AAT + tDCS to Reduce Cue-induced Craving and Smoking Behavior

Smoking, Cigarette Clinical Trial

Official title:

AAT + tDCS to Reduce Cue-induced Craving and Smoking Behavior

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05426460
• Other study ID #: STUDY21020160
• Secondary ID: 1R21DA053395-01
• Status: Recruiting
• Phase: N/A
• Start date: April 29, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: May 2024
• Source: University of Pittsburgh
• Contact: Cynthia Conklin, PhD
• Phone: 412-586-9840
• Email: conklinca[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Smokers are highly reactive to smoking-related stimuli and report that this cue reactivity (CR) is a major obstacle to quitting. To date, no pharmacologic methods attenuate CR, and attempts to diminish it with traditional cue exposure treatment (CET) have not proven effective. The proposed study will test a highly novel cue-based smoking treatment adjunct combining an Approach/Avoidance Task (AAT) with brain stimulation via tDCS applied to the dorsolateral prefrontal cortex (dlPFC) during personalized multi-cue exposure; the goal of which is to discover an effective means of reducing cue reactivity and daily smoking, and increasing intent and confidence to quit, among high treatment-interest smokers.

Description:

Exposure to smoking-related cues robustly increases self-report craving and immediate subsequent smoking. This cue-reactivity (CR) is an often-reported obstacle to quitting among smokers. Unlike methods to diminish abstinence-induced craving, which have been highly successful with the advent of nicotine replacement therapies (NRTs), pharmacotherapies have not been shown to diminish smoking-related reactivity to cues. Past behavioral methods to reduce smokers' CR, most commonly extinction training through cue-exposure treatment (CET), have also consistently failed. Review of past CET studies reveals that this failure is largely due to several methodological shortcomings including: (1) presenting only proximal cues (e.g., cigarettes, ashtrays), (2) conducting passive unreinforced exposure to these limited cues, and (3) achieving only limited new learning. The researchers extensive past cue work makes them uniquely qualified to remedy these flaws by designing and testing novel CET methodology incorporating contemporary techniques and technology to reduce CR and relieve smokers of this ubiquitous source of relapse risk. The researchers propose three methods to improve CET. First, using well-tested methods for personalizing smoking cues and presenting numerous proximal, environment, and people cues in combination, the proposed cue exposure will better capture and target the cue-rich situations most likely to trigger smokers' strongest CR. Second, rather than repeated passive unreinforced exposure to cues, smokers will engage in active re-training of approach biases toward their personal smoking stimuli using an Approach/Avoidance Task (AAT), a method shown to activate the dorsolateral prefrontal cortex (dlPFC), a brain region associated with both cognitive control over craving and deactivation of drug reward systems. Third, to enhance new learning, smokers will undergo non-invasive transcranial direct current brain stimulation (i.e., tDCS) of the dlPFC. Although the researchers propose each method, AAT and tDCS, should independently reduce smokers' CR to their most salient cues, providing AAT with simultaneous tDCS (AAT+tDCS) should synergistically attenuate CR by better increasing cortical excitability in the dlPFC. To assess this, a 2 x 2 active and sham-controlled test of AAT and tDCS during personalized multi-cue exposures will be used to examine pre-post training changes across several measures of smoking-related cue reactivity (cue-induced craving, cue-provoked smoking topography, and attentional bias measures of Evoked Response Potentials (ERPs) and reaction time), as well as changes in daily smoking and confidence and intent to quit pre-post training and at 1 week and 1-month follow up. The goal of this work is to develop an efficacious treatment adjunct that better prepares smokers to confront cues when they try to remain quit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 26 Years to 55 Years

Eligibility

Inclusion Criteria:

• Between the ages of 26 & 55
• High treatment interest (planning to quit within the next 6 months)
• Ability to provide written informed consent
• Smoke equal or greater than 7 cigarettes per day
• Expired breath carbon monoxide (CO) equal or greater than 8 ppm at screening
• Ability to attend 10 sessions over a 3-week period, and complete 2 follow-up phone assessments

Exclusion Criteria:

• Epilepsy or Current Seizure Disorder
• Alcohol or Substance Dependence past 3 months (caffeine allowed, nicotine is part of inclusion criteria, alcohol > 14 drinks per week (M) or > 7 drinks per week (F))
• Implanted cardiac or brain medical devices
• History of epilepsy or current seizure disorder
• History of brain surgery or skull fracture
• History of a head trauma (losing consciousness >10 min and/or problems with speech or movement because of head injury)
• Latex allergy
• Scalp irritation
• History of diabetes that caused loss of consciousness (>10 min) or weakness in your arms or legs
• History of electroconvulsive therapy (ECT) in the last 5 years (Y / N) History of ECT within the last 5 years
• Current use of dextromethorphan
• Diagnosed with or undergone treatment for alcohol or substance dependence past 3 months
• Uncorrected vision deficit
• Colorblindness
• Use of tobacco products other than commercially available cigarettes

Related Conditions & MeSH terms

• Smoking Behaviors
• Smoking, Cigarette

Intervention

Behavioral:
• Approach/Avoidance Task
The Approach/avoidance task (AAT) training is done using a joystick. The AAT tasks involves having participants push away pictures of smoking stimuli that appear on the screen by pushing the joystick forward, and pulling in pictures of nonsmoking stimuli that appear on the screen by pulling the joystick towards themselves. Pushing smoking-related pictures away causes the picture to shrink in size, whereas pulling a picture closer causes the picture to increase in size. This task consists of 4 blocks of 24 pictures, taking 30 minutes.

Device:
• Transcranial Direct Current Stimulation
Transcranial Direct Current Stimulation active (2.0 mA) (tDCS) will be used to temporarily increase cortical excitability of the dorsolateral prefrontal cortex (dlPFC) in healthy daily smokers. Participants assigned to active tDCS conditions will receive active (2.0 mA) tDCS, with anode electrode placement over the right dlPFC and cathode electrode placement over the left bicep. tDCS will be administered the first 20 minutes of each of the five 30 minute AAT training sessions.

Behavioral:
• AC
During Active Control (AC) participants press a button on the left of right of the joystick to indicate the position the picture on a screen. Position of pictures will be balanced across the 4 blocks of 24 pictures, taking 30 minutes.

Device:
• Sham tDCS
Sham transcranial Direct Current Stimulation (0.1 mA) (sham tDCS) will be used as a control for active tDCS with anode electrode placement over the right dlPFC and cathode electrode placement over the left bicep. Sham tDCS will be administered during the first 20 minutes of each of the four blocks of 24 pictures, taking 30 minutes, across the 5 training sessions.

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Cynthia Conklin	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change from baseline in 4-item Questionnaire on Smoking Urges craving score during cue reactivity to personal cues	Difference between cue-induced craving rating from pre-treatment (Baseline) to post-treatment (re-test)	Baseline to approximately 1 week
Primary	Mean Change from baseline in number cigarettes smoked daily	Difference in mean number of cigarette smoker per day from pre-treatment (Baseline) to post-treatment (re-test)	Baseline to approximately 1 week
Primary	Mean Change from baseline in number cigarettes smoked daily	Difference in mean number of cigarette smoker per day from pre-treatment (Baseline) to 1 week post treatment (follow-up)	Baseline to approximately 2 weeks
Primary	Mean Change from baseline in number cigarettes smoked daily	Difference in mean number of cigarette smoker per day from pre-treatment (Baseline) to 1 month post treatment (follow-up)	Baseline to approximately 6-weeks
Primary	Mean Change from baseline in rating score for 5-item Intent to Quit Questionnaire	Difference between Intent to Quit score from pre-treatment (Baseline) to post treatment (re-test)	Baseline to approximately 1-week
Primary	Mean Change from baseline in rating score for 5-item Intent to Quit Questionnaire	Difference between Intent to Quit rating from pre-treatment (Baseline) to 1 week post-treatment (follow-up)	Baseline to approximately 2-weeks
Primary	Mean Change from baseline in rating score for 5-item Intent to Quit Questionnaire	Difference between Intent to Quit rating from pre-treatment (Baseline) to 1 month post-treatment (follow-up)	Baseline to approximately 6-weeks
Primary	Mean Change from baseline in rating score for Confidence to Quit Questionnaire	Difference between Confidence to Quit score from pre-treatment (Baseline) to post-treatment (re-test)	Baseline to approximately 1-week
Primary	Mean Change from baseline in rating score for Confidence to Quit Questionnaire	Difference between Confidence to Quit score from pre-treatment (Baseline) to 1 week post-treatment (follow-up)	Baseline to approximately 2-weeks
Primary	Mean Change from baseline in rating score for Confidence to Quit Questionnaire	Difference between Confidence to Quit score from pre-treatment (Baseline) to 1 month post-treatment (follow-up)	Baseline to approximately 6-weeks
Secondary	Sex as a moderator of cue-induced craving	The correlation between sex (male / female) and QSU-rating difference score (craving rating to smoking cues minus craving to neutral cues) from pre- to post training.	Baseline to approximately 1 week
Secondary	Sex as a moderator of cigarettes smoked per day	The correlation between sex (male / female) and change in number of cigarettes smoked per day from pre- to post training.	Baseline to approximately 1 week
Secondary	Sex as a moderator of cigarettes smoked per day	The correlation between sex (male / female) and change in number of cigarettes smoked per day from pre-training to 1 week follow-up.	Baseline to approximately 2 weeks
Secondary	Sex as a moderator of cigarettes smoked per day	The correlation between sex (male / female) and change in number of cigarettes smoked per day from pre-training to 1 month follow-up.	Baseline to approximately 6 weeks
Secondary	Age as a moderator of cue-induced craving	The correlation between QSU-rating difference score (craving rating to smoking cues minus craving to neutral cues) from pre- to post training.	Baseline to approximately 1 week
Secondary	Age as a moderator of of cigarettes smoked per day	The correlation between change in number of cigarettes smoked per day from pre- to post-training.	Baseline to approximately 1 week
Secondary	Age as a moderator of of cigarettes smoked per day	The correlation between change in number of cigarettes smoked per day from pre-training to 1 week follow-up.	Baseline to approximately 2 weeks
Secondary	Age as a moderator of of cigarettes smoked per day	The correlation between change in number of cigarettes smoked per day from pre-training to 1 month follow-up.	Baseline to approximately 6 weeks
Secondary	Baseline measure of Fagerstrom Test of Nicotine Dependence (FTND) as moderator of cue-induced craving.	The correlation between Fagerstrom Test of Nicotine Dependence (FTND)and QSU-rating difference score (craving rating to smoking cues minus craving to neutral cues) from pre- to post training.	Baseline to approximately 1 week
Secondary	Baseline measure of Fagerstrom Test of Nicotine Dependence (FTND) as moderator of cigarettes per day	The correlation between Fagerstrom Test of Nicotine Dependence (FTND) as a predictor of change in number of cigarettes smoked per day from pre- to post-training.	Baseline to approximately 1 week
Secondary	Baseline measure of Fagerstrom Test of Nicotine Dependence (FTND) as moderator of cigarettes per day	The correlation between Fagerstrom Test of Nicotine Dependence (FTND) as a predictor of change in number of cigarettes smoked per day from pre-training to 1-week follow-up..	Baseline to approximately 2 weeks
Secondary	Baseline measure of Fagerstrom Test of Nicotine Dependence (FTND) as moderator of cigarettes per day	The correlation between Fagerstrom Test of Nicotine Dependence (FTND) as a predictor of change in number of cigarettes smoked per day from pre-training to 1-month follow-up.	Baseline to approximately 6 weeks