Nicotine Use Disorder
Conditions
Brief 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.
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.
Interventions
BEHAVIORALRetrieval 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.
BEHAVIORALControl 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.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Craving Questionnaire Score, Response to the Novel Cue | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Smoking Days | 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 |
| Mean Mood-Craving Response to the Novel Cue | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 81 |
| 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. | 82 |
| Total | 163 |
Baseline characteristics
| Characteristic | NR-E (No R-E) | Total | R-E (Retrieval Extinction) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants | 157 Participants | 79 Participants |
| Age, Continuous | 48.5 years STANDARD_DEVIATION 11 | 48.2 years STANDARD_DEVIATION 11.2 | 47.9 years STANDARD_DEVIATION 11.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 33 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 67 Participants | 128 Participants | 61 Participants |
| Region of Enrollment United States | 82 participants | 163 participants | 81 participants |
| Sex: Female, Male Female | 41 Participants | 79 Participants | 38 Participants |
| Sex: Female, Male Male | 41 Participants | 84 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 82 |
| other Total, other adverse events | 0 / 81 | 0 / 82 |
| serious Total, serious adverse events | 0 / 81 | 0 / 82 |
Outcome results
Primary
Mean Cigarettes Smoked Per Day
Cigarettes Smoked per Day were recorded daily and summarized at follow-up visits
Time frame: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Population: study population includes all participants that returned for a follow up visit at 2-weeks post intervention or later.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 26 Weeks | 8.5 Average Cigarettes Smoked Per Day | Standard Deviation 11.9 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | Study Baseline | 9.4 Average Cigarettes Smoked Per Day | Standard Deviation 7.7 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 2 weeks | 7.2 Average Cigarettes Smoked Per Day | Standard Deviation 9 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 4 Weeks | 7.5 Average Cigarettes Smoked Per Day | Standard Deviation 6.6 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 6 weeks | 8.1 Average Cigarettes Smoked Per Day | Standard Deviation 8.4 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 8 weeks | 8.3 Average Cigarettes Smoked Per Day | Standard Deviation 8.4 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 12 Weeks | 8.1 Average Cigarettes Smoked Per Day | Standard Deviation 8.2 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 16 weeks | 8.5 Average Cigarettes Smoked Per Day | Standard Deviation 10.8 |
| R-E (Retrieval Extinction) | Mean Cigarettes Smoked Per Day | 21 Weeks | 9 Average Cigarettes Smoked Per Day | Standard Deviation 11.6 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 16 weeks | 7.8 Average Cigarettes Smoked Per Day | Standard Deviation 7 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 8 weeks | 7.7 Average Cigarettes Smoked Per Day | Standard Deviation 6.5 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | Study Baseline | 10.1 Average Cigarettes Smoked Per Day | Standard Deviation 7.7 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 26 Weeks | 7.1 Average Cigarettes Smoked Per Day | Standard Deviation 6.5 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 2 weeks | 6.7 Average Cigarettes Smoked Per Day | Standard Deviation 6.7 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 12 Weeks | 7.7 Average Cigarettes Smoked Per Day | Standard Deviation 6.3 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 4 Weeks | 8.2 Average Cigarettes Smoked Per Day | Standard Deviation 8.5 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 21 Weeks | 7.5 Average Cigarettes Smoked Per Day | Standard Deviation 6.6 |
| NR-E (No R-E) | Mean Cigarettes Smoked Per Day | 6 weeks | 7.9 Average Cigarettes Smoked Per Day | Standard Deviation 7.1 |
Primary
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.
Time frame: up to 24 weeks, Baseline, 24 hours, Weeks 2, 4, 6, 8, 12, and 24
Population: Participant included are those randomized to study treatment and return for at least 1 study visit. Mean response to the 4 CQ items and standard deviations to the novel cues are listed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | Study Baseline | 3.43 score on a scale, average of 4 responses | Standard Deviation 0.99 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 24 Hours | 2.55 score on a scale, average of 4 responses | Standard Deviation 1.16 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 2 Weeks | 2.40 score on a scale, average of 4 responses | Standard Deviation 0.95 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 4 Weeks | 2.49 score on a scale, average of 4 responses | Standard Deviation 0.99 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 6 Weeks | 2.33 score on a scale, average of 4 responses | Standard Deviation 1.04 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 8 Weeks | 2.39 score on a scale, average of 4 responses | Standard Deviation 0.95 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 12 Weeks | 2.21 score on a scale, average of 4 responses | Standard Deviation 1.08 |
| R-E (Retrieval Extinction) | Mean Craving Questionnaire Score, Response to the Novel Cue | 24 Weeks | 1.96 score on a scale, average of 4 responses | Standard Deviation 1.03 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 24 Weeks | 1.97 score on a scale, average of 4 responses | Standard Deviation 0.99 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 24 Hours | 2.88 score on a scale, average of 4 responses | Standard Deviation 1.07 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | Study Baseline | 3.73 score on a scale, average of 4 responses | Standard Deviation 0.96 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 6 Weeks | 2.42 score on a scale, average of 4 responses | Standard Deviation 1.05 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 12 Weeks | 2.31 score on a scale, average of 4 responses | Standard Deviation 1.12 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 2 Weeks | 2.59 score on a scale, average of 4 responses | Standard Deviation 1.14 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 8 Weeks | 2.25 score on a scale, average of 4 responses | Standard Deviation 1.06 |
| NR-E (No R-E) | Mean Craving Questionnaire Score, Response to the Novel Cue | 4 Weeks | 2.60 score on a scale, average of 4 responses | Standard Deviation 1.09 |
Secondary
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.
Time frame: up to 24 weeks, Baseline, 24 Hours, Weeks 2, 4, 6, 8, 12, and 24
Population: Participant included are those randomized to study treatment and return for at least 1 study visit. Mean mood-Craving response and standard deviations to the novel cues are listed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 24 Weeks | 23.1 score on a scale, 0-100 | Standard Deviation 27.1 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | Study Baseline | 62.1 score on a scale, 0-100 | Standard Deviation 29.2 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 24 Hours | 38.1 score on a scale, 0-100 | Standard Deviation 29.7 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 2 Weeks | 32.3 score on a scale, 0-100 | Standard Deviation 26.5 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 4 Weeks | 33.1 score on a scale, 0-100 | Standard Deviation 29.6 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 6 Weeks | 29.7 score on a scale, 0-100 | Standard Deviation 27.4 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 8 Weeks | 31.8 score on a scale, 0-100 | Standard Deviation 25.1 |
| R-E (Retrieval Extinction) | Mean Mood-Craving Response to the Novel Cue | 12 Weeks | 29.6 score on a scale, 0-100 | Standard Deviation 27.6 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 12 Weeks | 31.3 score on a scale, 0-100 | Standard Deviation 29.4 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 24 Weeks | 23.3 score on a scale, 0-100 | Standard Deviation 29.6 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 4 Weeks | 33.4 score on a scale, 0-100 | Standard Deviation 31.2 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | Study Baseline | 69.5 score on a scale, 0-100 | Standard Deviation 24.2 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 8 Weeks | 30.5 score on a scale, 0-100 | Standard Deviation 29.6 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 24 Hours | 46.5 score on a scale, 0-100 | Standard Deviation 29.1 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 6 Weeks | 31.1 score on a scale, 0-100 | Standard Deviation 29.3 |
| NR-E (No R-E) | Mean Mood-Craving Response to the Novel Cue | 2 Weeks | 33.5 score on a scale, 0-100 | Standard Deviation 31.6 |
Secondary
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
Time frame: up to 26 weeks, Baseline, Weeks 2, 4, 6, 8, 12, 16, 21 and 26
Population: study population includes all participants that returned for a follow up visit at 2-weeks post intervention or later.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| R-E (Retrieval Extinction) | Percentage of Smoking Days | Study Baseline | 98.5 percentage of days reported smoking | Standard Deviation 5.3 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 12 Weeks | 73.2 percentage of days reported smoking | Standard Deviation 41.7 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 4 Weeks | 76.1 percentage of days reported smoking | Standard Deviation 39.2 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 16 weeks | 68.2 percentage of days reported smoking | Standard Deviation 43.8 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 6 weeks | 77.1 percentage of days reported smoking | Standard Deviation 38.9 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 21 Weeks | 64.8 percentage of days reported smoking | Standard Deviation 46.4 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 8 weeks | 77 percentage of days reported smoking | Standard Deviation 37.5 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 26 Weeks | 62.4 percentage of days reported smoking | Standard Deviation 44.4 |
| R-E (Retrieval Extinction) | Percentage of Smoking Days | 2 weeks | 72.5 percentage of days reported smoking | Standard Deviation 37.8 |
| NR-E (No R-E) | Percentage of Smoking Days | 26 Weeks | 66.2 percentage of days reported smoking | Standard Deviation 42.7 |
| NR-E (No R-E) | Percentage of Smoking Days | 2 weeks | 70.2 percentage of days reported smoking | Standard Deviation 40 |
| NR-E (No R-E) | Percentage of Smoking Days | 4 Weeks | 74.7 percentage of days reported smoking | Standard Deviation 39.4 |
| NR-E (No R-E) | Percentage of Smoking Days | Study Baseline | 98.1 percentage of days reported smoking | Standard Deviation 10.5 |
| NR-E (No R-E) | Percentage of Smoking Days | 6 weeks | 73.8 percentage of days reported smoking | Standard Deviation 40 |
| NR-E (No R-E) | Percentage of Smoking Days | 8 weeks | 75.1 percentage of days reported smoking | Standard Deviation 39 |
| NR-E (No R-E) | Percentage of Smoking Days | 12 Weeks | 74 percentage of days reported smoking | Standard Deviation 37.4 |
| NR-E (No R-E) | Percentage of Smoking Days | 16 weeks | 70.7 percentage of days reported smoking | Standard Deviation 42.5 |
| NR-E (No R-E) | Percentage of Smoking Days | 21 Weeks | 67.9 percentage of days reported smoking | Standard Deviation 41.6 |