Modification of Pavlovian and Instrumental Learning in Human Addiction

Healthy Clinical Trial

Official title:

Modification of Pavlovian and Instrumental Learning in Human Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04032587
• Other study ID #: TRR265 C02
• Status: Completed
• Phase: N/A
• Start date: October 1, 2019
• Est. completion date: June 30, 2023

Study information

• Verified date: January 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The project aims at investigating modifications of environmental factors (i.e. cues and stress) relevant for learning mechanisms in addictive disorders.

Description:

Project C02 aims at investigating modifications of environmental factors (i.e. cues and stress) relevant for learning mechanisms in addictive disorders. The investigators will examine non-treatment seeking subjects with alcohol use disorder (AUD; mild vs. moderate to heavy), and healthy controls with a focus on the impact of Pavlovian conditioned stimuli (context-related cues) on instrumental behavior (so-called Pavlovian-to-Instrumental transfer (PIT)) and whether the PIT effect can be systematically modified by manipulating the approach/ avoidance propensities of Pavlovian cues (work package (WP) 1). Concerning stress as a major modulator of cue reactivity in addiction, the investigators further plan to assess whether acute, active stress reduction modifies such PIT effects (i.e. decreasing transfer effects) as well as goal-directed vs. habitual behavior (i.e. strengthening goal-directed decisionmaking) (WP2). Lastly, this project aims at contributing to the understanding of the underlying neurobiological correlates of manipulation of approach/ avoidance propensities of Pavlovian cues and acute stress reduction by using functional magnetic resonance imaging (WP3) with a focus on amygdala-striatal activity (PIT) and frontostriatal processes (goaldirected decision-making).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Men and women aged 16-32 years, 33-49 years, and aged 50-65 years

2. Mild, moderate to heavy alcohol-use disorder (AUD) according to DSM-5 criteria (mild:

2-3 AUD criteria; moderate: 4-5 AUD criteria; heavy: 6 or more AUD criteria); not clinically requiring detoxification (as confirmed by an independent board-certified psychiatrist); AUD patients can have mild to moderate cannabis use disorder as well as tobacco use disorder

3. Ability to provide fully informed consent and to use self-rating scales

4. Willingness to use an android phone

5. Sufficient understanding of the German language

Exclusion Criteria:

1. Lifetime history of DSM-5 bipolar disorder, schizophrenia or schizophrenia spectrum disorder, or substance dependence other than alcohol or nicotine or cannabis dependence. Severe alcohol and cannabis use disorder will be excluded.

2. Current threshold DSM-5 diagnosis of major depressive disorder, or presence of suicidal intention

3. History of severe head trauma or other severe central nervous system disorder (e.g., dementia, Parkinson's disease, multiple sclerosis)

4. Pregnancy or nursing infants

5. Current use of medications or drugs known to interact with the CNS within at least four half-life post last intake

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder (Mild vs. Moderate to Heavy)
• Alcoholism
• Healthy

Intervention

Behavioral:
• Modified training version of the Approach / Avoidance Task (AAT, see Wiers et al., 2011)
First, a modified training version of the Approach Avoidance Task, (see Wiers et al. 2011) with arbitrary Pavlovian cues will be developed and the effectiveness of this manipulation will be assessed. In detail, positive as well as negative Pavlovian cues (derived from a Pavlovian-to-Instrumental transfer Task, see Garbusow et al. 2014, Garbusow et al. 2016) will be modified according to their approach/ avoidance propensities by 1) approaching negative stimuli (pulling joystick), 2) approaching positive stimuli (pulling joystick), 3) avoiding negative stimuli (pushing joystick) and 4) avoiding positive stimuli (pushing joystick). Thus, we aim at reversing the PIT effect (pushing positive cues/ pulling negative cues) or enhancing the PIT effect (pulling positive cues/ pushing negative cues).
• Mindfulness-based interventions (e.g. body scan)
Acute stress reduction will be applied in a standardized way using audio files with an anticipated duration of 20-30 minutes.

Locations

Country	Name	City	State
Germany	Dept. of Psychiatry, CCM, Charite Universitätsmedizin Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (10)

Beck A, Pelz P, Lorenz RC, Charlet K, Geisel O, Heinz A, Wustenberg T, Muller CA. Effects of high-dose baclofen on cue reactivity in alcohol dependence: A randomized, placebo-controlled pharmaco-fMRI study. Eur Neuropsychopharmacol. 2018 Nov;28(11):1206-1216. doi: 10.1016/j.euroneuro.2018.08.507. Epub 2018 Sep 11. — View Citation

Beck A, Schlagenhauf F, Wustenberg T, Hein J, Kienast T, Kahnt T, Schmack K, Hagele C, Knutson B, Heinz A, Wrase J. Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biol Psychiatry. 2009 Oct 15;66(8):734-42. doi: 10.1016/j.biopsych.2009.04.035. Epub 2009 Jun 27. — View Citation

Beck A, Wustenberg T, Genauck A, Wrase J, Schlagenhauf F, Smolka MN, Mann K, Heinz A. Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Arch Gen Psychiatry. 2012 Aug;69(8):842-52. doi: 10.1001/archgenpsychiatry.2011.2026. — View Citation

Beylergil SB, Beck A, Deserno L, Lorenz RC, Rapp MA, Schlagenhauf F, Heinz A, Obermayer K. Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence. Neuroimage Clin. 2017 Apr 17;15:80-94. doi: 10.1016/j.nicl.2017.04.010. eCollection 2017. — View Citation

Friedel E, Schlagenhauf F, Beck A, Dolan RJ, Huys QJ, Rapp MA, Heinz A. The effects of life stress and neural learning signals on fluid intelligence. Eur Arch Psychiatry Clin Neurosci. 2015 Feb;265(1):35-43. doi: 10.1007/s00406-014-0519-3. Epub 2014 Aug 21. — View Citation

Genauck A, Quester S, Wustenberg T, Morsen C, Heinz A, Romanczuk-Seiferth N. Reduced loss aversion in pathological gambling and alcohol dependence is associated with differential alterations in amygdala and prefrontal functioning. Sci Rep. 2017 Nov 24;7(1):16306. doi: 10.1038/s41598-017-16433-y. — View Citation

Koehler S, Hasselmann E, Wustenberg T, Heinz A, Romanczuk-Seiferth N. Higher volume of ventral striatum and right prefrontal cortex in pathological gambling. Brain Struct Funct. 2015 Jan;220(1):469-77. doi: 10.1007/s00429-013-0668-6. Epub 2013 Nov 16. — View Citation

Koehler S, Ovadia-Caro S, van der Meer E, Villringer A, Heinz A, Romanczuk-Seiferth N, Margulies DS. Increased functional connectivity between prefrontal cortex and reward system in pathological gambling. PLoS One. 2013 Dec 19;8(12):e84565. doi: 10.1371/journal.pone.0084565. eCollection 2013. Erratum In: PLoS One. 2015;10(7):e0134179. — View Citation

Romanczuk-Seiferth N, Koehler S, Dreesen C, Wustenberg T, Heinz A. Pathological gambling and alcohol dependence: neural disturbances in reward and loss avoidance processing. Addict Biol. 2015 May;20(3):557-69. doi: 10.1111/adb.12144. Epub 2014 Apr 22. — View Citation

Seo S, Mohr J, Beck A, Wustenberg T, Heinz A, Obermayer K. Predicting the future relapse of alcohol-dependent patients from structural and functional brain images. Addict Biol. 2015 Nov;20(6):1042-55. doi: 10.1111/adb.12302. Epub 2015 Oct 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Oxygen Level Dependent especially within the ventral striatum and the amygdala (fMRI)		2 consecutive days
Primary	Rate of Pavlovian-to-instrumental-Transfer (instrumental responding, i.e.number of button presses, in dependence of Pavlovian Stimuli)		2 consecutive days
Primary	Rate of goal-directed decision-making/habitual decision making		2 consecutive days