Trial document





This trial has been registered retrospectively.
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  DRKS00003341

Trial Description

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Title

Endophenotyping with fMRI: Genetic modulation and treatment response

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Trial Acronym

NGFN PLUS TP13

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URL of the Trial

http://www.ngfn.de/en/tp13_endoph__notypisierung_alkoholabh__ngiger_patienten_mit_fmrt__genetische_modulation_und_behandlungsresponse.html

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Brief Summary in Lay Language

Alcohol addiction is one of the most common neuropsychiatric diseases in today’s society. Chronic misuse of alcohol not only causes significant physical and psychological damage in afflicted individuals, it also represents a serious social and economic problem. Despite the availability of a range of psychological and medical therapies, the risk of relapse for dependent individuals remains high even after years of abstinence. New, more effective therapies are urgently needed. Approximately 50% of the predisposition to develop an alcohol addiction is genetically inherited. In order to create improved treatment approaches and novel diagnostic tools, an enhanced knowledge of the genetic basis and biology of alcohol addiction is a prerequisite.
The aim of this multi-centre study is to investigate how and which genetic variations increase the risk for developing an alcohol-addiction. To achieve this, scientists in Berlin, Bonn and Mannheim will examine specific brain mechanisms that play important roles in alcohol dependence. Functional Magnetic Resonance Imaging (fMRI), a technique that makes it possible to observe the brain ‘at work’, will be used to reveal brain mechanisms affected by alcohol addiction such as the processing of reward and punishment, behaviour control and memory. It will then be investigated which genes or gene-gene interactions underlie these neuronal mechanisms. This powerful approach has the potential to uncover ‘addiction-pathways’ through which genes affect personality, drinking behaviours and success in staying abstinent via their influences on neuronal mechanisms.
A special emphasis of this project lies upon the so-called ‘reward system’, which processes naturally rewarding stimuli (e.g. food, sex) and which, in alcohol-dependent individuals, changes perceptions and behaviours in such a way that they become progressively more focused on alcohol. Two major neurotransmitters are involved in the workings of the reward system: ‘dopamine’ and more indirectly ‘glutamate’. The project will investigate how dopaminergic and glutamatergic genes influence the neural mechanisms of reward processing, other neural mechanisms, personality, drinking behaviours and therapy success. In the long run, this knowledge might lead to more effective therapies such as the development of new medications.
This large-scale study will be conducted with several hundreds of alcohol-dependent patients and non-dependent individuals over a period of five years.

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Brief Summary in Scientific Language

The mesolimbic dopaminergic reward system is a key structure underlying addictive behaviour in alcohol addiction and is under control of prefrontal glutamatergic neurotransmission. The aim of the present multicenter-study in Berlin, Bonn and Mannheim is to use fMRI in alcohol addiction for endophenotyping in order to study the relevance of genectic variation, in particular in dopaminergic and glutamatergic genes, for addiction. We will use a temporal discounting and a cue reactivity paradigm in alcoholics and healthy controls in order to 1) test the impact of genetic variation on activation of the mesolimbic system in these populations and to 2) to test their predictive effects for treatment outcome in alcoholics. The subproject will thus bridge animal research on genetically determined cue reactivity and human studies in alcoholics. Furthermore, we will link our results to the measurement of glutamate and glutamine with magnetic resonance spectroscopy (MRS) in subproject SP14.

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Organizational Data

  •   DRKS00003341
  •   2011/11/18
  •   [---]*
  •   yes
  •   Approved
  •   EA1/052/09, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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

  •   F10.2 -  Mental and behavioural disorders due to use of alcohol; Dependence syndrome
  •   [---]* -  [---]*
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Interventions/Observational Groups

  •   alcohol-dependent patients (currently abstinent) will be investigated using functional magnetic resonance imaging (fMRI) und genetic analysis
  •   healthy control subjects will be investigated using functional magnetic resonance imaging (fMRI) und genetic analysis (as a control group for the alcohol-dependent patients)
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   [---]*
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Primary Outcome

The aim of the present multicenter study in Berlin, Bonn and Mannheim is to use fMRI in alcohol addiction for endophenotyping in order to study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction.

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Secondary Outcome

test the impact of genetic variation (within important candidate genes for alcohol dependence using genetic analysis) on activation of the mesolimbic system in alcohol-dependent patients and healthy controls (measured with fMRI) and test their predictive effects for treatment outcome in alcoholics (assessed during 6 months follow-up period)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Actual
  •   2009/06/01
  •   480
  •   Multicenter trial
  •   National
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Inclusion Criteria

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

Healthy Controls
- men and women, aged 18 to 75
- legally effective, written informed consent for participation within the study
- right handedness
- no psychiatric disorder according to ICD 10
- no psychotropic substances within the last 7 days

Alcohol-depdent patients
- men and women, aged 18 to 75
- legally effective, written informed consent for participation within the study
- right handedness
- no other psychiatric disorder according to ICD 10
- no psychotropic substances within the last 7 days

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Exclusion Criteria

- physical disorders, which might interfere with the planned examination (z.B. cerebro-organic disorder)
- MR-contraindication (z.B. pace maker, metalic or electronic implants, metal splinters, Operationsklammern)
- anamnestic manifeste psychiatric axis I disorder and/or axis II according to ICD-10 except alcohol dependence for patients
- medication or drug dependence
- medication or drug abuse (randomisized urin testing)
- insufficient knowledge of German language
- claustrophobia
- for women: pregnancy (exclusion via pregnancy test)

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Addresses

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    • Charité Campus Charité Mitte
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Universitätsklinik BonnAbteilung Medizinische Psychologie
    • Mr.  Prof. Dr. Dr.  Henrik  Walter 
    • Sigmund-Freud-Str. 25
    • 53127  Bonn
    • Germany
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    • Klinik für Abhängiges Verhalten und SuchtmedizinZI Mannheim
    • Mr.  Prof. Dr.  Falk  Kiefer 
    • J5
    • 68159  Mannheim
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    • Klinik für Psychiatrie und Psychotherapie CCM Charité - Universitätsmedizin Berlin
    • Mr.  Prof. Dr.  Andreas  Heinz 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie CCM Charité - Universitätsmedizin Berlin
    • Ms.  Dipl. Psych.  Katrin  Charlet 
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Hannoversche Straße 28-30
    • 10115  Berlin
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2013/05/31
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* This entry means the parameter is not applicable or has not been set.