Learning and Relapse Risk in Alcohol Dependence (FP2)

NCT ID: NCT02615977

Last Updated: 2020-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-06-30

Brief Summary

The investigators will examine clinical alterations in learning and automated approach behaviour and their neurobiological correlates in alcohol-dependent patients and healthy social drinkers and assess whether they are affected by a Zooming Joystick Training (ZJT; randomized "verum" versus "placebo" training) which trains subjects to habitually push alcohol pictures away.

The investigators will test whether activations following treatment predict relapse rate (primary outcome measure) and the prospective amount of alcohol intake (secondary outcome measure) within a six-month follow-up period.

Using fMRI, the investigators will use the Pavlovian-to-Instrumental-Transfer (PIT) paradigm established during the first funding period to distinguish the effects of appetitive, aversive, and drug-related Pavlovian cues on automated instrumental approach behaviour and to assess ZJT training effects comparing functional activation before and after ZJT training.

The investigators will also scan subjects during performance of a short standard working memory task. Behaviourally, aspects of impulsivity will be assessed with the Value-Based Decision Making (VBDM) Battery. Scanning will be repeated after ZJT training to assess its effects on the neural correlates of Pavlovian-to-Instrumental transfer (PIT).

Detailed Description

This Project will examine 130 detoxified alcohol-dependent patients and 40 age- and gender matched controls. All subjects will be treated with Zooming Joystick Task (ZJT) training to alter a habitual alcohol cue approach bias. The primary aim of this project is to assess

1. which behavioural and neuroimaging alterations (fMRI) associated with reward-based learning are altered by ZJT treatment and which alterations predict treatment outcome (primary outcome: relapse, secondary outcome: amount of alcohol intake) within the follow-up period of 6 months,

2. how these alterations interact with clinical and psychosocial factors that can modify relapse risk, and

3. to provide data for genetic and imaging analyses and modelling. Furthermore, the investigators will explore gender effects on functional imaging parameters of learning.

Patients will be detoxified in an inpatient setting, receive six sessions of the ZJT in a randomized placebo controlled design and will be followed for six months using the Time-Line Follow-Back Procedure. Clinical assessments, behavioural paradigms of learning, and brain imaging will be carried out within at least four half-lives after any psychotropic medication. Subjects will undergo medical management with biweekly follow-ups and predefined inclusion and exclusion criteria as previously described. Functional imaging paradigms will be applied, assessing

1. Pavlovian-to-instrumental transfer,

2. habitual versus goal directed behaviour and

3. working memory.

The investigators will associate model parameters of learning with functional activation and prospective intake controlling for comorbidity, psychosocial and neurobiological disease severity markers.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Intervention

In the "verum treatment condition", i.e. Zooming Joystick Task, 90% of all alcohol-related pictures appear in the landscape format and hence are trained to be pushed away.

Group Type: EXPERIMENTAL

Zooming Joystick Task

Intervention Type: BEHAVIORAL

Subjects are instructed to use the joystick to pull all pictures (alcoholic and non-alcoholic beverages) towards them that appear in the portrait format, while pictures in a landscape format are pushed away. Half of the pictures are alcohol-related and the other half is not. The assignment of stimuli (alcohol versus neutral) to the picture format (portrait versus landscape) is manipulated (see 'Study Arm' descriptions).

Arousal and valence of the alcohol and non-alcohol pictures is rated as previously described. The investigators will apply six sessions of ZJT training, as this number has been proven sufficient for reducing relapse rates.

Placebo Intervention

In the placebo condition, i.e. Zooming Joystick Task (Placebo), alcohol picture are as often pushed away as pulled towards the subject.

Group Type: PLACEBO_COMPARATOR

Zooming Joystick Task (Placebo)

Intervention Type: BEHAVIORAL

Subjects are instructed to use the joystick to pull all pictures (alcoholic and non-alcoholic beverages) towards them that appear in the portrait format, while pictures in a landscape format are pushed away. Half of the pictures are alcohol-related and the other half is not. The assignment of stimuli (alcohol versus neutral) to the picture format (portrait versus landscape) is manipulated (see 'Study Arm' descriptions).

Arousal and valence of the alcohol and non-alcohol pictures is rated as previously described. The investigators will apply six sessions of ZJT training, as this number has been proven sufficient for reducing relapse rates.

Interventions

Zooming Joystick Task

Subjects are instructed to use the joystick to pull all pictures (alcoholic and non-alcoholic beverages) towards them that appear in the portrait format, while pictures in a landscape format are pushed away. Half of the pictures are alcohol-related and the other half is not. The assignment of stimuli (alcohol versus neutral) to the picture format (portrait versus landscape) is manipulated (see 'Study Arm' descriptions).

Arousal and valence of the alcohol and non-alcohol pictures is rated as previously described. The investigators will apply six sessions of ZJT training, as this number has been proven sufficient for reducing relapse rates.

Intervention Type: BEHAVIORAL

Zooming Joystick Task (Placebo)

Subjects are instructed to use the joystick to pull all pictures (alcoholic and non-alcoholic beverages) towards them that appear in the portrait format, while pictures in a landscape format are pushed away. Half of the pictures are alcohol-related and the other half is not. The assignment of stimuli (alcohol versus neutral) to the picture format (portrait versus landscape) is manipulated (see 'Study Arm' descriptions).

Arousal and valence of the alcohol and non-alcohol pictures is rated as previously described. The investigators will apply six sessions of ZJT training, as this number has been proven sufficient for reducing relapse rates.

Intervention Type: BEHAVIORAL

Other Intervention Names

Alcohol Approach Avoidance Task; Alcohol Approach Avoidance Task (Placebo)

Eligibility Criteria

Inclusion Criteria

• Men and women aged 18-65 years
• alcohol dependence/alcohol use disorder according to ICD-10 and alcohol-use disorder according to DSM-5
• Minimum of 72 hours of abstinence, maximum of 21 days of abstinence
• Minimum of three years with alcohol dependence/alcohol use disorder
• Low severity of withdrawal symptoms
• Ability to provide fully informed consent and to use self-rating scales
• Sufficient understanding of the German language

Exclusion Criteria

• Lifetime history of DSM-IV bipolar, psychotic disorder, or substance dependence other than nicotine dependence. Patients may have had lifetime alcohol dependence/alcohol use disorder diagnoses.
• Current threshold DSM-IV diagnosis of any of the following disorders: current (hypo)manic episode, major depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder, or obsessive compulsive disorder
• History of substance dependence other than alcohol or nicotine dependence
• Current substance use other than nicotine and alcohol as evinced by positive urine test
• History of severe head trauma or other severe central neurological disorder (dementia, Parkinson's disease, multiple sclerosis)
• Pregnancy or nursing infants
• Any alcohol intake within the last 24 hours
• Use of medications or drugs known to interact with the central nervous system within the last 10 days, except detoxification treatment with benzodiazepines or clomethiazole, with testing at least four half-lives post last intake

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: collaborator

University Hospital Carl Gustav Carus

OTHER

Sponsor Role: collaborator

Technische Universität Dresden

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Heinz, Prof PhD MD

Role: STUDY_CHAIR

Charite University, Berlin, Germany

Hans-Ulrich Wittchen, Prof PhD

Role: STUDY_DIRECTOR

Technische Universität Dresden, Dresden, Germany

Locations

Universitaetsklinikum Carl Gustav Carus at the Technische Universitaet Dresden

Dresden, Saxony, Germany

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Technische Universität Dresden

Dresden, , Germany

Countries

Germany

References

Zindler T, Frieling H, Fliedner L, Veer IM, Neyazi A, Awasthi S, Ripke S, Walter H, Friedel E. How alcohol makes the epigenetic clock tick faster and the clock reversing effect of abstinence. Addict Biol. 2022 Sep;27(5):e13198. doi: 10.1111/adb.13198.

Reference Type: DERIVED

PMID: 36001430 (View on PubMed)

Related Links

http://gepris.dfg.de/gepris/projekt/186318919?language=en

English study description

Other Identifiers

HE2597/142;ZI1119/32;WI709/102

Identifier Type: -

Identifier Source: org_study_id