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Clinical Trials/NCT05875194
NCT05875194UnknownNot Applicable

Investigation of the Influence of Transcranial Direct Current Stimulation (tDCS) on the Brain Activation Measured by fNIRS During the Decision Not to Smoke in High-risk Situations

University Hospital Tuebingen1 site in 1 country60 target enrollmentStarted: October 15, 2022Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Not Applicable
Enrollment
60
Locations
1
Primary Endpoint
Functional connectivity of dlPFC and OFC (fNIRS data)

Study Overview

Brief Summary

Substance use disorders (SUD) are characterized by increased automatized responses to drug-related cues (cue-reactivity) and deficient cognitive control. Cue-reactivity (CR) can be elicited by internal (e.g. mood) or external (e.g. situations) cues closely related to consumption. Therefore, one aim for relapse prevention is to control CR by the enhancement of cognitive control, e.g., via noninvasive brain stimulation (NIBS) of cortical areas involved in inhibitory control. However, thus far, treatment effects of NIBS for relapse prevention in SUD are only moderate, despite clear neurophysiological targets. Critically, NIBS is commonly applied in highly standardized laboratory situation, not related to CR, neglecting the current individual (brain-) state. In the current study, relapse-relevant (brain-) states will be evoked in individual, naturalistic settings outside the laboratory and monitored by functional near-infrared spectroscopy (fNIRS; assessing cortical activation patterns) and heartrate variability (HRV; as a periphery physiological measure) to capture the optimal (cortical) state for subsequent NIBS by means of transcranial direct current stimulation (tDCS). The aim of this highly innovative approach is increasing the efficiency of relapse prevention in SUD. At its heart, multimodal measurements during real-world (substance-related) choices with high ecological validity will be used to identify markers for individual optimal target states for tDCS. In contrast to current approaches, the target brain state of the individual adaptively controls the tDCS to maximize therapeutic outcome. One obstacle is to clear the data from artefacts to interpret data at a single-trial level, which requires this proof-of-concept study. This data is prerequisite for further clinical randomized-controlled studies in patients with SUD.

Detailed Description

Dependent smokers will be measured in the morning, adjusted to the usual time of getting up or a minimum 4-hour abstinence period. All participants will be measured on two days:

Day 1: First, after written consent to participate in the study, all inclusion and exclusion criteria are checked and standardized questionnaires are collected. To validate the activity in the dorsolateral prefrontal cortex (dlPFC) and in the orbitofrontal cortex (OFC) individually, two "localizer measurements" are performed. For the dlPFC, a go/nogo task will be used with smoke-associated and positive images; for the OFC, the same images from the dlPFC localizer will be used and viewed in a "passive viewing task" that will be pushed away by keypress.

Next, a modified version of a cue exposure follows for 5 min that has already been implemented in preliminary studies (Kroczek et al., 2016, 2017). All smokers have their own cigarettes, a lighter, and an ashtray on a table in front of them. The cue-exposure is done twice, once in a laboratory room and once in a naturalistic smoking setting. This condition is used as training for the Support Vector Machine (SVM).

This is followed by a cue exposure in which smokers are allowed to actually decide whether to smoke a cigarette or to resist. This condition occurs only outside, after the first part of the experiment has taken place. In this "50% condition", participants receive the instruction that they are allowed to take a drag on their cigarette after each prompt and they should take a drag in about half of the trials. Smoking behavior (puff on the cigarette/no puff on the cigarette) and also craving is noted by the experimenter.The goal of the first day is to train the SVM to detect maximum cue-reactivity concurrent to its cognitive control by response inhibition

Day 2: At most one week after time point 1, the SVM will be used to promote the cortical activity state that enables effective cue exposure therapy during the exposure condition in the smoking risk situation. With the aid of SVM, a tDCS intervention should be triggered at the optimal moment to further solidify extinction learning. This cue exposure measurement is used to classify successful inhibition of smoking. The measurement will take place in the naturalistic setting outside and the participants are NOT allowed to smoke but should increase their craving. As soon as the desired activity state is reached, indicated by the SVM, but at the latest after 5 minutes, tDCS is applied.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Basic Science
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Masking Description

A person, who is not involved in the study procedure will assign the participants to the sham or treatement condition. The study members will only receive for each stimulation a new number which is necessary to start and encode the type of stimulation (placebo or verum).

Eligibility Criteria

Ages
18 Years to 70 Years (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •informed consent
  • •daily cigarette consumption (already in the first half of the day)

Exclusion Criteria

  • •Acute or chronic disease (also anamnestic) that may affect brain metabolism:
  • •pre-existing diabetes mellitus (E10-E14) according to ICD-10
  • •Renal insufficiency from stage 3 of the Kidney Disease Outcomes Quality Initiative onwards
  • •Uncontrolled hypertension (I10.x according to ICD-10)
  • •Moderate or severe traumatic brain injury (GCS 3-12) or 2nd- or 3rd-degree traumatic brain injury with loss of consciousness > 30 min
  • •Epilepsy (personal or in first-degree relatives).
  • •Currently present psychiatric or neurological disease
  • •Regular use of medications that affect blood flow (e.g., ASA).

Arms & Interventions

active transcranial direct current stimulation (tDCS)

Experimental

A single application of transcranial direct current stimulation (tDCS), anodal stimulation of the left dlPFC placed (10-20 position F3) and the reference electrode on the arm, intensity 2mA, with retangular electrodes, size 35cm2, current intensity is ramped up to 2mA over a period of 20 seconds, duration 15 minutes

Intervention: active transcranial direct current stimulation (tDCS) (Device)

sham transcranial direct current stimulation (tDCS)

Sham Comparator

A single application of transcranial direct sham stimulation (tDCS), with sponge electrodes, placed over left dlPFC (10-20 position F3) and the reference electrode on the arm, with retangular electrodes 35cm2,intensity is ramped up to 2mA over a period of 20 seconds duration and then switched off again at the end of 20 s ramp. To ensure that there are no differences in perception, this is applied in both verum and sham stimulation, duration 15 min

Intervention: active transcranial direct current stimulation (tDCS) (Device)

Outcomes

Primary Outcomes

Functional connectivity of dlPFC and OFC (fNIRS data)

Time Frame: Measurement day 1

cross-correlation between dlPFC and OFC time series

Craving ratings

Time Frame: Measurement day 1

verbally rated, scale from 0-100

Prefrontal fNIRS activity

Time Frame: Measurement day 1

Concentration changes of oxygenated (O2Hb) and deoxygenated (Hhb) hemoglobin in prefrontal regions of interest (dlPFC, OFC)

Activity of the sympathetic nervous system (SNS)

Time Frame: Measurement day 1

Galvanic skin response (GSR) regarding total peaks, amplitudes of peak (microsiemens) and frequency power of GSR as measures

Activity of the parasympathetic nervous system (PNS): Heart-rate variability (HRV)

Time Frame: Measurement day 1

Heart-rate Variabilty (HRV) indexes related to the PNS: RMSSD, pNN50 (in %), HF (in ms2).

Efficacy of extinction learning

Time Frame: 14 days after measurement day 2

Assessment of the amount of self-reported smoked cigarettes and subjective craving (0-100) in a 2-week follow-up period (EMA)

Multimodal SVM craving classifiers

Time Frame: Measurement day 1

The 5-dimensional training vectors (consisting of OFC activity, dlPFC activity, OFC-dlPFC connectivity, GSR, HRV) will be manually assigned a value between -1 and 1 based on the subjective craving ratings. The prediction of the SVM classifier will be tested in the 50:50 condition and related to smoking probability.

Secondary Outcomes

  • Relationship between trait impulsivity scores and number of smoked cigarettes(14 days)
  • Relationship between trait impulsivity scores and subjective craving(Measurement day 1)
  • Relationship between personality traits and state effects (self-efficacy, control beliefs) and craving(Measurement day 1)
  • Relationship between anxiety and general preoccupation and number of smoked cigarettes(14 days)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (1)

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