Clinical trial NCT01664741: Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
Official title: Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nicotine Dependence
Keywords: Nicotine dependence
cigarette
smoking
nicotine replacement therapy
positron emission tomography
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2012-08-14
Enrollment: 127
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to explain the differences in the prevalence of smoking in men and women, sex-specific differences in nicotine craving and withdrawal as well as the poorer therapeutic response to NRT. This work may pave the way to the design of improved pharmacotherapies that can more effectively target the endogenous opioid system in the treatment of nicotine dependence.

Detailed description: While smoking prevalence has declined for both men and women over the last two decades, rates among women have shown a much shallower decrease and, in recent years, prevalence of cigarette initiation has been higher for girls than boys. Smoking among women of child-bearing age has significant negative health consequences for mother and child, increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a quit attempt and more likely to relapse if these women do quit. Nicotine replacement therapy (NRT), still the most widely used smoking treatment intervention in the United States, is less effective for women compared with men, and women report less craving reduction on NRT. The endogenous opioid system is involved in smoking initiation, nicotine craving and reward as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic features of the endogenous mu-opioid system may in part explain gender differences in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT responses in women, this proposal will examine NRT effects on mu opioid receptor binding potential (MOR BP) in female compared to male smokers during active versus placebo NRT. Specifically, nicotine dependent women and men in active smoking status will undergo PET imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference group, demographically-matched women and men who have never smoked will undergo two scans as well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained repeatedly across the protocol. The proposed research will provide significant new, gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy.

Eligibility criteria: Inclusion Criteria:

* 21 - 60 years old
* must meet DSM-IV criteria for nicotine dependence and be actively smoking

Exclusion Criteria: subjects must meet study guidelines for medical and mental health status.

Primary outcomes:
measure: Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans
timeFrame: 90 minutes
Secondary outcomes:
measure: Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score
timeFrame: 72 hours
measure: Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score
timeFrame: 72 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Mary E McCaul, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: