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Endophenotyping With Functional Magnetic Resonance Imaging (fMRI) (NGFN PLUS TP13)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Charite University, Berlin, Germany
Sponsor:
Collaborators:
Central Institute of Mental Health, Mannheim
University Hospital, Bonn
Information provided by (Responsible Party):
Andreas Heinz, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01503931
First received: January 2, 2012
Last updated: February 12, 2013
Last verified: February 2013

January 2, 2012
February 12, 2013
June 2008
February 2013   (final data collection date for primary outcome measure)
  • blood oxygenation level dependent (BOLD) response [ Time Frame: first assessment timepoint (alc.dep. patients: up to 21 days after detoxification) ] [ Designated as safety issue: Yes ]
    investigation of neuronal activation of the mesolimbic system in alcohol-dependent patients and healthy controls using 3 tesla magnetic resonance imaging
  • Genetic endophenotypes [ Time Frame: second assessment timepoint: 3 days after first assessment time point ] [ Designated as safety issue: No ]
    study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction
  • BOLD response - blood oxygenation level dependent [ Time Frame: first assessment timepoint (alc.dep. patients: 5 - 21 days after detoxification) ] [ Designated as safety issue: Yes ]
    investigation of neuronal activation of the mesolimbic system in alcohol-dependent patients and healthy controls using 3 tesla magnetic resonance imaging
  • Genetic endophenotypes [ Time Frame: second assessment timepoint: 3 days after first assessment time point ] [ Designated as safety issue: No ]
    study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction
Complete list of historical versions of study NCT01503931 on ClinicalTrials.gov Archive Site
Treatment response [ Time Frame: 6 month follow up period beginning after second assessment timepoint ] [ Designated as safety issue: No ]
test the predictive effects of endophenotypes (genetic and imaging factors) for treatment outcome (relapse vs. abstinence) in alcohol-dependent patients
Treatment response [ Time Frame: 6 month follow up period beginning after second assessment timepoint ] [ Designated as safety issue: No ]
test the predictive effects of endophenotypes (genetic and imaging factors) for treatment outcome (releapse vs. abstinence) in alcohol-dependent patients
Not Provided
Not Provided
 
Endophenotyping With Functional Magnetic Resonance Imaging (fMRI)
Endophenotyping With fMRI: Genetic Modulation and Treatment Response

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 functional magnetic resonance imaging (fMRI) in alcohol addiction for endophenotyping in order to study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction. The investigators 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, the investigators will link these results to the measurement of glutamate and glutamine with magnetic resonance spectroscopy (MRS) in subproject SP14.

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.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

whole blood (EDTA)

Non-Probability Sample

primary care clinic

Alcohol Dependence
Not Provided
  • Alcohol-dependent 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
  • Healthy control subjects
    • 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
Jorde A, Bach P, Witt SH, Becker K, Reinhard I, Vollstädt-Klein S, Kirsch M, Hermann D, Charlet K, Beck A, Wimmer L, Frank J, Treutlein J, Spanagel R, Mann K, Walter H, Heinz A, Rietschel M, Kiefer F. Genetic variation in the atrial natriuretic peptide transcription factor GATA4 modulates amygdala responsiveness in alcohol dependence. Biol Psychiatry. 2014 May 15;75(10):790-7. doi: 10.1016/j.biopsych.2013.10.020. Epub 2013 Nov 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
480
June 2013
February 2013   (final data collection date for primary outcome measure)

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-dependent 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

Exclusion Criteria:

  • physical disorders, which might interfere with the planned examination (e.g. cerebral or organic disorder)
  • MR-contraindication (z.B. pace maker, metalic or electronic implants, metal splinters, operation clips)
  • anamnestic manifest 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 (randomized urin testing)
  • insufficient knowledge of German language
  • claustrophobia
  • for women: pregnancy (exclusion via pregnancy test)
Both
18 Years to 75 Years
Yes
Contact: Andreas Heinz, MD 004930450517001 andreas.heinz@charite.de
Contact: Katrin Charlet, MS 004930450517183 katrin.charlet@charite.de
Germany
 
NCT01503931
01GS08159
Yes
Andreas Heinz, Charite University, Berlin, Germany
Charite University, Berlin, Germany
  • Central Institute of Mental Health, Mannheim
  • University Hospital, Bonn
Principal Investigator: Andreas Heinz, MD Charite University, Berlin, Germany
Charite University, Berlin, Germany
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP