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

This study is currently recruiting participants.
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
  Purpose

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.


Condition
Alcohol Dependence

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Endophenotyping With fMRI: Genetic Modulation and Treatment Response

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Biospecimen Retention:   Samples With DNA

whole blood (EDTA)


Estimated Enrollment: 480
Study Start Date: June 2008
Estimated Study Completion Date: June 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

primary care clinic

Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01503931

Contacts
Contact: Andreas Heinz, MD 004930450517001 andreas.heinz@charite.de
Contact: Katrin Charlet, MS 004930450517183 katrin.charlet@charite.de

Locations
Germany
Dept. of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Andreas Heinz, MD    004930450517001    andreas.heinz@charite.de   
Sponsors and Collaborators
Charite University, Berlin, Germany
Central Institute of Mental Health, Mannheim
University Hospital, Bonn
Investigators
Principal Investigator: Andreas Heinz, MD Charite University, Berlin, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Andreas Heinz, Prof. Dr. med., Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01503931     History of Changes
Other Study ID Numbers: 01GS08159
Study First Received: January 2, 2012
Last Updated: February 12, 2013
Health Authority: Germany: Federal Ministry of Education and Research

Keywords provided by Charite University, Berlin, Germany:
alcohol dependence, functional magnetic resonance imaging, genetics, endophenotypes, dopamine,
glutamate

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 21, 2014