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

January 27, 2016 updated by: Andreas Heinz, Charite University, Berlin, Germany

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

480

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Dept. of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

primary care clinic

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
blood oxygenation level dependent (BOLD) response
Time Frame: first assessment timepoint (alc.dep. patients: up to 21 days after detoxification)
investigation of neuronal activation of the mesolimbic system in alcohol-dependent patients and healthy controls using 3 tesla magnetic resonance imaging
first assessment timepoint (alc.dep. patients: up to 21 days after detoxification)
Genetic endophenotypes
Time Frame: second assessment timepoint: 3 days after first assessment time point
study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction
second assessment timepoint: 3 days after first assessment time point

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment response
Time Frame: 6 month follow up period beginning after second assessment timepoint
test the predictive effects of endophenotypes (genetic and imaging factors) for treatment outcome (relapse vs. abstinence) in alcohol-dependent patients
6 month follow up period beginning after second assessment timepoint

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Collaborators

University Hospital, Bonn
Central Institute of Mental Health, Mannheim

Investigators

  • Principal Investigator: Andreas Heinz, MD, Charite University, Berlin, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (ACTUAL)

February 1, 2013

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

January 2, 2012

First Submitted That Met QC Criteria

January 2, 2012

First Posted (ESTIMATE)

January 4, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 27, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01GS08159

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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