Behavioral Memory Modulation in Nicotine Addiction

April 24, 2025 updated by: Medical University of South Carolina

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
191

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: R-E (Retrieval Extinction)
83 anticipated participants will undergo 3 sessions on consecutive days of the Retrieval Extinction Training (RET) intervention consisting of a 5-minute 'retrieval' smoking-content video followed 10 minutes later by 1 hour of 'extinction' training consisting of four sequences of smoking-related cues (e.g., pictures). Participants will also receive a lab-based smoking-related cue-reactivity experience during the baseline assessment and 24-hour follow-up test.
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.
Other: NR-E (No R-E)
83 anticipated participants will undergo 3 sessions on consecutive days of the control Retrieval Extinction Training (RET) intervention consisting of a 5-minute 'retrieval' non-smoking or neutral-content video followed 10 minutes later by 1 hour of 'extinction' training consisting of four sequences of non-smoking or neutral cues (e.g., pictures). Participants will also receive a lab-based non-smoking or neutral cue-reactivity experience during the baseline assessment and 24-hour follow-up test.
Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Craving Questionnaire Score, Response to the Novel Cue
Time Frame: up to 24 weeks, Baseline, 24 hours, Weeks 2, 4, 6, 8, 12, and 24
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 is the average of 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 behavioral response to the novel cue over the course of the study, and differences in response between the R-E arms and NR-E arms.
up to 24 weeks, Baseline, 24 hours, Weeks 2, 4, 6, 8, 12, and 24
Mean Cigarettes Smoked Per Day
Time Frame: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Cigarettes Smoked per Day were recorded daily and summarized at follow-up visits
up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Smoking Days
Time Frame: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Cigarettes Smoking days were recorded daily and summarized at follow-up visits. The percentage of days since last follow up visit where smoking is recorded is reported
up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Mean Mood-Craving Response to the Novel Cue
Time Frame: up to 24 weeks, Baseline, 24 Hours, Weeks 2, 4, 6, 8, 12, and 24
At each visit (baseline, intervention sessions, and follow-up test sessions), participants will complete a mood craving during each visit. The mood craving form is a single item question ranging from 0 (no craving) to 100 (greatest craving possible). This measure will examine the behavioral response to the novel cue over the course of the study, and differences in response between the R-E arms and NR-E arms.
up to 24 weeks, Baseline, 24 Hours, Weeks 2, 4, 6, 8, 12, and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of South Carolina

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Saladin, PhD, Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 4, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 28, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 16, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 00069355
  • R01DA043587 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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