Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging

NCT ID: NCT01664741

Last Updated: 2019-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2018-12-31

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.

Conditions

Nicotine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nicotine patch - transdermal

21 mg nicotine patch

Group Type: ACTIVE_COMPARATOR

Nicotine patch - transdermal

Intervention Type: DRUG

21 mg patch

Placebo NRT

Matching placebo patch

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Healthy non-smoker comparison

Demographically-matched women and men who have never smoked

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Nicotine patch - transdermal

21 mg patch

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Nicotine Replacement Therapy (NRT)

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary E McCaul, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01DA026823

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00036996

Identifier Type: -

Identifier Source: org_study_id