Modification of Pavlovian and Instrumental Learning in Human Addiction

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Recruiting

CT.gov ID

NCT04032587

Collaborator

(none)

Enrollment

Location

Arms

44.9

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Alcohol Use Disorder (Mild vs. Moderate to Heavy)	Behavioral: Modified training version of the Approach / Avoidance Task (AAT, see Wiers et al., 2011) Behavioral: Mindfulness-based interventions (e.g. body scan)	N/A

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Modification of Pavlovian and Instrumental Learning in Human Addiction

Actual Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-treatment seeking subjects with Alcohol Use Disorder AUD; mild vs. moderate to heavy	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). Behavioral: 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.
Active Comparator: Healthy Controls	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). Behavioral: 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.

Arm

Intervention/Treatment

Experimental: Non-treatment seeking subjects with Alcohol Use Disorder

AUD; mild vs. moderate to heavy

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).

Behavioral: 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.

Active Comparator: Healthy Controls

Behavioral: Modified training version of the Approach / Avoidance Task (AAT, see Wiers et al., 2011)

Behavioral: 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.

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and women aged 16-32 years, 33-49 years, and aged 50-65 years
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
Ability to provide fully informed consent and to use self-rating scales
Willingness to use an android phone
Sufficient understanding of the German language

Exclusion Criteria:

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.
Current threshold DSM-5 diagnosis of major depressive disorder, or presence of suicidal intention
History of severe head trauma or other severe central nervous system disorder (e.g., dementia, Parkinson's disease, multiple sclerosis)
Pregnancy or nursing infants
Current use of medications or drugs known to interact with the CNS within at least four half-life post last intake