Trial document




drksid header

  DRKS00003314

Trial Description

start of 1:1-Block title

Title

Searching New Physiological Markers for the Prognosis of Memory Decline in Mild Cognitive Impairment and Temporal Lobe Epilepsy

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

Trial Acronym

[---]*

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

Against our scientific background, we found an analogy in one of their most disabling symptoms between the two different clinical groups that form the focus of our research interest: Epilepsies, especially temporal lobe epilepsies (TLE) and degenerative dementia in its earliest stage, mild cognitive impairment (MCI). While it is obvious that memory problems are the main concern of people with MCI, they are also a major predictor of impaired quality of life and social disability in TLE. Moreover, memory impairments are not only a link between MCI and TLE, but may also act as a starting point from which researchers in each field may add innovative aspects to the corresponding research area.
Specifically, the cause of memory disturbance in both conditions is unclear when patients of each clinical group perform normally on standard neuropsychological tests of memory. This is the case in early stages of MCI. However, memory problems may be detectable with physiological tests.
Thus, the overall aims of our study are:
1. To identify eventual analogies in the pattern of memory impairments in TLE and MCI and to better understand the mechanisms of memory problems in both conditions. This objective will be addressed by comparing these groups by several measures.
2. To make a more accurate prognosis of memory decline by use of modern examinations.
In this study, MCI patients will be divided into a subgroup of evidenced memory impairment, as assessed by standardized tests, and in a subgroup of patients with subjective cognitive complaint, but without objectively measurable abnormality. Additionally we include pharmacoresistant TLE-patients. By entering the study, each patient undergoes several neuropsychological tests, and an electroencephalography. On the second appointment an another electroencephalography will be conducted in addition to a a magnetic resonance imaging. The acquired data will be analyzed with modern techniques. The clinical groups will be compared with a sample of healthy controls in order to determine abnormalities. After 1.5 years, a second session of neuropsychological testing will reveal the degree of memory decline.

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

Brief Summary in Scientific Language

Against our scientific background, we found an analogy in one of their most disabling symptoms between the two different clinical groups that form the focus of our research interest: Epilepsies, especially temporal lobe epilepsies (TLE) and degenerative dementia in its earliest stage, mild cognitive impairment (MCI). While it is obvious that memory problems are the main concern of people with MCI, they are also a major predictor of impaired quality of life and social disability in TLE. Moreover, memory impairments are not only a link between MCI and TLE, but may also act as a starting point from which researchers in each field may add innovative aspects to the corresponding research area.
Specifically, the pathogenesis of memory disturbance in both conditions is unclear when patients of each clinical group perform normally on standard neuropsychological tests of memory. This is the case in early stages of MCI. However, correlates of the subjective observation of memory problems would be detectable with neuroimaging and neurophysiology.
Thus, the overall aims of our study are:
• To identify eventual analogies in the pattern of memory impairments in TLE and MCI and to better understand the mechanisms of memory problems in both conditions. This objective will be addressed by comparing these groups by several measures.
• To increase the validity for prognosis of memory decline by implementing multimodal examination on a single subject base.
In this study, MCI patients will be divided into a subgroup of evidenced memory impairment, as assessed by standardized tests, and in a subgroup of patients with subjective cognitive complaint, but without objectively measurable abnormality. Additionally we include pharmacoresistant TLE patients. By entering the study, each patient undergoes several neuropsychological tests on memory performance, document confounding variables, event-related electroencephalography and magnetic resonance imaging. In order to find individual abnormalities, we will use innovative data-processing techniques and single-subject non-parametric statistics. The extracted features of the clinical groups will be compared with those of a sample of healthy controls in order to determine abnormalities. Specifically, we will assess features which were shown to be of diagnostic or predictive value in one of the two assessed disorders (MCI or TLE). After 1.5 years, a second session of neuropsychological testing will reveal the degree of memory decline. To determine which features from neuroimaging and/or neurophysiology perform best for prognosis, being used alone or in some combination, support vector machines will be applied. Moreover, several automatic classifiers will be compared in order to identify the best suited machine-learning algorithm for prognosis of memory decline.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003314
  •   2011/11/14
  •   [---]*
  •   yes
  •   Approved
  •   1429, Amt der Salzburger Landesregierung Ethikkommission für das Bundesland Salzburg
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

  •   F06.7 -  Mild cognitive disorder
  •   temporal lobe epilepsy
  •   G40 -  Epilepsy
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   healthy subjects
    begin:
    EEG,
    neuropsychological diagnostics;

    2 weeks after begin:
    structural & functional MRI,
    EEG;

    18 months after begin:
    neuropsychological diagnostics;
  •   temporal lobe epilepsy - chronic course and resistance to medication

    begin:
    EEG,
    neuropsychological diagnostics;

    2 weeks after begin:
    structural & functional MRI,
    EEG;

    18 months after begin:
    neuropsychological diagnostics;
  •   mild cognitive impairment; amnestic subtype

    begin:
    EEG,
    neuropsychological diagnostics;

    2 weeks after begin:
    structural & functional MRI,
    EEG;

    18 months after begin:
    neuropsychological diagnostics;
  •   subjective memory complaints; performance 1 standard deviation below average

    begin:
    EEG,
    neuropsychological diagnostics;

    2 weeks after begin:
    structural & functional MRI,
    EEG;

    18 months after begin:
    neuropsychological diagnostics;
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Prognosis
  •   Parallel
  •   N/A
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

prognosis of memory decline by markers in EEG and MRI

EEG: begin: Synchronicity, complexity and frequency distribution during encoding of information (word-pair-learing and watching a movie) and during recall of information(word-pair-recall: free recall and recognition)
EEG: 2 weeks after begin: synchronicity, complexity and frequency distribution during recall of information(word-pair-recall: free recall and recognition; questions about the movie)
MRI: 2 weeks after begin: volumetry, shape, cortical thickness of hippocampus, rhinal and entorhinal cortex and global intensity and deformation.

The validity of the prognosis according to these markers will be evaluated according to the neuropsychologically measured decline of memory (difference between begin and 18 months later).

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

Secondary Outcome

Basic research: analogies in the pattern of physiological changes related with memory decline in MCI and TLE

group comparisons according to the markers:
EEG: begin: synchronicity, complexity and frequency distribution during encoding of information (word-pair-learing and watching a movie) and during recall of information(word-pair-recall: free recall and recognition)
EEG: 2 weeks after begin: synchronicity, complexity and frequency distribution during recall of information(word-pair-recall: free recall and recognition; questions about the movie)
MRT: 2 weeks after begin: volumetry, shape, cortical thickness of hippocampus, rhinal and entorhinal cortex and global intensity and deformation.

tecnical aspects of the analysis: Which algorithms perform best for segmenting the relevant brain regions? Which protocol for segmentation yields the most accurate prognosis?

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

Countries of Recruitment

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

Locations of Recruitment

  • [---]*
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2012/01/01
  •   180
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

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

Additional Inclusion Criteria

MCI: We include 20 level 2 patients (subjective cognitive complaints of memory-related nature) and 20 level 3 patients (mild cognitive impairment; amnestic subtype) according to the “global deterioration scale for aging and dementia” (Reisberg et al., 1982). Level 2 patients are included if they have subjective cognitive complaints of memory-related nature, not reaching the diagnostic criteria on neuropsychological scales for MCI but scoring at least 1 standard-deviation below normative data (Gauthier et al., 2006). Level 3 patients are diagnosed with the CERAD-tests according to Petersen et al. (1999). Patients are included if they report duration of the problems for at least 0.5 and maximal 5 years.
TLE : We include 20 patients with chronic, medication resistant, i.e. not controllable seizures, unilateral TLE. Patients are included regardless presence or severeness of memory deficits.
Healthy controls: 20 subjects will participate in the pre-evaluation of the EEG-paradigms. 80 subjects will serve as control-group for the MCI/TLE groups. The control group will be recruited among the non-genetically connate relatives or friends of the patients to ensure similar demographic factors.

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

Exclusion Criteria

MCI: Patients are excluded if aged below 50 or if vascular, metabolic, traumatic, or psychiatric pathologies as well as pharmacological treatment may better explains the impairment. Thus, only patients with probable degenerative aetiology will be considered.
TLE: Patients with progressive lesions or immune-mediated TLE will be excluded.
Healthy controls: Subjects with psychiatric or neurologic diseases will be excluded.

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

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinik für Neurologie der Paracelsus med. Privatuniversität Salzburg
    • Mr.  Prof. Dr. Mag.  Eugen  Trinka 
    • Ignaz-Harrer-Str. 79
    • 5020  Salzburg
    • Austria
    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
    • Universitätsklinik für Neurologie der Paracelsus med. Privatuniversität Salzburg
    • Mr.  Prof. Dr. Mag.  Eugen  Trinka 
    • Ignaz-Harrer-Str. 79
    • 5020  Salzburg
    • Austria
    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
    • Universitätsklinik für Neurologie der Paracelsus med. Privatuniversität Salzburg
    • Ms.  Dr. Mag. BSc.  Yvonne  Höller 
    • Ignaz-Harrer-Str. 79
    • 5020  Salzburg
    • Austria
    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
    • Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
    • Haus der Forschung, Sensengasse 1
    • 1090  Wien
    • Austria
    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
    • Paracelsus Medizinische Privatuniversität
    • Strubergasse 21
    • 5020  Salzburg
    • Austria
    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
  •   2016/10/31
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.