Clinical trial NCT04032587: Modification of Pavlovian and Instrumental Learning in Human Addiction
Official title: Modification of Pavlovian and Instrumental Learning in Human Addiction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Alcohol Use Disorder (Mild vs. Moderate to Heavy)
Keywords: approach / avoidance
alcohol use disorder
stress
stress reduction
goal-directed decision-making
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2019-07-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Blood Oxygen Level Dependent especially within the ventral striatum and the amygdala (fMRI)
timeFrame: 2 consecutive days
measure: Rate of Pavlovian-to-instrumental-Transfer (instrumental responding, i.e.number of button presses, in dependence of Pavlovian Stimuli)
timeFrame: 2 consecutive days
measure: Rate of goal-directed decision-making/habitual decision making
timeFrame: 2 consecutive days
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Dept. of Psychiatry, CCM, Charite Universitätsmedizin Berlin
Study officials:
References:
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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.
citation: 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.
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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.
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.
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.
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.
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.
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.