Alcohol DependenceNGFN PLUS TP13NCT01503931
Endophenotyping With Functional Magnetic Resonance Imaging (fMRI)
An observational study of Alcohol Dependence, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
The mesolimbic dopaminergic reward system is a key structure underlying addictive behaviour in alcohol addiction and is under control of prefrontal glutamatergic neurotransmission. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Dependence
- How many people
- 480 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2008to Jun 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: primary care clinic
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Dept. of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
About this study
Official title: 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.
Read the 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.
- Conditions
- Alcohol Dependence
- Keywords
- alcohol dependence, functional magnetic resonance imaging, genetics, endophenotypes, dopamine,, glutamate
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
blood oxygenation level dependent (BOLD) response
investigation of neuronal activation of the mesolimbic system in alcohol-dependent patients and healthy controls using 3 tesla magnetic resonance imaging
Measured: first assessment timepoint (alc.dep. patients: up to 21 days after detoxification)
Genetic endophenotypes
study the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes, for addiction
Measured: second assessment timepoint: 3 days after first assessment time point
Secondary outcomes (1)
Treatment response
test the predictive effects of endophenotypes (genetic and imaging factors) for treatment outcome (relapse vs. abstinence) in alcohol-dependent patients
Measured: 6 month follow up period beginning after second assessment timepoint
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2012 (estimated)
- Study startJun 2008
- Primary completionFeb 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol DependenceStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 480 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Central Institute of Mental Health, Mannheim, University Hospital, Bonn
- Responsible party
- Principal investigator, Andreas Heinz, Charite University, Berlin, Germany
- Investigators
- Andreas Heinz, MD, Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01503931
- Sponsor's protocol ID
- 01GS08159
- Acronym
- NGFN PLUS TP13
- Status last verified
- Jan 2016
- First submitted
- 2 Jan 2012
- Last updated
- 28 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jorde A, Bach P, Witt SH, Becker K, Reinhard I, Vollstadt-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.
PubMed 24314346
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endophenotyping With fMRI: Genetic Modulation and Treatment Response
- ClinicalTrials.gov ID
- NCT01503931
- Acronym / sponsor ID
- NGFN PLUS TP13 / 01GS08159
- Conditions
- Alcohol Dependence
- Keywords
- alcohol dependence, functional magnetic resonance imaging, genetics, endophenotypes, dopamine,, glutamate
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 480 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Central Institute of Mental Health, Mannheim, University Hospital, Bonn
- Study start
- Jun 2008
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 4 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- primary care clinic
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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
1 secondary outcome
Treatment response
Time frame: 6 month follow up period beginning after second assessment timepoint
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2016.
- Derived from this study: PubMed 24314346Jorde A, Bach P, Witt SH, Becker K, Reinhard I, Vollstadt-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.
- Homepage of the project (NGFN PLUS TP 13)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Heinz, MD principal investigator
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alcohol Dependence, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
blood oxygenation level dependent (BOLD) response (time frame: first assessment timepoint (alc.dep. patients: up to 21 days after detoxification)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01503931, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2016.