Learning and Relapse Risk in Alcohol Dependence (LeAD)

• ClinicalTrials.gov Identifier: NCT01679145
• Recruitment Status: Completed
• First Posted: September 5, 2012
• Last Update Posted: July 28, 2016
• Sponsor: Technische Universität Dresden
• Collaborators: Charite University, Berlin, Germany; University Hospital Carl Gustav Carus
• Information provided by (Responsible Party): Technische Universität Dresden

Study Description

Brief Summary:

The aim of this project is to assess which behavioral and neuroimaging alterations associated with reward- based learning predict relapse in alcohol- dependent patients within a follow- up period of 12 months.

The investigators will explore how these alterations interact with clinical and psychosocial factors which can modify the relapse risk. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) will be used to identify neurofunctional abnormalities in neurotransmitter systems. The investigators will also provide data for genetic analysis and modeling.

Patients will be detoxified in an inpatient setting and followed for 12 months using the Time-Line Follow- Back Procedure. Clinical assessments, behavioral paradigms of learning and brain imaging will be carried out within at least 4 half- lives after any psychotropic medication.

The investigators will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning tasks and associate model parameters of learning with alcohol craving, intake and prospective relapse risk.

Condition or disease
Alcohol Use Disorders

Detailed Description:

This project will examine 150 detoxified alcohol-dependent patients and 100 age- and gender matched controls. The main aim of this project is to assess 1) which behavioural and neuroimaging alterations (fMRI) associated with reward-based learning (see Projects 1 & 3) predict relapse within the follow-up period of 6 months, 2) how these interact with clinical and psychosocial factors which can modify the relapse risk, and 3) to provide data for genetic and imaging analyses and modelling. Furthermore, we will explore gender effects on functional imaging parameters of learning. Patients will be detoxified in an inpatient setting and followed for 6 months using the Form 90 and Time-Line Follow-Back Procedure. Clinical assessments, behavioral paradigms of learning, and brain imaging will be carried out within at least 4 half-lives after any psychotropic medication. Subjects will undergo medical management with bimonthly follow-ups and predefined in- and exclusion criteria as described previously. We will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning as described in Projects 1 and 3. We will associate model parameters of learning with alcohol craving, intake and prospective relapse risk. Independent of these central questions, we will also assess comorbidity, psychosocial and neurobiological disease severity markers to control for specificity of findings.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 225 participants
• Observational Model: Case Control
• Time Perspective: Prospective
• Target Follow-Up Duration: 1 Year
• Official Title: Learning Mechanisms as Predictors of Treatment Outcome in Alcohol- Dependent Patients
• Study Start Date: January 2012
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Groups and Cohorts

Group/Cohort
Alcohol- dependent patients; Detoxified alcohol- dependent patients in an inpatient setting
Control group; Age- and gender matched healthy controls

Outcome Measures

Primary Outcome Measures :

1. blood oxygenation level dependent (BOLD) response [ Time Frame: first assessment time point (alc. dependent pat. 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

Secondary Outcome Measures :

1. Treatment response [ Time Frame: 12-month follow-up period beginning after first assessment timepoint ]
   test the predictive effects of learning parameters and related neuronal correlates for treatment outcome (relapse vs abstinence) in alcohol-dependent patients

Biospecimen Retention:   Samples With DNA

liver encymes

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Detoxified alcohol- dependent patients and age- and gender matched healthy controls living in Germany

Criteria

Inclusion Criteria:

• Alcohol dependence according to DSM-IV
• Minimum of 72 hours of abstinence, maximum of 21 days of abstinence
• Minimum of three years of alcohol dependence
• Low severity of withdrawal symptoms
• Ability to provide fully informed consent and to use self- rating scales

Exclusion Criteria:

• Lifetime history of DSM- IV bipolar or psychotic disorder
• Current threshold DSM-IV diagnosis of any following disorders: current major - depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder or obsessive- compulsive disorder
• History of substance dependence other than alcohol or nicotine dependence

Contacts and Locations

Locations

Germany

Technische Universität Dresden

Dresden, Saxony, Germany, 01187

Universitaetsklinikum Carl Gustav Carus at the Technische Universitaet Dresden

Dresden, Saxony, Germany, 01307

Charité - Universitätsmedizin Berlin

Berlin, Germany, 10117

Sponsors and Collaborators

Technische Universität Dresden

Charite University, Berlin, Germany

University Hospital Carl Gustav Carus

Investigators

• Principal Investigator: Andreas Heinz, Prof MD; Charite University, Berlin, Germany
• Principal Investigator: Ulrich S Zimmermann, MD; University Hospital Carl Gustav Carus, Dresden, Germany
• Study Chair: Andreas Heinz, Prof MD; Charité University, Berlin, Germany
• Study Director: Hans-Ulrich Wittchen, Prof PhD; Technische Universität Dresden, Dresden, Germany

More Information

Additional Information:

Official study group website  English study description 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sebold M, Spitta G, Gleich T, Dembler-Stamm T, Butler O, Zacharias K, Aydin S, Garbusow M, Rapp M, Schubert F, Buchert R, Gallinat J, Heinz A. Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence. J Neural Transm (Vienna). 2019 Sep;126(9):1127-1134. doi: 10.1007/s00702-019-01985-2. Epub 2019 Feb 12.

Schad DJ, Garbusow M, Friedel E, Sommer C, Sebold M, Hägele C, Bernhardt N, Nebe S, Kuitunen-Paul S, Liu S, Eichmann U, Beck A, Wittchen HU, Walter H, Sterzer P, Zimmermann US, Smolka MN, Schlagenhauf F, Huys QJM, Heinz A, Rapp MA. Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk. Eur Arch Psychiatry Clin Neurosci. 2019 Apr;269(3):295-308. doi: 10.1007/s00406-017-0860-4. Epub 2018 Jan 8.

• Responsible Party: Technische Universität Dresden
• ClinicalTrials.gov Identifier: NCT01679145
• Other Study ID Numbers: HE2597/141;ZI1119/31;WI709/101
• First Posted: September 5, 2012
• Last Update Posted: July 28, 2016
• Last Verified: July 2016

Keywords provided by Technische Universität Dresden:

Reward- based learning; Pavlovian-to-instrumental transfer; Functional imaging; Relapse risk

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Ethanol; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Physiological Effects of Drugs