The Gender-Sex Hormone Interface With Craving & Stress-Related Changes in Smoking (SCOR-III)

• ClinicalTrials.gov Identifier: NCT01576874
• Recruitment Status: Completed
• First Posted: April 13, 2012
• Results First Posted: December 17, 2018
• Last Update Posted: July 1, 2020
• Sponsor: Kevin Gray, MD
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Kevin Gray, MD, Medical University of South Carolina

Study Description

Brief Summary:

The purpose of the overall parent study is to determine the impact of gender and hormones (estradiol, progesterone, testosterone and cortisol) on responses to stress and smoking cues presented in daily, "real-world" cue presentations compared to a final cue session in a lab. In addition, in the portion of the study that incorporates clinical trials elements and is reported here, the study will examine the impact of a single dose of oxytocin (chemical produced in the body) versus placebo (inactive substance) on reactivity to a stress procedure (Trier Social Stress Task) in smokers.

The overall parent study involves a cue presentation technology known as "CREMA" (Cue Reactivity Ecologic Momentary Assessment) which delivers four daily cue presentations to you on a handheld device during your everyday routine. Additionally, the study involves daily collection of saliva samples for hormonal testing. These daily procedures will provide information about the role of cues and hormones in daily life. The clinical trial portion of the study (reported here) consists of measures collected within the laboratory.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: Oxytocin; Drug: placebo	Not Applicable

Detailed Description:

Despite considerable advances in treatment development, cigarette smoking remains the leading cause of preventable death in the United States, and most smokers engaged in treatment are unsuccessful in quitting. The burden of illness is disproportionately borne by female smokers, who are less responsive to cessation interventions than males. The relationships between stress, craving, and smoking behavior are recognized as key factors underlying gender differences in nicotine dependence, but must be better understood and characterized to yield avenues for interventions addressing this critical health disparity.

In prior and ongoing SCOR studies, our research team has demonstrated gender and menstrual cycle/sex hormone influences on reactivity to laboratory-presented cues. Building from these laboratory findings, we propose taking two important next steps: (1) evaluating the experience of craving in the "real world" natural environment of female and male smokers, and (2) examining the impact of a safe and novel pharmacological intervention (oxytocin) on stress reactivity in female and male smokers.

If, as hypothesized, gender, sex hormones, and oxytocin administration influence the relationships between stress, craving, and smoking behavior, the findings could substantially address a key gender-related health disparity. Such knowledge could also inform the development of gender-specific interventions to enhance female smokers' response to cessation treatments. Therefore, the knowledge to be gained from the proposed study may yield significant public health benefits.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Gender-Sex Hormone Interface With Craving & Stress-Related Changes in Smoking
• Study Start Date: June 2012
• Actual Primary Completion Date: May 2017
• Actual Study Completion Date: June 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: oxytocin; Participants will be administered 40 IUs of oxytocin nasal spray at one study visit.	Drug: Oxytocin; 40 IUs of oxytocin administered intranasally one time; Other Name: syntocinon
Placebo Comparator: placebo; Participants will be administered 40 IUs of placebo nasal spray at one study visit.	Drug: placebo; placebo administered intranasally one time

Outcome Measures

Primary Outcome Measures :

1. Craving Response to Trier Social Stress Task [ Time Frame: Immediately after the conclusion of the TSST ]

   The TSST is the gold standard for evoking stress response in the laboratory. The participant must deliver a speech as though speaking to a group of hiring managers. The participant has 5 min to prepare, then three individuals unfamiliar to the participant (the audience) enter the room and are seated; the participant is instructed give the speech (without notes). The speech is delivered for 5 min, then the participant is instructed to serially subtract 13 from 1,022 as quickly and accurately as possible. The mental math recitation continues for 5 min, and at its conclusion, the spokesperson instructs the participant to stop and be seated, and the audience leaves the room. The total time for the TSST is 15 min.

   The Craving Questionnaire (Carter & Tiffany, 2001) is the sum of 4 items, each rated 1-5 on a Likert scale, with total score ranging 4-20, and higher scores indicating higher craving.

Secondary Outcome Measures :

1. Stress Response to Trier Social Stress Task [ Time Frame: Immediately after the conclusion of the TSST ]

   The TSST is the gold standard for evoking stress response in the laboratory. The participant must deliver a speech as though speaking to a group of hiring managers. The participant has 5 min to prepare, then three individuals unfamiliar to the participant (the audience) enter the room and are seated; the participant is instructed give the speech (without notes). The speech is delivered for 5 min, then the participant is instructed to serially subtract 13 from 1,022 as quickly and accurately as possible. The mental math recitation continues for 5 min, and at its conclusion, the spokesperson instructs the participant to stop and be seated, and the audience leaves the room. The total time for the TSST is 15 min.

   The single stress item is derived from the CREMA Mood/Stress Assessment (Warthen & Tiffany, 2009), asking how stressed the participant felt at that time, on a 5-point Likert scale, ranging 1-5 with higher score indicating feeling more stressed

2. Cortisol Response to Trier Social Stress Task [ Time Frame: Immediately following the Trier Social Stress Task ]
   Cortisol measured immediately following the Trier Social Stress Task, to evaluate physiological stress response.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Females and males age 18 - 45 who smoke at least an average of 5 cigarettes per day for at least past 6 months
2. Females must be post menarche and pre-menopausal, have a regular menstrual cycle between 25 and 35 days, and, if recently pregnant, be at least three months post-delivery/breast feeding
3. Participants must submit a carbon monoxide sample of ≥ 5 ppm at their screening visit

Exclusion Criteria:

1. Any serious or unstable medical or psychiatric disorder that may, in the judgment of the study physician, interfere with study completion
2. Participants must not meet criteria for PTSD
3. Any medication (e.g., propranolol) that may interfere with psychophysiological (e.g., heart rate) monitoring
4. Current substance dependence other than nicotine and caffeine use, in the past month
5. Use of other tobacco products
6. Females must not be pregnant, breast feeding, status post hysterectomy or bilateral oophorectomy, or taking birth control or hormone replacement medication that would affect the menstrual cycle
7. Males must not be status post orchiectomy

Contacts and Locations

Locations

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Kevin Gray, MD

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Michael Saladin, PhD; Medical University of South Carolina
• Principal Investigator: Kevin M Gray, MD; Medical University of South Carolina

  Study Documents (Full-Text)

Documents provided by Kevin Gray, MD, Medical University of South Carolina:

Study Protocol and Statistical Analysis Plan  [PDF] January 12, 2016

More Information

• Responsible Party: Kevin Gray, MD, Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01576874
• Other Study ID Numbers: Pro00016931; P50DA016511 ( U.S. NIH Grant/Contract )
• First Posted: April 13, 2012
• Results First Posted: December 17, 2018
• Last Update Posted: July 1, 2020
• Last Verified: June 2020

Keywords provided by Kevin Gray, MD, Medical University of South Carolina:

nicotine dependence; hormones

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Oxytocin; Oxytocics; Reproductive Control Agents; Physiological Effects of Drugs