Nicotine Use DisorderNCT03744559
Behavioral Memory Modulation in Nicotine Addiction
A study testing Retrieval Extinction Training (RET) in people with Nicotine Use Disorder, run by Medical University of South Carolina at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Use Disorder
- What is being tested?
- Retrieval Extinction Training (RET)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 191 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2019to 1 Nov 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and women, ages 25 to 65, who have smoked at least 10 cigarettes per day for at least 3 years.
- Participants must live within a 50-mile radius of the research facility and have reliable transportation.
- 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.
- 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).
Who cannot join
- Participants who are dependent on substances other than nicotine.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
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
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.
Read the 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.
- Conditions
- Nicotine Use Disorder
- Being tested
- Retrieval Extinction Training (RET), Control Retrieval Extinction Training (RET)
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrieval Extinction Training (RET)Behavioural
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)Behavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| R-E (Retrieval Extinction) | Experimental | 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. Receives: Behavioral: Retrieval Extinction Training (RET) |
| NR-E (No R-E) | Other | 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. Receives: Behavioral: Control Retrieval Extinction Training (RET) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Craving Questionnaire Score, Response to the Novel Cue
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.
Measured: up to 24 weeks, Baseline, 24 hours, Weeks 2, 4, 6, 8, 12, and 24
Mean Cigarettes Smoked Per Day
Cigarettes Smoked per Day were recorded daily and summarized at follow-up visits
Measured: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Secondary outcomes (2)
Percentage of Smoking Days
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
Measured: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Mean Mood-Craving Response to the Novel Cue
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.
Measured: up to 24 weeks, Baseline, 24 Hours, Weeks 2, 4, 6, 8, 12, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start4 Feb 2019
- Primary completion28 Oct 2023
- Study completion1 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 191 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Michael Saladin, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03744559
- Sponsor's protocol ID
- 00069355
- Other IDs
- R01DA043587
- Status last verified
- Apr 2025
- First submitted
- 13 Nov 2018
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03744559
- Acronym / sponsor ID
- 00069355
- Conditions
- Nicotine Use Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 191 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 28 Oct 2023 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 16 Nov 2018 (actual)
- Results
- Posted 18 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| R-E (Retrieval Extinction) | Experimental | Behavioral: Retrieval Extinction Training (RET)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. |
| NR-E (No R-E) | Other | Behavioral: Control Retrieval Extinction Training (RET)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. |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy men and women, ages 25 to 65, who have smoked at least 10 cigarettes per day for at least 3 years.
- Participants must live within a 50-mile radius of the research facility and have reliable transportation.
- 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.
- 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).
Key exclusion criteria (2 listed)
- Participants who are dependent on substances other than nicotine.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Behavioural | R-E (Retrieval Extinction) |
| 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. | Behavioural | NR-E (No R-E) |
Primary outcome
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.
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
2 secondary outcomes
Percentage of Smoking Days
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Saladin, PhD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Retrieval Extinction Training (RET) in people with Nicotine Use Disorder, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2025.