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

Abstract

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 in a medication-free state 24 h later. 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.

Virtual Reality Technology Use in Cigarette Craving and Smoking Interventions (I “Virtually” Quit): Systematic Review

“…However, more research on the effects of VR-CET in combination with NRT is needed to confirm and nuance this hypothesis. It will be interesting to see the results from one of the protocol papers, which outlined a planned clinical trial that combined VR-CET with NRT (eg, see the study by Papini et al [ 79 ]). This study will have a larger number of participants (n=102 vs n=41 [ 20 ] and n=7 [ 21 ]), and although it does not propose a multisession VR-CET intervention or a follow-up measure, it will still be interesting to see if the results from this intervention are in line with previous findings.…”

“…Given the underwhelming results that were achieved by VR-CET in terms of smoking cessation, future studies might want to explore the potential of alternative interventions. However, at present, the interest in VR-CET does not appear to have waned yet, as shown by the number of recent studies that attempt to obtain results by combining VR-CET with other therapies, such as CBT [ 42 , 89 ] and NRT [ 20 , 79 ]. It is possible that combining VR-CET with other interventions will result in a more successful intervention, as multiple aspects of nicotine addiction are addressed.…”

“…Three other types of intervention with a behavioral component emerged: AAT-based [ 79 , 80 ], gamified behavioral training [ 56 , 83 - 85 ], and skill training [ 86 , 87 ]. The proof of concept has been provided for VR-AAT [ 81 , 82 ], and the 2 immersive games based on AAT demonstrated some success [ 56 , 83 , 84 ].…”

Clinical Relevance of Immersive Virtual Reality in the Assessment and Treatment of Addictive Disorders: A Systematic Review and Future Perspective

“…To evaluate the (cost-)effectiveness, relevant RCTs (level VR3), including adequate follow-up periods, need to be conducted. During our literature review, we identified five study protocols that report on planned RCTs and insights into potential new treatment mechanisms [77][78][79][80][81]. The studies focus on approach-avoidance training, mindfulness-based relapse prevention, memory-retrieval extinction and the use of pharmacotherapy (Isradipine) to enhance the effect of VRET on the extinction of craving.…”

Virtual Reality Technology Use in Cigarette Craving and Smoking Interventions (I “Virtually” Quit): Systematic Review (Preprint)

“…However, more research on the effects of VR-CET in combination with NRT is needed to confirm and nuance this hypothesis. It will be interesting to see the results from one of the protocol papers, which outlined a planned clinical trial that combined VR-CET with NRT (eg, see the study by Papini et al [79]). This study will have a larger number of participants (n=102 vs n=41 [20] and n=7 [21]), and although it does not propose a multisession VR-CET intervention or a follow-up measure, it will still be interesting to see if the results from this intervention are in line with previous findings.…”