eMedAlcohol: Alcohol Addiction: A Systems-oriented Approach

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT02910193

Collaborator

Central Institute of Mental Health, Mannheim (Other)

159

Enrollment

Location

36.3

Actual Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of the multicenter subproject (SP) 10 of the eMED Alcohol Addiction Consortium - A Systems-Oriented Approach is to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging and genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related MRI-paradigms tagging the same functional brain systems in both samples (e.g. reward system, inhibitory control system, emotion processing, working memory); (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for juvenile harmful alcohol use in adult patients with alcohol addiction, (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using elaborate imaging genetic methods that are already available and successfully used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using complex computational algorithms and mathematical models, in particular advanced machine learning methods, developed in SP 6. The investigator's approach aims in the long to predict and characterize longitudinal outcomes in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism

Detailed Description

The overall research goal of this project is (i) to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging x genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related paradigms tagging the same functional systems in both samples; (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for harmful alcohol use in adolescents in adult patients with alcohol addiction (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using imaging genetic methods that are already available and used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using computational algorithms and mathematical models, in particular advanced machine learning methods, developed in other sub projects (SPs) of the consortium in particular of SP4 and SP6. The investigator's approach will enable the researchers to characterize outcome longitudinal in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.

Study Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

159 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Alcohol Addiction: A Systems-oriented Approach; Functional Validation II: Neuroimaging x Genetics

Actual Study Start Date :

May 17, 2016

Actual Primary Completion Date :

May 27, 2019

Actual Study Completion Date :

May 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
alcohol-dependent patients
first-degree relatives Parents, children, siblings of alcohol-dependent patients
healthy control subjects

Outcome Measures

Primary Outcome Measures

Functional brain imaging assessed using a Siemens Magnetom TimTrio, 3 Tesla [3 year]
The primary outcome measure "Blood Oxygenation Level-Dependent (BOLD) response" will be assessed as a marker of neural activation via functional brain imaging (fMRI) during the processing of emotional, monetary and alcohol-associated cues as well as cognitive demand and at rest. A Siemens Magnetom TimTrio, 3 Tesla will be used.
Structural brain imaging assessed using a Siemens Magnetom TimTrio, 3 Tesla [3 year]
The second primary outcome measure "brain tissue (Grey Matter, White Matter, Cerebrospinal fluid)" will be assessed and quantified via structural brain imaging using magnet resonance tomography as well as defusion-tensor imaging (MRI, DTI). A Siemens Magnetom TimTrio, 3 Tesla will be used.

Secondary Outcome Measures

Assessment of genetic candidate markers and epigenetic markers of alcohol use disorders [3 years]
Secondary outcome measures will be genotype specification of candidate SNPs (e.g. BDNF, GATA4, OPRM1, D2/D1) derived from blood samples and according DNA/RNA array genotyping. Project aim is to conduct Genom-Wide Association Studies (GWAS) to investigate genetic factors that may predispose to or protect against alcohol use disorder. Further epigenetic methylation factors (i.e. homocysteine serum level) will be investigated to differentiate between healthy controls, alcohol-dependent patients and individuals at risk (first grade relatives).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

written informed consent
right handedness
no psychiatric disorders according to the International Classification of Diseases, Version 10 (ICD-10) (in patients: other than nicotine and alcohol dependence)
no use of psychotropic substances during previous 3 months

Exclusion Criteria:

severe illnesses (e.g. neurological diseases)
MR-contraindications (e.g. pacemaker, metal or electronic implants, metal splinters)
no psychiatric axis I-disorders according to the International Classification of Diseases, Version 10 (ICD-10) (in patients: other than nicotine and alcohol dependence)
no use of psychotropic substances during previous 3 months
insufficient language knowledge
claustrophobia
pregnancy in women