Clinical trial NCT02595749
Conditions: Nicotine Dependence Tobacco Smoking
Sponsor: University of Southern California
Start date: 2016-07-01; Completion date: 2019-07-01
Enrollment: 83 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Socioemotional processing dysfunctions (i.e., disruptions in affective, cognitive, and neural processes that encode, interpret, and respond to socially and emotionally relevant stimuli) have been implicated in tobacco smoking and relapse, however this potential target for medication development has not been systematically examined. Evidence from animal and human laboratories indicate that administration of intranasal oxytocin enhances socioemotional processing and may be efficacious for the treatment of drug addiction, including nicotine dependence. In order to evaluate the potential efficacy of intranasal oxytocin for smoking cessation, this laboratory-based proposal will examine whether intranasal oxytocin attenuates smoking lapse, nicotine withdrawal, and socioemotional processing disruptions in regular smokers following overnight abstinence.

Detailed description:

Arms: arm 1: Participants received a single placebo nasal spray (consisting of 4ml sterile saline \[Ocean Nasal Spray Solution\]) during the first experimental session, which occurred on a single day. After a 72 hour washout period, they then received a single 40 IU dose of Pitocin (oxytocin, USP; concentration = 10 IU/1 mL; PAR Pharmaceuticals, NY, USA) during the second experimental session, which occurred on a single day. All nasal spray solutions were transferred into two, 2 ml intranasal atomizers and administered in four sprays to each nostril over the course of 10 minutes. arm 2: Participants received a single 40 IU dose of Pitocin (oxytocin, USP; concentration = 10 IU/1 mL; PAR Pharmaceuticals, NY, USA) during the first experimental session, which occurred on a single day. After a 72 hour washout period, they then received a single placebo nasal spray (consisting of 4ml sterile saline \[Ocean Nasal Spray Solution\]) during the second experimental session, which occurred on a single day. All nasal spray solutions were transferred into two, 2 ml intranasal atomizers and administered in four sprays to each nostril over the course of 10 minutes.
Interventions: intervention 1: Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
 
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Effects of Intranasal Oxytocin on Cigarette Smoking 
NCT02595749 
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Design Overview. The study will use a within-subjects design in which subjects will receive administrations of 
inOT (40 IU) and placebo. After an initial baseline session, participants will complete two experimental 
sessions at which an identical assessment battery of key outcomes will be administered. Session order will be 
counterbalanced and sessions will be separated by at least 5 days as a washout period. After completing all 
sessions participants will be debriefed.  
 
Participants. We will complete approximately 60 current smokers, recruiting via online and community 
advertisements.  
Inclusion Criteria: 1) Ages 18-40; 2) Smoke >= 10 cig/day for the past year; 3) English fluency. 
Exclusion Criteria: 1) Current DSM-5 substance use disorder, excluding nicotine dependence (to 
minimize alcohol or drug withdrawal symptoms during the study sessions); 2) Any medical condition that would 
increase risk for study participation (such as sinus infection or other condition blocking access to the olfactory 
epithelium); 3) Women who are pregnant or nursing; 4) Current use of psychiatric medication; 5) Breath 
Carbon Monoxide (CO) levels < 10ppm measured during study intake (to exclude individuals who overreport 
smoking in order to participate in the study); 6) Planning to quit or reduce smoking in the next 30 days; and 7) 
Current regular use of other nicotine products.  
 
Procedures 
Experimental sessions: Sessions will be conducted sometime between 9:00 AM and 3:00 PM. Upon 
reporting to the lab, participants will provide breath samples to confirm abstinence from smoking as well as 
alcohol, urine samples to test for drugs and womens’ urine samples will also be used to test for pregnancy. 
Sessions will be rescheduled if the participant provides a positive breath alcohol reading or a breath CO > 9 
ppm.  
At 9:15 AM, baseline cardiovascular measures (i.e., heart rate and blood pressure) will be obtained, and 
participants will complete self-report mood, withdrawal, and craving questionnaires. At 9:45 AM, participants 
will self-administer the intranasal spray. Cardiovascular and subjective measures will then be obtained 
repeatedly at 10:20, 10:50, and 11:20.  
At 11:40 PM, they will begin the Smoking Lapse Analogue task, which begins with a 50-min delay period 
and ends with a 60-min self-administration period. After, participants will rest for an additional 60 min and then 
the final cardiovascular and self-report measures will be obtained (at 2:50 PM). Around 3:00PM, participants 
will be discharged.  
inOT preparation and administration: inOT and placebo doses will be prepared by the USC Hospital’s 
investigational pharmacy within 24 hours of use. All waste will be discarded, and no doses will be reused or 
stored longer than 24 hours. IN Placebo will consist of 4ml sterile saline (0.9% provided by USC pharmacy) 
and will be transferred into four, 1 ml intranasal atomizers (see figure: MAD100 by LMA Inc., San Diego, CA). 
Nasal sprays will be self-administered in four doses to each nare over the course of 15 minutes. 
 
Experimental Session Measures 
 Cardiovascular and Subjective. The following measures will be given to all participants before the first 
intranasal spray administration and at repeated intervals thereafter. Heart rate and blood pressure will be 
assessed via a digital monitor as a physiological measure of withdrawal. Subjective measures will instruct 
participants to respond based on how they feel “right now.” The Profile of Mood States (POMS) lists 72 
affective adjectives that are rated on 4-point and includes subscales for subjective experiences (e.g., anxious). 
The Minnesota Nicotine Withdrawal Scale (MNWS) measures 11 DSM withdrawal symptoms on 6-point Likert-
type scales. The MNWS total score will serve as the primary composite measure of subjective withdrawal. The 
10-item Brief Questionnaire of Smoking Urges (QSU) measures desire, intention, urge, and need to smoke.  
 
Smoking Lapse Analogue Task: This task measures ability to resist the temptation to initiate smoking 
under conditions in which it is advantageous to remain abstinent. Following the second intranasal spray, 
participants will be presented with a tray containing 8 cigarettes of their preferred brand, a lighter, and an 
ashtray. This task begins with the delay period, during which participants will be instructed that they can 
commence smoking at any point over the next 50 min, but that for each 5 min they delay smoking, they will 
earn between $0.20 to $0.50 (this $ value has shown sensitivity to abstinence in our prior work using smokers 
from the Los Angeles area). Thus, participants can earn between $2 to $5 during the delay period. When 
participants “give in” and indicate they want to initiate smoking (or at the end of 50 min for those who choose 
not to smoke), they begin the self-administration period. During this period, participants will be told they can 


 
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now smoke as little or as much as they wish over the next 60 min, that they start with a monetary credit ranging 
between $1.60 to $4.00, and that for each cigarette they light, it will cost them $0.20 to $0.50. At the end of 
self-administration, participants enter a rest period (with no smoking) that lasts until the final assessment. 
Including the rest period is necessary to prevent an impending opportunity to smoke once they leave the 
laboratory, which could reduce smoking during the delay and self-administration periods. The number of 
minutes before participants begin smoking is the primary outcome (“delay score”; range 0-50).  
Data Analysis. We hypothesize that inOT will: 1) increase the “delay score” on the Smoking Lapse 
Analogue Task (Primary Aim 1); and 2) attenuate smoking urge and nicotine withdrawal (Primary Aim 2). For 
Primary Aim 1, we will analyze “delay score” data from the placebo and active inOT sessions using mixed 
linear models (MLMs). Drug (placebo, 40 IU inOT) will be an independent effect and we will control for session 
order, and sex. For Primary Aim 2, we will conduct similar analyses with the addition of time as an independent 
factor for all within-session repeated measures (e.g., subjective-effects).