Modification of Cue Reactivity by Neurofeedback in Human Addiction

The project is geared towards the understanding of how to increase cognitive control over cue reactivity and drug craving.

Study Overview

• Status: Not yet recruiting
• Conditions: Alcohol Use Disorder (AUD)
• Intervention / Treatment: Behavioral: Treatment as usual (TAU) and neurofeedback (NFB); Behavioral: mindfulness-based relapse prevention (MBRP) and NFB; Behavioral: MBT and sham NFB; Behavioral: TAU and sham NFB

Detailed Description

Project C04 aims at assessing the combined effect of two interventions targeting at reducing striatal cue reactivity and increasing cognitive control, namely mindfulness-based intervention and real-time fMRI neurofeedback. Firstly, the investigators will test whether a prior mindfulness-based intervention (WP1) is able to enhance the effect of rtfMRI NFB (WP2) and change the networks involved in regulation of cue reactivity by providing participants with explicit strategies. Secondly, the investigators will investigate whether this combined intervention leads to a better clinical outcome in terms of decreased heavy drinking days and a reduced sum of alcohol consumption three months later.

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Kirsch, Prof. Dr.; Phone Number: 6501 +49-621/1703; Email: peter.kirsch@zi-mannheim.de
• Study Contact Backup: Name: Falk Kiefer, Prof. Dr.; Phone Number: 3501 +49-621/1703; Email: falk.kiefer@zi-mannheim.de

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68159
      • Klinische Psychologie + Klinik für Abhängiges Verhalten und Suchtmedizin, Zentralinstitut für Seelische Gesundheit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• alcohol use disorder according to DSM-5
• ability to provide fully informed consent and to use self-rating scales
• abstinent after detoxification for at least 5 days
• sufficient understanding of the German language

Exclusion Criteria:

• lifetime history of DSM-5 bipolar, psychotic disorder, or substance dependence other than alcohol or nicotine dependence
• current substance use other than nicotine and/or mild to moderate recreational use of cannabis as evidenced by positive urine test
• current threshold DSM-5 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 severe head trauma or other severe central neurological disorders (dementia, Parkinson's disease, multiple sclerosis)
• pregnancy or nursing infants
• use of medications or drugs known to interact with the CNS within the last 10 days, with testing at least four half-lives post last intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NFB + (MBRP); Neurofeedback (NFB) from target region or control region plus Mindfulness-based relapse prevention (for some)	Behavioral: Treatment as usual (TAU) and neurofeedback (NFB); This group will receive Treatment as usual (TAU) and neurofeedback (NFB). During NFB, participants will be asked to regulate the signal from a target brain region during the presentation of alcohol cues. The ventral striatum was chosen as target region.; Behavioral: mindfulness-based relapse prevention (MBRP) and NFB; This group will receive MBRP and neurofeedback (NFB). MBRP consists of 5 extensive sessions of a specific manualized mindfulness-based intervention for alcohol dependent patients which will be carried out by trained psychologists and psychotherapists. During NFB, participants will be asked to regulate the signal from a target brain region during the presentation of alcohol cues. The ventral striatum was chosen as a target region.; Behavioral: MBT and sham NFB; This group will receive MBRP and sham NFB. MBRP consists of 5 extensive sessions of a specific manualized mindfulness-based intervention for alcohol dependent patients which will be carried out by trained psychologists and psychotherapists. Sham NFB means that the signal displayed to the participant is based on activity in a control region, the auditory cortex, which is not involved in cue reactivity.
Active Comparator: TAU and sham NFB; TAU + Neurofeedback (NFB) from control region	Behavioral: TAU and sham NFB; This group will receive TAU and sham NFB. Sham NFB means that the signal displayed to the participant is based on activity in a control region, the auditory cortex, which is not involved in cue reactivity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neural Level: Blood Oxygen Level Dependent Signal within the ventral striatum	Change of the ability to volitionally modulate brain activation to alcohol cues after training in the target area.	3 consecutive days within up to two weeks
Clinical Level: Number of relapses	MBT and NFB will each lead to a reduced number of relapses during three months after treatment in comparison to the combination of TAU and sham NFB. The combined intervention is expected to lead to a larger reduction compared to the other groups. The investigators expect a higher number of days until relapse, a lower number of heavy drinking days and a lower amount of alcohol consumed by the participants during the follow-up period showing similar group differences.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional changes in brain networks	Functional changes in brain networks related to cognitive control during cognitive task performance between baseline and post-neurofeedback fMRI sessions.	up to two weeks
Drinking type	Short question on which kind of drinking type the participant identifies with the most	up to two weeks
Form 90 (Miller, 1996)	Primary dependent measure of alcohol consumption	up to two weeks
Baratt Impulsiveness Scale (BIS-15) (Meule et al., 2011)	Questionnaire assessing personality/behavioral construct of impulsivity. Scores range from 15 to 60. The BIS-15 has a four-point rating scale with a minimum value of 1 (1 = seldom/never) to a maximum of 4 (4 = almost always/always). Lower scores indicate less impulsivity and higher score mean more impulsivity.	up to two weeks
Sensory Inventory (SI): self-assessment of sensory sensitivity for adults and adolescents (Zamoscik et al., 2017)	Questionnaire on self-assessment of sensory sensitivity. Minimum value: 1 representing "never". maximum value: 7 representing "almost always". Higher scores indicate higher sensitivity for sensory influences.	up to two weeks
General depression scale (german: "Allgemeine Depressionsskala") (Radloff, 1977)	Self-assessment of depressive symptoms. minimum: 0 representing "seldom", maximum: 3 representing "mostly". Higher scores indicate stronger depression.	up to two weeks
Positive and Negative Affect Schedule (PANAS) (Watson et al., 1988)	measures mood/emotion. minimum: 1 representing "not at all", maximum: 5 representing "very much". Depending on the item, higher scores represent higher levels of positive affect and lower scores represent lower levels of negative affect.	up to two weeks.
Perceived Stress Scale (PSS) (Cohen et al., 1983)	measures stress. minimum: 1 representing "never". maximum: 5 representing "quite often". Higher scores indicate higher levels of perceived stress.	up to two weeks
Behavioral Inhibition/Approach System (BIS/BAS) (Carver & White, 1994)	assessing individual differences in the sensitivity of the behavioral approach and the behavioral avoidance system.	up to two weeks
Fagerström Test of Nicotine Dependence (Heatherton et al., 1991)	assessing nicotine dependence	up to two weeks
Visual Craving Scale	Visual Analogue Scale for craving	up to two weeks
Vocabulary test	Neuropsychological test	Collected once during the baseline assessment
Dot-probe task with alcohol stimuli	Change in attentional bias to alcohol-related cues.	Collected once during the baseline assessment
Dimensional card sorting task (Zelazo, 2006)	Neuropsychological test	Collected once during the baseline assessment
Cue reactivity task (Vollstädt-Klein et al., 2011)	fMRI task. Change in BOLD during cue reactivity task.	2 timepoints: Before and after 2 weeks of neurofeedback.
Alcohol Abstinence Self-Efficacy Scale (DiClemente et al., 1994)	measure of craving. minimum: 1 representing "not at all", maximum: 5 representing "enormous". Higher scores indicate a high perceived temptation to drink.	2 weeks
Alcohol Urge Questionnaire (Bohn et al., 1995)	measure of craving	2 weeks
Alcohol Dependence Scale (Ackermann et al., 1999)	measure of craving. Range/response options vary depending on the question. Higher scores are predictive of DSM diagnosis of alcohol dependence.	2 weeks
German Inventory of Drinking Situations (DITS-40) (Victorio-Estrada, 1993)	measure of craving. minimum: 0 representing "never", maximum: 3 representing "almost always". Higher scores indicate a higher frequency to drink.	2 weeks
Craving Automated Scale for Alcohol (CASA) (Vollstädt-Klein et al., 2015)	measure of craving. minimum: 0 representing "never", maximum: 5 representing "always". Higher scores indicate automated craving.	2 weeks

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim

Publications and helpful links

General Publications

• Bohn MJ, Krahn DD, Staehler BA. Development and initial validation of a measure of drinking urges in abstinent alcoholics. Alcohol Clin Exp Res. 1995 Jun;19(3):600-6. doi: 10.1111/j.1530-0277.1995.tb01554.x.
• Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995 Feb;19(1):92-9. doi: 10.1111/j.1530-0277.1995.tb01475.x.
• DiClemente CC, Carbonari JP, Montgomery RP, Hughes SO. The Alcohol Abstinence Self-Efficacy scale. J Stud Alcohol. 1994 Mar;55(2):141-8. doi: 10.15288/jsa.1994.55.141.
• Weiss F, Aslan A, Zhang J, Gerchen MF, Kiefer F, Kirsch P. Using mind control to modify cue-reactivity in AUD: the impact of mindfulness-based relapse prevention on real-time fMRI neurofeedback to modify cue-reactivity in alcohol use disorder: a randomized controlled trial. BMC Psychiatry. 2020 Jun 16;20(1):309. doi: 10.1186/s12888-020-02717-7.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: neurofeedback; mindfulness-based intervention; alcohol use disorder; ventral striatum
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: TRR265 C04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to data protection rules, individual data cannot be shared. Cumulated data on the group level can be made available for meta-analyses on request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No