC function predicts the antidepressant effect. The study targets patients, who are already enrolled for implantation of a stimulation device independently of this study and will consist of two nights of polysomnography, with an auditory oddball task and pupilography in the morning following the second night prior to and 12 months following stimulation onset. In addition, a clinical assessment will be conducted at baseline, 12 months and 18 months following implantation of the stimulation device. Two separate study populations comprising healthy controls and patients with insomnia disorder, but without any other psychiatric condition, will be recruited as control groups.
The results could help to further understand the mechanism of action of vagus nerve stimu-lation and could help refine stimulation parameters in the longterm.

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Brief Summary in Scientific Language

Chronic invasive stimulation of the vagus nerve is established as an effective treatment method for patients suffering from treatment resistant depression. While there are several hints on a high importance of noradrenergic neural transmission in the locus coeruleus, mechanisms of action underlying vagus nerve stimulation remain unclear. The proposed study is designed to measure noradrenergic neural transmission in the locus coeruleus via three different potential LC functions, operationalised as REM sleep latency and percentage of total sleep, baseline pupil diameter as a marker of tonic LC activation and P3 amplitude during an auditory oddball paradigm as a marker of phasic LC activation. As hypothesized, an increase in noradrenergic LC function would lead to a decrease in REM parameters, but an improvement in phasic and tonic LC activation. This study aims to demonstrate whether vagus nerve stimulation modulates these parameters and whether a change in LC function predicts the antidepressant effect. The study targets mostly patients, who are already en-rolled for implantation of a stimulation device independently of this study and will consist of two nights of polysomnography, with an auditory oddball task and pupilography in the morning following the second night prior to and 12 months following stimulation onset. In addition, a clinical assessment will be conducted at baseline, 12 months and 18 months following implantation of the stimulation device. Two separate study populations comprising healthy controls and patients with insomnia disorder, but without any other psychiatric condition, will be recruited as control groups.
The results could help to further understand the mechanism of action of vagus nerve stimulation and could help refine stimulation parameters in the longterm.

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Organizational Data

  •   DRKS00016537
  •   2019/01/14
  •   [---]*
  •   yes
  •   Approved
  •   125/18, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

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Health Condition or Problem studied

  •   F33.2 -  Recurrent depressive disorder, current episode severe without psychotic symptoms
  •   F51.0 -  Nonorganic insomnia
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Interventions/Observational Groups

  •   In MDD patients prior to and following implantation of vagal nerve stimulation LC function will be assessed using REM sleep parameters, pupillometry and reaction to acustically evoked potentials as indirect markers. The examinations take place in an inpatient sleep laboratory for two consecutive nights each. Implantation of VNS will be conducted independent of this study.
  •   In ID patients, LC function will be assessed using REM sleep parameters, pupillometry and reaction to acustically evoked potentials as indirect markers. The examinations take place in an inpatient sleep laboratory for two consecutive nights.
  •   In healthy controls, LC function will be assessed using REM sleep parameters, pupillometry and reaction to acustically evoked potentials as indirect markers. The examinations take place in an inpatient sleep laboratory for two consecutive nights.
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

a) REML, REM (min), REM (%), REMD, EOGS, REM cycles
b) P3 amplitude, baseline pupil diameter
c) Change in BDI/HAMD/MADRAS baseline/12/18 months

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Secondary Outcome

a) NREM sleep parameters
b) Spectral EEG sleep parameters
c) Wake spectral EEG parameters
d) Stimulation intensities
e) Subjective assessments of sleep and depression
f) Comparison to healthy controls and patients with insomnia disorder

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/10/08
  •   45
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

•Ability to provide written informed consent
•Patients with MDD, eligible for and scheduled for treatment with VNS or Patients with ID or healthy controls

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Exclusion Criteria

•Acute suicidal ideations
•Ongoing substance abuse
•For controls: current relevant psychiatric (for ID patients other than ID) or somatic disorder or recurring psychiatric disorder in the past
•Somatic medication potentially confounding outcome variable besides stable psychiatric medication in patients with MDD

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Dr.  Lukas  Frase 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Dr.  Lukas  Frase 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Dr.  Lukas  Frase 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Dr.  Lukas  Frase 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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    • Wissenschaftliche Gesellschaft FreiburgHaus "Zur Lieben Hand"
    • Löwenstr. 16
    • 79098  Freiburg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.