2013 — 2015 |
Otto, Michael W. Smits, Jasper Zvolensky, Michael J. (co-PI) [⬀] |
R34Activity Code Description: To provide support for the initial development of a clinical trial or research project, including the establishment of the research team; the development of tools for data management and oversight of the research; the development of a trial design or experimental research designs and other essential elements of the study or project, such as the protocol, recruitment strategies, procedure manuals and collection of feasibility data. |
Enhancing Panic and Smoking Reduction Treatment With D-Cycloserine @ University of Texas, Austin
DESCRIPTION (provided by applicant): Approximately 9-15 million smokers in the U.S. meet criteria for at least one anxiety disorder during their lifetime (Kessler et al., 2005) and these persons experience significant challenges quitting tobacco (Piper et al., 2010a; Zvolensky et al., 2008). Yet, little attention has been given to the maintenance of tobacco use among persons with anxiety disorders, and in particular, smokers with a history of panic attacks. This group is especially important to study because research shows that they have significantly lower quit rates than smokers with no history of panic attacks, and that they respond the same to placebo, single cessation, and combination cessation pharmacotherapy (Piper et al., 2010a). The goal of the current research is to pilot test the efficacy of the addition of d-cycloserine (DCS) versus pil placebo to a cognitive-behavioral program (CBT) targeting the role of anxiety sensitivity, distress intolerance, and panic attacks in smoking maintenance. The proposed project builds directly from our basic and clinical research as well as corresponding pilot work on (a) tobacco-panic relations; (b) intensive cognitive-behavioral intervention (CBT) for panic- and anxious-prone smokers; and (c) DCS enhancement of CBT for panic reduction. The project aims to obtain initial effect sizes and perform an initial test of putative mechanisms of our specialized behavioral group protocol, Panic and Smoking Reduction Treatment (PSRT), combined with DCS as compared to PSRT plus placebo. The PSRT program integrates interceptive exposure, cognitive restructuring, and psycho education exercises with standard smoking cessation strategies and nicotine replacement therapy. Adult smokers (n = 80) with panic attacks will be recruited and randomly assigned to either: (1) PSRT plus DCS or (2) PSRT plus pill placebo. Primary outcome measures will be point prevalence abstinence, time to first smoking lapse, and time to smoking relapse, assessed at 2, 4, 8, 10, 16, and 24 weeks after quit date. Proposed mediators include panic attacks, distress intolerance, anxiety sensitivity, nicotine withdrawal symptoms, and negative effect. These variables will be assessed at baseline, weekly during the treatment phase, and at 2, 4, 8, 10, 16, and 24 weeks after quit date. The proposed study represents a crucial and important stage in translating basic research to strategies for treating nicotine dependence. The investigation addresses an important public health issue by testing an integrated intervention --- informed by basic research --- that may lead to a more effective and efficient treatment for at-risk smokers while simultaneously isolating explanatory mechanisms. The expected findings should: (1) guide advances in the theoretical conceptualization of the mechanisms involved in panic- and anxiety-smoking relations; and (2) provide initial effect size data for the addition of DCS to an integrated psychosocial/behavioral and pharmacological smoking cessation intervention for smokers with panic attacks, and thus provide the necessary data for a large-scale follow-up trial.
|
0.915 |
2014 — 2016 |
Smits, Jasper |
R34Activity Code Description: To provide support for the initial development of a clinical trial or research project, including the establishment of the research team; the development of tools for data management and oversight of the research; the development of a trial design or experimental research designs and other essential elements of the study or project, such as the protocol, recruitment strategies, procedure manuals and collection of feasibility data. |
3/3-Dose Timing of D-Cycloserine to Augment Cbt For Social Anxiety Disorder @ University of Texas, Austin
DESCRIPTION (provided by applicant): This application is in response to PAR-12-071: Collaborative R34s for Pilot Studies of Innovative Treatments in Mental Disorders (Collaborative R34). D-cycloserine (DCS) is a partial N-methyl-D-aspartate glutamate agonist that has been shown to enhance exposure therapies for anxiety disorders. This approach is grounded in recent research advances in understanding the neural circuitry underlying fear extinction and is based upon one of the striking successes of translational research. All human clinical studies to date have administered DCS at least 1 hour prior to the exposure sessions. This dose-timing strategy limits the clinical utility of this highly promising augmentation strategy, especially sine accumulating research suggest that the efficacy of DCS for enhancing exposure therapy outcomes may depend on the success of exposure sessions. Pre-clinical and initial clinical data suggest that the DCS exposure-augmentation effect can also be obtained when DCS is administered immediately after an extinction trial when it follows successful exposure sessions. The proposed study builds upon this extant research by testing the efficacy of tailored post-session DCS administration (i.e., only following successful exposure sessions) for augmenting exposure therapy. In order to maintain high internal validity in this R34 study, we will enroll patients with social anxiety disorder (SAD) in a previously validated 5-session CBT protocol and randomize them to: (1) tailored post-session DCS administration; (2) pre-session DCS administration; (3) placebo administration; or (4) non-tailored post-session DCS administration. The primary outcomes will be short- and long-term improvements in social anxiety severity: We expect that the tailored post-session DCS administration condition will outperform the pre-session DCS administration, placebo administration, and non-tailored post-session DCS administration conditions, respectively, at posttreatment, 1-month and 3-month follow-up. In addition, we will explore potential moderators of the efficacy of tailored post-session DCS administration for augmenting exposure therapy. This application is the logical next step in the study of DCS. It provides an important innovative move toward the realization of personalized medicine by providing the first step in the eventual development of an algorithm for administering DCS in CBT with the goal of maximizing the efficacy and cost-effectiveness of therapy for anxiety disorders, which are some of the most prevalent mental conditions, making this a project of potentially high public health significance.
|
0.915 |
2017 — 2019 |
Smits, Jasper |
R34Activity Code Description: To provide support for the initial development of a clinical trial or research project, including the establishment of the research team; the development of tools for data management and oversight of the research; the development of a trial design or experimental research designs and other essential elements of the study or project, such as the protocol, recruitment strategies, procedure manuals and collection of feasibility data. |
Approach Bias Retraining to Augment Smoking Cessation @ University of Texas, Austin
ABSTRACT Cigarette smoking remains a leading cause of preventable death1, contributing to over 480,000 deaths each year2. Although efficacious, standard care for smoking cessation is associated with high non-response rates, suggesting there is a need to develop augmentation strategies3. Theory and empirical findings suggest that targeting automated, impulsive, implicit processes may hold promise4?9. Specifically, retraining approach bias, or the approach action tendency toward stimuli related to the substance of interest has been effective in alcohol use disorders (i.e., reduction in relapse rates by 10%-13%)10?13. We recently extended this work to smoking by demonstrating that approach bias retraining reduced approach bias and the reduction in approach bias was associated with the number of days quit in the week following a self-guided quit attempt14. The goal of this application is to pilot test an intervention that integrates approach bias retraining with standard care for smoking cessation. The integrated intervention involves seven weekly 60-minute sessions. Each session involves 15 minutes of computerized approach bias retraining followed by 45 minutes of individual CBT. The target quit week is set at week 5, at which time nicotine replacement therapy is prescribed. Adult smokers (N=100) will be recruited and randomly assigned to (1) the integrated intervention or (2) a control intervention that combines standard smoking cessation care as described above with a computerized intervention that does not target approach bias. Abstinence will be assessed during the intervention (weeks 0- 7), at posttreatment (week 8), and at 1-month (week 9), 2-month (week 13) and 3-month (week 17) follow-up (i.e., post-quit). Measures of putative mediators will be assessed during the intervention (weeks 0-7). The proposed study represents a crucial and important stage in translating basic research to strategies for treating nicotine dependence. The investigation addresses an important public health issue by testing an integrated intervention - informed by basic research - that may lead to a more effective treatment for at-risk smokers while simulatenously isolating explanatory mechanisms. The expected findings should: (1) guide advances in the theoretical conceptualization of the mechanisms involved smoking; and (2) provide initial effect size data for the integrated smoking cessation intervention, and thus provide the necessary data for a large- scale follow-up trial.
|
0.915 |
2019 — 2020 |
Smits, Jasper Young, Cara Calloway |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Isradipine and Virtual Reality Cue Exposure For Smoking Cessation @ University of Texas, Austin
PROJECT SUMMARY/ABSTRACT Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. An estimated 8.6 million individuals live with chronic diseases caused by tobacco use, resulting in approximately $170 billion in direct medical costs, as well as $156 billion in lost productivity. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to identify targets involved in phase-specific challenges and design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. One key mechanism is subjective craving, which contributes to the maintenance of addiction and is also a risk factor for relapse. Pavlovian conditioning plays a role in craving among human smokers, who form strong associations between smoking and a variety of sensory cues. Among those who quit, memory traces of the rewarding properties of smoking endure and can be triggered by drug-associated cues even after prolonged abstinence. These associations can trigger strong cravings that increase the motivation to smoke and can lead to relapse. Thus, targeting drug-cue associations is key to the long-term impact on craving-induced relapse. Recent work in the Morikawa lab (consultant) tested pharmacologic augmentative strategies in rats using conditioned place preference (CPP), a Pavlovian learning model of cue-induced drug relapse. In a series of experiments, calcium channel blockage was identified as a key mechanism of action to enhance and prolong extinction of CPP. To translate these findings to humans, the current proposal will test isradipine, an FDA- approved calcium channel blocker, combined with cue exposure in an experimental therapeutics approach designed as an initial test of target engagement. To engage craving robustly in human participants, we will use multimodal smoking cues including innovative 360° video environments developed for this proposal and delivered through consumer virtual reality headsets. Adult smokers will be randomized to either: (1) cue exposure with isradipine (CE+ISR) or (2) cue exposure with placebo (CE+PBO). They will return 24-h later to repeat the procedure in a medication-free state. The target of engagement (subjective craving) will be measured after each of 10 trials during the two cue exposure sessions. The primary hypothesis will test whether isradipine enhances retention of craving extinction. A secondary exploratory aim will explore the feasibility and acceptability of implementation within a primary care setting where adult smokers receive healthcare. Findings will provide initial effect size data to determine whether target engagement is sufficient to warrant next stage research designed to evaluate the combined effect of isradipine and a cue exposure treatment on key clinical outcomes including smoking cessation and prolonged abstinence.
|
0.915 |