Clinical trial NCT06959342: Modification of Inhibitory Control and Craving Through Transcranial Direct Current Stimulation (tDCS) as an Add-On Treatment for Substance Use Disorder
Official title: Modification of Inhibitory Control and Craving Through Transcranial Direct Current Stimulation (tDCS) as an Add-On Treatment for Substance Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder
Substance Use Disorders
Keywords: Transcranial Direct Current Stimulation
tDCS
Inhibition Training
Electroencephalography
EEG
Inhibitory Control
Working Memory
Craving
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
Collaborators: name: Wellcome Leap Inc.
First posted: 2025-05-06
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this project is to investigate the potential of transcranial direct current stimulation (tDCS) to reduce cognitive deficits and substance craving in individuals with substance use disorders (SUD), with a focus on alcohol use disorder (AUD). Patients of any gender between the ages of 18 and 65 are examined who are in our inpatient and day clinic settings for a standard detoxification treatment program. As there are conflicting findings regarding the effective settings for tDCS as an adjunctive treatment in SUD (e.g., effects on inhibitory control seem to be sensitive to current direction), the aim is to examine and compare three different active tDCS conditions, a sham tDCS condition (placebo), inhibition training, and a control group of patients receiving only standard detoxification treatment. The aim is to identify the optimal electrode placement and current direction to positively influence both inhibitory control and craving, leading to improved treatment outcomes such as longer abstinence periods or reduced substance use after relapse.

Detailed description: The aim of this study is to determine the optimal electrode placement and current direction of tDCS as an adjunctive therapy for SUD to improve both inhibitory control and craving, ultimately contributing to better treatment outcomes such as longer abstinence periods and reduced substance use after relapse. To achieve this, the investigators will assess inhibitory control in SUD patients using computerized neuropsychological testing before and after multiple tDCS sessions with different stimulation protocols. In addition, the effects of tDCS on inhibitory control will be investigated by EEG recordings, focusing on the N2 and P3 components.

To ensure that tDCS stimulation occurs at exactly the same location for each stimulation session, tDCS electrodes (25 cm2) are placed at defined locations in the EEG cap (10/20 system) using saline-soaked sponges. The current is ramped up from 0.3 mA to 2 mA at a rate of 0.1 mA per second and remains at 2 mA for the duration of the active stimulation (20 min total; 0.08 mA/cm2). The tDCS sessions last 20 minutes on five consecutive days.

Four active tDCS stimulations, one sham stimulation, two active control groups and one control group without ad-on treatment are investigated. All groups receive a qualified detoxification treatment in the clinic. First, the investigators want to test whether anodal stimulation is indeed hemispherically sensitive in affecting inhibitory control, while craving reduction is independent of it. Since tDCS (with one anodal and one cathodal electrode) has a poor spatial resolution, the investigators also want to test whether tDCS has a more general effect on brain metabolism and thus on task performance. Therefore, the study includes a control group with anodal stimulation over the occipital cortex at the border with the cerebellum. In addition, computerized inhibition training will be performed to investigate the effects of active, high-frequency contact and behavioral training compared to tDCS. Participants will also receive the same protocol with sham tDCS as well as a no-intervention group to avoid confounding by placebo effects and to control whether participation in the study itself constitutes a "treatment".

On the first examination day (T1), psychometric measures are collected, neuropsychological testing is conducted, and EEG recordings are performed during a modified Go/No-Go task. Depending on group allocation, participants receive their first tDCS session, inhibition training, sham stimulation, or no intervention. On intervention days 2-4 (T2-T4), participants continue their assigned interventions. On day 5 (T5), they receive the final intervention along with another EEG measurement during the Go/No-Go task. Follow-up assessments take place via telephone at 4 weeks (T6), 8 weeks (T7), and 24 weeks (T9) to record self-reported relapse and substance use. At 12 weeks (T8), participants return for an in-person assessment, including EEG measurement during the modified Go/No-Go task.

Eligibility criteria: Inclusion Criteria:

* main diagnosis: alcohol use disorder according to DSM-5
* patients of any gender aged 18 to 65
* normal vision or correctable visual impairment.
* sufficient ability to communicate verbally and in writing
* ability to give fully informed consent after reviewing thorough written information

Exclusion Criteria:

* withdrawal of consent
* severe internal, neurological, or psychiatric comorbidities (e.g., lifetime schizophrenia, bipolar disorder, or other severe mental disorders according to ICD-10 and DSM-5, such as severe depression or PTSD within the last 12 months).
* Exclusion criteria for an EEG/tDCS examination (e.g. metal implants in the head, epilepsy, etc.)
* severe withdrawal symptoms (CIWA-R \> 7)
* alcohol intoxication (breath alcohol concentration \> 0 ‰)
* Pharmacotherapy with psychoactive substances within the last 14 days (exceptions: clomethiazole or benzodiazepines used in withdrawal treatment, provided they were discontinued at least 3 days prior; antidepressants or anxiolytics taken at stable doses).
* drug or alcohol use within the last 7 days
* for women: pregnancy
* suicidal tendencies or danger to others

Primary outcomes:
measure: Inhibitory Control (Go/No-Go Task)
timeFrame: intervention day 1 (T1), intervention day 5 (T5), follow-up after 12 weeks (T8)
measure: Inhibitory Control (EEG)
timeFrame: intervention day 1 (T1), intervention day 5 (T5), follow-up after 12 weeks (T8)
measure: Craving
timeFrame: intervention day 1 and 5 (T1, T5), follow-up after 4 weeks (T6), follow-up after 8 weeks (T7), follow-up after 12 weeks (T8), follow-up after 24 weeks (T9)
Secondary outcomes:
measure: Relapse/Alcohol Use
timeFrame: intervention day 1 and 5 (T1, T5), follow-up after 4 weeks (T6), follow-up after 8 weeks (T7), follow-up after 12 weeks (T8), follow-up after 24 weeks (T9)
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
city: Wiesloch
country: Germany
facility: Psychiatrisches Zentrum Nordbaden (Psychiatric Center Nordbaden)
Study officials:
References:
citation: Stock AK, Riegler L, Chmielewski WX, Beste C. Paradox effects of binge drinking on response inhibition processes depending on mental workload. Arch Toxicol. 2016 Jun;90(6):1429-36. doi: 10.1007/s00204-015-1565-y. Epub 2015 Jul 1.
citation: Stein M, Soravia LM, Tschuemperlin RM, Batschelet HM, Jaeger J, Roesner S, Keller A, Gomez Penedo JM, Wiers RW, Moggi F. Alcohol-specific inhibition training in patients with alcohol use disorder: a multi-centre, double-blind randomized clinical trial examining drinking outcome and working mechanisms. Addiction. 2023 Apr;118(4):646-657. doi: 10.1111/add.16104. Epub 2023 Jan 3.