Trial document




drksid header

  DRKS00009944

Trial Description

start of 1:1-Block title

Title

Assessment of non-invasive vagal nerve Stimulation (VNS)-induced head pain-effects in refractory migraine patients: a multimodal fMRI study

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

nVNS fMRT refractory migraine

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Structural , local activity and connectivity MRI measurement before and after 8 weeks of cervical non-invasive vagal nerve stimulation (nVNS) in 40 migraine patients compared to healthy individuals with concomitant pain assessment (intensity and frequency of headaches,medication assessment) and evaluation of migraine-related co-morbidities such as sleep disturbance and depressive symptoms.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Evaluation of nVNS-induced structural, acitvity and morphometric changes in pain processing brain structures related to migraine pathogenesis.
Assessment of structural (VBM), local activity (pCASL) and connectivity (DTI) MRI changes in the „Intrinsic Connectivity Network“ (Default Mode Network, DMN; Salience Network, SN; Central Executive Network, CEN) in chronic and episodic migraine treated with non-invasive vagal nerve stimulation (nVNS) (combined resting state, DTI, VBM MR study).
40 migraine patients will be enrolled and randomized to verum versus sham VNS Treatment for 8 weeks. Migraine-associated co-morbidities and funtional outcome will be measured using MIDAS, BDI and PSQI. In Addition intensitiy and frequency of headache will be recorded.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00009944
  •   2016/02/08
  •   [---]*
  •   yes
  •   Approved
  •   259/15, Ethik-Kommission der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Migraine
  •   R51 -  Headache
  •   G43 -  Migraine
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Arm 1
    Cervical non-invasive vagal nerve Stimulation nVNS
    In the project proposed here, the effects of (25Hz to 5000Hz Burst) nVNS will be investigated in migraine patients for structural and functional changes in comparison to a placebo stimulation and healthy control group.
    Chronic nVNS (25Hz to 5000Hz Burst) 2 times a day with 120 seconds duration (prevention) and at the beginning of migraine attacks on both sides in each case with cervical 120 seconds (acute treatment) will be performed for 8 weeks
    40 migraine patients will be enrolled and randomized to verum versus sham VNS Treatment for 8 weeks. Migraine-associated co-morbidities and funtional outcome will be measured using MIDAS, BDI and PSQI. In Addition intensitiy and frequency of headache will be recorded.
  •   Arm 2
    Sham non-invasive vagal nerve Stimulation

    Sham Treatment with nVNS (25Hz to 5000Hz Burst) 2 times a day with 120 seconds duration (prevention) and at the beginning of migraine attacks on both sides in each case with cervical 120 seconds (acute treatment) will be performed for 8 weeks
    40 migraine patients will be enrolled and randomized to verum versus sham VNS Treatment for 8 weeks. Migraine-associated co-morbidities and funtional outcome will be measured using MIDAS, BDI and PSQI. In Addition intensitiy and frequency of headache will be recorded.
  •   Arm 3
    Healthy controls

    fMRI-scans at baseline and after 8 weeks
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo, Other
  •   Treatment
  •   Parallel
  •   III
  •   No
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

After performing an MRI baseline examination (rsfMRT, pCASL, VBM, DTI), blood sample collection and clinical head pain assessment, migraineurs will receive either verum chronic nVNS (25Hz to 5000Hz Burst) 2 times a day with 120 seconds duration (prevention) and at the beginning of migraine attacks on both sides in each case with cervical 120 seconds (acute treatment), while the other group receive placebo stimulation (in addition healthy individuals will serve as control group) over an identical time scheme over a period of 8 weeks. After 8 weeks, patients are clinically evaluated (pain assessment, see Appendix), blood samples collected along with a follow-up MRI examination (rsfMRT, pCASL, VBM, DTI) in order to detect possible effects of nVNS on structural and functional parameters in the brain and compared to the effects of a Sham-stimulation and healthy controls.
40 migraine patients will be enrolled and randomized to verum versus sham VNS treatment for 8 weeks (20 verum nVNS+sham nVNS). Migraine-associated co-morbidities and funtional outcome will be measured using MIDAS, BDI and PSQI. In Addition intensitiy and frequency of headache will be recorded. In addition a healthy control group of 20 individuals will receive fMRI scans at baseline and after 8 weeks in order to investigate migraine-specific structural and functional brain structure changes

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Correlation between clinical assessment (through interview and patient's headache diary), fMRI findings and the changes in cytokine plasma levels (ELISA) for pro- and anti-inflammatory Mediators before and after 8 weeks VNS treatment (Adiponectin, Ghrelin, HMGB1, Interleukin-1, Interleukin-6, Interleukin-10, Leptin, TNF).

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2016/04/15
  •   60
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   20   Years
  •   60   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- Male / Female subjects
- Right-handedness
- Oral and written informed consent
- Stable headache medication 4 weeks prior to study entry
- Refractory to drug / behavior therapy / psychiatric therapies

-confirmed diagnosis according to IHCD-3 beta
-Willing to fullfil follow-up investigations

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

- Neurological diseases, current and / or history (including severe craniocerebral trauma.)
- Abuse or dependence of analgesic / psychotropic substances including alcohol (except nicotine) in the history or current
- Severe psychiatric disorders in history and currently, serious physical disorders, especially unstable cardiovascular disorders
- Claustrophobia
- Non-removable ferromagnetic metallic implants, probes, stimulators, prostheses, pacemakers, large tattoos, etc.
- Age <25 or> 60 years
- Neuromodulation treatment in prehistory

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • FE Klinische Funktionelle Neurobildgebung, Experimentelle Radiologie Radiologische Universitätsklinik Bonn
    • Mr.  Prof.Dr.med.  Henning  Boecker 
    • Sigmund-Freud-Str. 25
    • 53105 Bonn  Bonn
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Funktionelle Neurochirurgie, Stereotaxie und Neuromodulation, Klinik für Neurochirurgie
    • Mr.  Dr.med.  Thomas M.  Kinfe 
    • Sigmund-Freud-Str. 25
    • 53127  Bonn
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Funktionelle Neurochirurgie, Stereotaxie und Neuromodulation, Klinik für Neurochirurgie
    • Mr.  Dr.med  Thomas M.  Kinfe 
    • Sigmund-Freud-Str. 25
    • 53127  Bonn
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • FE Klinische Funktionelle Neurobildgebung, Experimentelle Radiologie Radiologische Universitätsklinik Bonn
    • Mr.  Prof.Dr.med.  Henning  Boecker 
    • Sigmund-Freud-Str. 25
    • 53105 Bonn  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
  • start of 1:1-Block address otherSupport
    • Funktionelle Neurochirurgie, Stereotaxie und Neuromodulation, Klinik für Neurochirurgie
    • Mr.  Dr.med.  Thomas M.  Kinfe 
    • Sigmund-Freud-Str. 25
    • 53127  Bonn
    • Germany
    end of 1:1-Block address otherSupport
    start of 1:1-Block address contact otherSupport
    end of 1:1-Block address contact otherSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up complete
  •   2018/01/21
end of 1:1-Block state
* This entry means the parameter is not applicable or has not been set.