Trial document




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  DRKS00003689

Trial Description

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Title

A randomized, controlled, double-blind, two-arm clinical trial to assess safety and efficacy of transcutaneous vagus nerve stimulation (t-VNS®) in patients with drug-resistant epilepsy

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Trial Acronym

cMPsE02

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Invasive vagus nerve stimulation (VNS) is an approved treatment in drug-resistant epilepsy. The development of a medical device to apply transcutaneous vagus nerve stimulation (t-VNS) meets the demand for a non-invasive therapy with low side-effects. During t-VNS electrical pulses are delivered via electrodes which are placed on the skin of the outer ear. In patients suffering from a form of epilepsy, which can only insufficiently or even not at all be treated with pharmaceuticals a large clinical trial proved VNS to be effective in reducing the seizure frequency. Additionally a small case series with the recently developed t-VNS showed a trend towards a reduction of seizure frequency in the same population. Therefore, the large multicenter and controlled clinical study is conducted to investigate efficiency of t-VNS as an improved version of VNS in the treatment of difficult-to-treat epilepsies. The non-invasive device will be handed to the patient by the investigator and after getting a detailed instruction in its handling, the patient will apply it self-dependently for 4 to maximum 5 hours daily. The efficacy of the therapy in reducing seizure frequency will be estimated via patient seizure diaries. The patient will attend 9 clinical visits during the study which is going to last for 5 months for each patient.

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Brief Summary in Scientific Language

Invasive vagus nerve stimulation (VNS) is an approved treatment in drug-resistant epilepsy. The t-VNS® technology, a non-invasive treatment, uses the fact that the auricular branch of the vagus nerve supplies the cymba conchae of the human ear exclusively. A special ear electrode guarantees that electrical impulses from the pulse generator, which is connected by cable, can be accurately delivered transcutaneously. The excitatory projection of the cervical and the auricular
branches of the vagus nerve to the nucleus of the solitary tract has been shown to activate similar subcortical and cortical areas in the brain. The efficacy of VNS in reducing seizure frequency in patients with pharmacoresistant epilepsy has been shown in a large clinical trial. Based on literature review the non-invasive t-VNS has therefore also got the CE mark for the treatment of epilepsy and a first hint for a similar effect in seizure reduction has been given by a small case series. Therefore the large multicenter clinical study is conducted to prove these results in a higher number of patients. The influence of t-VNS on seizure frequency and on quality of life of participating patients are important outcome parameters of the study.

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Organizational Data

  •   DRKS00003689
  •   2012/04/02
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  •   no
  •   Approved
  •   20_12B, Ethik-Kommission der Friedrich-Alexander-Universität Erlangen-Nürnberg
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   G40 -  Epilepsy
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Interventions/Observational Groups

  •   active group: transcutaneous, non-invasive electrical stimulation of the auricular branch of the vagus nerve by using a specific ear
    electrode. A cable connects this ear electrode with the stimulation unit, which has the size of a mobile phone. In the active arm impulses will be
    given in a high frequency for 4 up to a maximum of 5 hours daily and a period of 20 weeks in total.
  •   active control group: Stimulation with the same kind of medical device and at the same site as done in the active group, but with a lower
    impulse ferquency for 4 up to a maximum of 5 hours daily and a period of 20 weeks in total.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver, assessor, data analyst
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

To evaluate the efficacy of add-on therapy with high-level t-VNS® in comparison to add-on therapy with low-level t-VNS® at reducing seizure-frequency per 28 days in patients with drug-resistant epilepsy, as measured by the change in mean seizure-frequency per 28 days from baseline to the last 28 days of the treatment phase

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Secondary Outcome

To evaluate the safety of add-on therapy with high-level t-VNS® in comparison to add-on therapy with low-level t-VNS® in patients with drug-resistant epilepsy, the frequency, severity, nature and duration of adverse events will be assessed, and changes from baseline in physical exam results and vital signs between the two treatment groups will be compared.
To evaluate the change in seizure-frequency per 28 days from baseline to the treatment period within each group.
To determine the percentage of patients in each treatment group who experience a 25% reduction in seizure-frequency (change from baseline to last 28 days of treatment).
To determine the percentage of patients in each treatment group who experience a 50% reduction in seizure-frequency (change from baseline to last 28 days of treatment).
To evaluate changes in seizure severity in each group from baseline to the last 28 days of treatment.
Via QoLiE-31P, to evaluate changes in the impact of epilepsy on the patients’ quality of life from baseline to the last 28 days of treatment.
Exploratory: To gather information on the ability of treatment with high-level t-VNS® to inhibit the full development of impending seizures.
To gather information on the epilepsy-related use of health-care services by patients with drug-resistant epilepsy.
To gather information on school/work time missed due to epilepsy.
To gather cost-effectiveness data/ data on resource utilization.

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Countries of Recruitment

  •   Germany
  •   Austria
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Locations of Recruitment

  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2012/05/23
  •   70
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

To be eligible for inclusion into this study, the patient must fulfill all of the following criteria prior to enrollment:
Males or females ≥ 18 and ≤ 65 years of age.
Must be able to consent to participation by signing the informed consent form.
Has any of a broad range of epilepsy syndromes (e.g. with simple or complex partial or primary or secondary generalized seizures).
Has ≥ 3 seizures per month and not more than 21 days between seizures, both prior to screening (assessed retrospectively) and during the baseline period.
Is on a stable regimen of ≤ 3 antiepileptic drugs (AEDs), has been on this regimen for at least 5 weeks prior to study enrollment, and maintains this regimen throughout the participation in the study.

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Exclusion Criteria

To be eligible for inclusion into this study, the patient must not meet any of the following criteria prior to enrollment
Is participating in another clinical study at the time of this study, or has participated in another study within 30 days prior to signing the informed consent form.
Is pregnant or breast-feeding.
Is a sexually active female of child-bearing potential unless she is using a reliable, medically-approved primary-form of birth control. At the discretion of the investigator, total abstinence from sexual intercourse is acceptable in those cases where the age, career, lifestyle or sexual orientation of the patient ensures the prevention of a pregnancy.
Is an employee of the investigational site directly affiliated with this study and/or their immediate family members, an employee of the sponsor or the clinical research organization.
Is unwilling or unable to adhere to all study requirements, including accurate completion of the patient diary and questionnaires at the required time points and attending all study visits.
Is unable to understand the study plan, its conditions, the therapy goals and expected outcomes.
Has a substance use disorder (DSM-IV).
Has a major psychiatric disorder (Diagnostic and Statistics Manual of Mental Disorders), such as major depressive disorder or schizophrenia.
Has a deteriorating neurological or medical condition, including for example cerebrovascular degeneration or structural damage to basal ganglia.
Has any relevant cardiac disease, asthma, AIDS or HIV-infection or previous or current diagnosis of any form of cancer other than basal cell carcinoma.
Is using more than 3 AEDs at the time of study enrollment or at randomization.
Has a history of non-epileptic seizures.
Has had more than 1 episode of status epilepticus in the 6 months prior to study enrollment.
Has or has had invasive VNS or deep brain stimulation.
Has undergone ablative epilepsy surgery.
Has undergone cervical vagotomy.
Has a skin pathology or disease such as an infection, psoriasis, or eczema in the treatment area.
Has any anatomical pathology or other limitation that would prevent successful placement of the device.
Has an active implantable medical device such as a cardiac pacemaker, defibrillator, neurostimulator, cochlear implant, or active drug administration device.
Has any other serious medical condition that could adversely affect their participation in the study.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • cerbomed GmbH
    • Mr.  Dr.   Andreas  Hartlep 
    • Henkestr. 91
    • 91052  Erlangen
    • Germany
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    • cerbomed gmbH
    • Mr.  Dr.  Andreas  Hartlep 
    • Henkestr. 91
    • 91052  Erlangen
    • Germany
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    • cerbomed
    • Mr.  Dr.   Andreas  Harlep 
    • Henkestrasse 91
    • 91052  Erlangen
    • Germany
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Sources of Monetary or Material Support

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    • cerbomed GmbH
    • Henkestr. 91
    • 91052  Erlangen
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2014/08/26
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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.