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Trial record 31 of 181 for:    RET

Behavioral Memory Modulation in Nicotine Addiction

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ClinicalTrials.gov Identifier: NCT03744559
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : February 15, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Michael Saladin, Medical University of South Carolina

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.

Condition or disease Intervention/treatment Phase
Nicotine Use Disorder Behavioral: Retrieval Extinction Training (RET) Behavioral: Control Retrieval Extinction Training (RET) Other: Functional magnetic resonance imaging (fMRI) Other: No functional magnetic resonance imaging (fMRI) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 166 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : February 4, 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Experimental: R-E (Retrieval Extinction) with no fMRI
49 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 that is equivalent to the task that the R-E with fMRI arm receives in the fMRI scanner. This arm participates in the no functional magnetic resonance imaging (fMRI) 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.

Other: 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.

Experimental: R-E (Retrieval Extinction) with fMRI
34 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 smoking-related cue-reactivity experience in an fMRI scanner during the baseline assessment and 24-hour follow-up test. This arm participates in the functional magnetic resonance imaging (fMRI) 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.

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.

NR-E (No R-E) with no fMRI
49 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 that is equivalent to the task that the NR-E with fMRI arm receives in the fMRI scanner. This arm participates in the no functional magnetic resonance imaging (fMRI) intervention.
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.

Other: 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.

NR-E (No R-E) with fMRI
34 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 non-smoking or neutral cue-reactivity experience in an fMRI scanner during the baseline assessment and 24-hour follow-up test. This arm participates in the functional magnetic resonance imaging (fMRI) intervention.
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.

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.




Primary Outcome Measures :
  1. Mean Change on Craving Questionnaire Score [ Time Frame: Between Week 1 and Week 26 ]
    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.

  2. Mean Change on Mood Form Score [ Time Frame: Between Week 1 and Week 26 ]
    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.

  3. Mean Change in Heart Rate [ Time Frame: Between Week 1 and Week 26 ]
    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.

  4. Mean Change in Skin Conductance [ Time Frame: Between Week 1 and Week 26 ]
    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.

  5. Mean Change in Blood Pressure [ Time Frame: Between Week 1 and Week 26 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03744559


Contacts
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Contact: Emily Burns 843-792-6984 burnsemi@musc.edu
Contact: Mary Elizabeth Mira 843-792-2286 miram@musc.edu

Locations
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United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Michael Saladin, Ph.D.         
Sponsors and Collaborators
Medical University of South Carolina
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Michael Saladin, PhD Medical University of South Carolina

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Responsible Party: Michael Saladin, Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT03744559     History of Changes
Other Study ID Numbers: 00069355
R01DA043587 ( U.S. NIH Grant/Contract )
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action