Isradipine enhancement of virtual reality cue exposure for smoking cessation: Rationale and study protocol for a double-blind randomized controlled trial.

Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. 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 design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment.
Competing Interests: Declaration of Competing Interest A. Perrone, C. Gebhardt, J. Roache, and C. Young report no conflict of interests with their funding. S. Papini receives support from the National Institutes of Health and the Donald D. Harrington Foundation. H. Morikawa receives support from the National Institutes of Health. M. Otto receives support from the National Institutes of Health and compensation as a speaker and Chair of the Scientific Advisory Board for Big Health. J. Smits receives support from the National Institutes of Health, compensation for his work as a consultant to Big Health, as editor for Elsevier and the American Psychological Association, and royalties from various book publishers. The authors declared that these funding organizations had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
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