Clinical trial NCT01679145: Learning and Relapse Risk in Alcohol Dependence
Official title: Learning Mechanisms as Predictors of Treatment Outcome in Alcohol- Dependent Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alcohol Use Disorders
Keywords: Reward- based learning
Pavlovian-to-instrumental transfer
Functional imaging
Relapse risk
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
name: University Hospital Carl Gustav Carus
First posted: 2012-09-05
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Detoxified alcohol- dependent patients and age- and gender matched healthy controls living in Germany

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.

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.

Eligibility 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

Primary outcomes:
measure: blood oxygenation level dependent (BOLD) response
timeFrame: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
Secondary outcomes:
measure: Treatment response
timeFrame: 12-month follow-up period beginning after first assessment timepoint
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Technische Universität Dresden
state: Saxony
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus at the Technische Universitaet Dresden
state: Saxony
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Andreas Heinz, Prof MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Carl Gustav Carus, Dresden, Germany
name: Ulrich S Zimmermann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité University, Berlin, Germany
name: Andreas Heinz, Prof MD
role: STUDY_CHAIR
affiliation: Technische Universität Dresden, Dresden, Germany
name: Hans-Ulrich Wittchen, Prof PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Schad DJ, Garbusow M, Friedel E, Sommer C, Sebold M, Hagele 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.