Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00007874

Trial Description

start of 1:1-Block title

Title

Implicit and explicit learning and memory processes in acute hippocampal impairment: The role of stress

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

http://www.sfb636.de/29.html?&L=1

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

Brief Summary in Lay Language

Transient global amnesia (= memory loss), abbreviated TGA, is a sudden and temporary episode of memory loss. During a TGA episode, patients cannot recall recent events and therefore do not understand what is happening around them. Typically, patients do remember well who they are and are able to perform even complex motor tasks. During TGA attacks, the patients repeatedly ask the same questions again and again, but do not remembering the answers they are given. Although the memory disturbance resolves completely after a few hours, a permanent memory gap for this episode itself will remain. Interestingly, many patients and their relatives describe typical precipitating events, typically summarized as "mental and physical stress". We hypothesize, that the disorder is caused by a stress-mediated disturbance of brain areas responsible for memory formation.

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

Brief Summary in Scientific Language

The aim of this project is to investigate the effect of stress and hypothalamus-pituitary-adrenal (HPA) axis function on implicit and explicit learning and memory processes in the state of acute hippocampal impairment in a cohort of patients with transient global amnesia (TGA).

TGA is a neurological disorder characterized by the acute onset of severe anterograde memory loss that usually resolves within 24 hours. In up to 90% of cases, an emotionally or physically charged event precedes the onset of TGA. By using magnetic resonance imaging (MRI) following a TGA episode, we have observed small lesions in the hippocampus and hence hypothesize that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. To test this assumption, we will determine the effect of experimental exposure to stress (socially evaluated cold pressor test, SECPT) on cortisol levels and on hippocampal activation patterns in implicit and explicit memory and learning paradigms by functional MRI in the following cohorts: patients with acute TGA, and healthy control subjects.

We will analyze cortisol levels during and after TGA, in response to the dexamethasone suppression test, as well as under experimental stress conditions. We expect TGA patients to exhibit an altered HPA axis reactivity resulting in increased cortisol values. To show that changes in brain activation patterns during memory formation and retrieval are a pathophysiological correlate of TGA, we will employ fMRI measurements based on two different approaches to assess hippocampal function. In a recognition memory paradigm, we expect only the performance in the recollection aspect (hippocampal memory) to be affected in TGA patients (with a specific reduction in hippocampal activation in contrast to healthy controls), while extra-hippocampal memory processes (familiarity) should remain intact. We will additionally employ a contextual fear conditioning fMRI task that has been shown to lead to significant hippocampal activation. We assume that the activation produced by this paradigm will also be reduced and that extinction processes will be differentially affected in TGA patients as compared to controls. In addition to understanding the pathophysiology of TGA, the results of this study may aid to understand the development
and maintenance of anxiety disorders and depression, in which altered hippocampus-related learning processes play a crucial role.

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

Organizational Data

  •   DRKS00007874
  •   2015/03/11
  •   [---]*
  •   yes
  •   Approved
  •   2011-309N-MA, Medizinische Ethik-Kommission II Medizinische Fakultät Mannheim der Universität Heidelberg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1167-9400 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   G45.4 -  Transient global amnesia
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Patients with a transient global amnesia, still in the acute episode at the time of study recruitment.

    Sequence of examinations:

    T0 (day 0):
    - physical examination
    - short structured neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; DWI; FLAIR)
    - 3 salivary cortisol measurements: in ER, directly before MRI and after MRI

    T1 (day 1):
    - neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; fear conditioning fMRI; DWI; FLAIR; MR-Angio; 3D-MP-RAGE)
    - 2 salivary cortisol measurements: directly before MRI and after MRI
    - after MRI SECPT or control procedure with warm water (randomized order), recording of blood pressure, heart rate and salivary cortisol measurements)

    in between (after discharge):
    - salivary cortisol day profile measurement
    - after intake of dexamethasone at 11 p.m. second salivary cortisol day profile measurement

    T2 (day 10-20):
    - neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; fear conditioning fMRI; DTI)
    - 2 salivary cortisol measurements: directly before MRI and after MRI
    - after MRI control procedure with warm water or SECPT (randomized order), recording of blood pressure, heart rate and salivary cortisol measurements)
  •   Healthy control persons

    Sequence of examinations:

    T0 (day 0):
    - physical examination
    - short structured neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; DWI; FLAIR)
    - 3 salivary cortisol measurements: in ER, directly before MRI and after MRI

    T1 (day 1):
    - neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; fear conditioning fMRI; DWI; FLAIR; MR-Angio; 3D-MP-RAGE)
    - 2 salivary cortisol measurements: directly before MRI and after MRI
    - after MRI SECPT or control procedure with warm water (randomized order), recording of blood pressure, heart rate and salivary cortisol measurements)

    in between:
    - salivary cortisol day profile measurement
    - after intake of dexamethasone at 11 p.m. second salivary cortisol day profile measurement

    T2 (day 10-20):
    - neuropsychological testing
    - stress questionnaires
    - MRI (resting state fMRI; fear conditioning fMRI; DTI)
    - 2 salivary cortisol measurements: directly before MRI and after MRI
    - after MRI control procedure with warm water or SECPT (randomized order), recording of blood pressure, heart rate and salivary cortisol measurements)
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Blinded
  •   assessor, data analyst
  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   No
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Changes in brain networks measured with resting-state fMRI (T0, T1, T2), between the two groups and within the TGA Group (arm 1) over time

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

Secondary Outcome

Group comparison between arm 1 and arm 2 concerning:
- acute cortisol values and cortisol dynamic
- cortisol day profile and dexamethasone suppression test
- stress reactivity (SECPT and control procedure)
- neuropsychological Parameters
- stress scales
- fear conditioning fMRI
- DTI
- hippocampus volumetry
- further clinical, laboratory and MRI Parameters

Descriptive statistics of the TGA group (arm 1):
- Dynamics of the cortisol values in the acute Phase
- neuropsychological characterization in the acute phase
- number and localization of DWI changes

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
  •   2013/08/12
  •   40
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

Arm 1:
- transient global amnesia
- patient is still in the Episode

Arm 2:
- healthy control subject, no acute disease

Both groups:
- right-handed person
- written consent to participate in the study

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

Exclusion Criteria

Arm 1:
- episode of anterograde amnesia has already ended

Both groups:
- contraindication against MRI
- taking cortisol preparations

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

Addresses

  • start of 1:1-Block address primary-sponsor
    • UniversitätsMedizin Mannheim
    • 68167  Mannheim
    • 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 other
    • Institut für Neuropsychologie und Klinische PsychologieZentralinstitut für Seelische Gesundheit
    • Ms.  PD Dr.  Frauke  Nees 
    • J5
    • 68169  Mannheim
    • Germany
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • Neurologische KlinikUniversitätsMedizin MannheimUniversität Heidelberg
    • Ms.  Prof. Dr.  Kristina  Szabo 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • 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
    • Neurologische KlinikUniversitätsMedizin MannheimUniversität Heidelberg
    • Mr.  Dr.  Martin  Griebe 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • 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
    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  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
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
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.