Behavioral Memory Modulation in Nicotine Addiction

Nicotine Use Disorder Clinical Trial

Official title:

Targeting Foundational Memory Processes in Nicotine Addiction: A Translational Clinical Neuroscience Study of a Retrieval-Extinction Intervention to Reduce Craving and Smoking Behavior

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03744559
• Other study ID #: 00069355
• Secondary ID: R01DA043587
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 4, 2019
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to see if a behavioral intervention known as retrieval-extinction training (RET) might affect craving in response to nicotine cues (e.g., pictures, videos and objects) and smoking behavior in men and women who smoke cigarettes.

Description:

In a recently published NIDA-funded study, the investigators found that lasting reductions in craving and smoking could be achieved with a brief behavioral intervention designed to alter memory processes underlying smoking-related nicotine addiction. The proposed project will replicate and extend these findings by 1) increasing the dose of intervention so as to bolster the observed treatment effects, 2) employing brain imaging methods to identify patterns of brain activity uniquely associated with the intervention and potentially predictive of treatment outcome, 3) extending follow-up period to more completely document the long-term effects of the intervention. Positive findings from this study could lead to the development of brief therapy that will not only improve treatment outcomes for smokers, but also be used in the treatment other substance use disorders and frequently co-occurring comorbidities such as PTSD.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 191
• Est. completion date: January 2025
• Est. primary completion date: October 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria

1. Healthy men and women, ages 25 to 65, who have smoked at least 10 cigarettes per day for at least 3 years.

2. Participants must live within a 50-mile radius of the research facility and have reliable transportation.

3. Participants must be willing to abstain from smoking starting the night before the baseline visit, and starting the night before visit 1 and remain abstinent for four consecutive days.

4. Participants must agree to forego any other medication or behavioral treatment for smoking cessation while enrolled in the study (with the exception of the SC Quitline).

Exclusion Criteria

1. Participants who are dependent on substances other than nicotine.

2. Women who are pregnant during the clinical assessment session or either of the fMRI sessions. These participants must agree to notify the study staff if they become pregnant during the study.

Related Conditions & MeSH terms

• Nicotine Use Disorder
• Tobacco Use Disorder

Intervention

Behavioral:
• Retrieval Extinction Training (RET)
Retrieval extinction training (RET) is a behavioral intervention that involves cue-elicited retrieval followed by extinction training (i.e., massed unreinforced exposure to drug-associated cues). The first element of RET involves briefly presenting drug-associated cues to retrieve drug use memories. The second element, occurring after a brief interval, involves extinction training. It is argued that the initial retrieval of the memories prior to extinction training initiates a period of instability, which is followed by reconsolidation of the memories back into long-term storage. Extinction training during the period of instability is presumed to overwrite the original drug-associated cue with a non-drug-associated cue, to attenuate expression of drug-seeking behavior.
• Control Retrieval Extinction Training (RET)
The control retrieval extinction training (RET) for the NR-E arms serves as the control intervention to the RET behavioral intervention. The first element of the control RET involves briefly presenting retrieval cues that contain neutral, non-smoking content. The second element, occurring after a brief interval, involves extinction training. Based on findings from the previous NIDA-funded R21, the R-E arm reported a significant 25 percent reduction in cigarettes smoked per day during the follow-up period versus the control NR-E arm.

Other:
• Functional magnetic resonance imaging (fMRI)
Functional magnetic resonance imaging (fMRI) will identify patterns of brain activity associated with RET and potentially predictive of treatment outcomes. The fMRI is used during the baseline and 24-hour follow-up test sessions while participants complete a cue-reactivity task. The collection of fMRI data is based on findings from human fear conditioning fMRI studies, in which groups receiving RET in the reconsolidation window exhibited less fear that was associated with attenuated BOLD response in the amygdala, relative to the control. We propose that the R-E arm will evidence attenuated cue reactivity in medial prefrontal cortex, limbic regions and ventral striatum, and that greater reduction in BOLD response in regions of interest will predict decreased smoking.
• No functional magnetic resonance imaging (fMRI)
No functional magnetic resonance imaging (fMRI) serves as the control intervention to the fMRI intervention. Participants who are randomized to the no fMRI intervention or who have a contraindication to MRI will complete an identical cue-reactivity task in a cue-reactivity lab during the baseline and 24-hour follow-up test sessions.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change on Craving Questionnaire Score	At each visit (baseline, intervention sessions, and follow-up test sessions), participants will complete a Craving Questionnaire survey at multiple timepoints during each visit (baseline, and after each cue exposure). The craving questionnaire lists four statements about craving for cigarettes (e.g., "I have an urge for a cigarette"), and the participants rate how they agree with the statements at that moment on a scale of 1 to 5 (1 = strongly disagree and 5 = strongly agree). This measure will examine the change in behavioral response to cues over the course of the study, and differences in response between the R-E arms and NR-E arms.	Between Week 1 and Week 26
Primary	Mean Change on Mood Form Score	At each visit (baseline, intervention sessions, and follow-up test sessions), participants will complete a Mood Form survey at multiple timepoints during each visit (baseline, and after each cue exposure). The mood form lists nine moods or emotions (e.g., "Happy" or "Unhappy"), and the participants rate how they are experiencing the moods at that moment on a scale of 0 to 6 (0 = Not at all and 6 = Extremely). This measure will examine change in behavioral response to cues over the course of the study, and differences in response between the R-E arms and the NR-E arms.	Between Week 1 and Week 26
Primary	Mean Change in Heart Rate	At each visit (baseline, intervention sessions, and follow-up test sessions), study staff will collect participant heart rate at multiple timepoints during each visit (baseline, and after each cue exposure). Study staff will connect participants to a BIOPAC MP100 data acquisition system using two electrodes affixed to the participants' ribcage or wrists to collect this data. This measure will examine change in physiological response to cues over the course of the study, and differences in response between the R-E arms and NR-E arms.	Between Week 1 and Week 26
Primary	Mean Change in Skin Conductance	At each visit (baseline, intervention sessions, and follow-up test sessions), study staff will collect participant skin conductance at multiple timepoints during each visit (baseline, and after each cue exposure). Study staff will connect participants to a BIOPAC MP100 data acquisition system using two Ag/AgCI electrodes attached to the second phalanx of the first and third fingers of the participants' non-dominant hand to collect this data. This measure will examine change in physiological response to cues over the course of the study, and differences in response between the R-E arms and NR-E arms.	Between Week 1 and Week 26
Primary	Mean Change in Blood Pressure	At each visit (baseline, intervention sessions, and follow-up test sessions), study staff will collect participant blood pressure (both systolic and diastolic pressures) at multiple timepoints during each visit (baseline, and after each cue exposure). Study staff will connect participants to a non-invasive arm cuff to collect this data. This measure will examine change in physiological response to cues over the course of the study, and differences in response between the R-E arms and NR-E arms.	Between Week 1 and Week 26