Nicotine Dependence, Smoking, Cigarette, Smoking Cessation, Smoking Behaviors, Smoking Reduction, Craving
Conditions
Keywords
nicotine, craving, virtual reality cue exposure, smoking relapse, immersive video environment, extinction enhancer
Brief summary
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 intervention - informed by basic research - that may lead to a more effective and efficient treatment for smokers. The expected findings should provide initial effect size data for the addition of isradipine to an integrated psychosocial/behavioral and pharmacological smoking cessation intervention for smokers, and thus provide the necessary data for a large-scale follow-up trial.
Detailed description
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.
Interventions
DRUGIsradipine
Isradipine will be administered 90 minutes prior to the initiation of cue exposure.
BEHAVIORALCue Exposure
Participants will be exposed to visual smoking cues (i.e., immersive 360 degree video environments) delivered through consumer virtual reality headset and handle cigarette packs to activate and extinguish craving.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Study capsules will be prepared containing: (a) 15 mg immediate release isradipine or (b) pill placebo consisting of Avicel microcrystalline cellulose powder (non-digestible pass-through). Isradipine and placebo capsules will be identical in appearance to maintain the double-blind. Individual doses will be dispensed to participants by blinded personnel 75 m prior to the first cue exposure session and patients will be asked to remain in the clinic until session time.
Intervention model description
Participants will be randomized to receive isradipine (ISR) or placebo (PBO).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. 18-65 years old; 2. Willing and able to provide informed consent, attend all study visits, and comply with the protocol; 3. Daily smoker for at least one year; and 4. Currently smoke an average of at least 5 cigarettes per day.
Exclusion criteria
1. Current diagnosis of a psychotic, eating, developmental or bipolar disorder, or significant suicide risk; 2. Current treatment for smoking cessation or use of other nicotine products, including e-cigarettes; 3.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Craving Intensity to Smoking Cues | The outcome is measured in a medication-free cue exposure session conducted 24 hours after medication administration | Primary outcome measures will be craving intensity to smoking cues based on a scale from 0 (No craving) to 100 (Intense craving). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from January 2020 to June 2023 with a pause from March 2020 to December 2020 resulting from pandemic-related restrictions on research
Pre-assignment details
To be eligible for randomization, individuals had to abstain from smoking, starting 24 hours prior to the treatment visit. Prior to randomization at the treatment visit, individuals who reported smoking or had carbon monoxide level that exceeded 4 ppm were ineligible to participate that day but could reschedule.
Participants by arm
| Arm | Count |
|---|---|
| Isradipine Participants will receive 15mg of immediate release isradipine.
Isradipine: Isradipine will be administered 90 minutes prior to the initiation of cue exposure.
Cue Exposure: Participants will be exposed to visual smoking cues (i.e., immersive 360 degree video environments) delivered through consumer virtual reality headset and handle cigarette packs to activate and extinguish craving. | 40 |
| Placebo Participants will receive a placebo pill identical in appearance to isradipine.
Cue Exposure: Participants will be exposed to visual smoking cues (i.e., immersive 360 degree video environments) delivered through consumer virtual reality headset and handle cigarette packs to activate and extinguish craving. | 38 |
| Total | 78 |
Baseline characteristics
| Characteristic | Placebo | Isradipine | Total |
|---|---|---|---|
| Age, Continuous | 44.76 years STANDARD_DEVIATION 10.12 | 41.10 years STANDARD_DEVIATION 12.14 | 42.88 years STANDARD_DEVIATION 11.28 |
| Craving intensity to smoking cues | 60.39 units on a scale STANDARD_DEVIATION 3.83 | 51.13 units on a scale STANDARD_DEVIATION 3.73 | 55.76 units on a scale STANDARD_DEVIATION 3.78 |
| Education level College Graduate | 14 Participants | 14 Participants | 28 Participants |
| Education level Graduate School | 6 Participants | 4 Participants | 10 Participants |
| Education level High School Graduate | 7 Participants | 7 Participants | 14 Participants |
| Education level Partial College | 11 Participants | 13 Participants | 24 Participants |
| Education level Partial High School | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 35 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 31 Participants | 64 Participants |
| Region of Enrollment United States | 38 participants | 40 participants | 78 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 23 Participants | 25 Participants | 48 Participants |
| Years of daily smoking | 23.42 years STANDARD_DEVIATION 11.32 | 20.53 years STANDARD_DEVIATION 12.23 | 21.94 years STANDARD_DEVIATION 11.81 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 38 |
| other Total, other adverse events | 15 / 40 | 4 / 38 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 |
Outcome results
Primary
Craving Intensity to Smoking Cues
Primary outcome measures will be craving intensity to smoking cues based on a scale from 0 (No craving) to 100 (Intense craving).
Time frame: The outcome is measured in a medication-free cue exposure session conducted 24 hours after medication administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isradipine | Craving Intensity to Smoking Cues | 40.50 units on a scale | Standard Error 3.54 |
| Placebo | Craving Intensity to Smoking Cues | 50.44 units on a scale | Standard Error 3.59 |