Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Johns Hopkins University
Information provided by (Responsible Party):
Mary E. McCaul, Johns Hopkins University Identifier:
First received: August 10, 2012
Last updated: February 23, 2016
Last verified: February 2016
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.

Condition Intervention Phase
Nicotine Dependence
Drug: Nicotine patch - transdermal
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging

Resource links provided by NLM:

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Mu-opioid receptor binding potential [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity (1/KD). Based on Zhou (2003), we use reference tissue graphical analysis (RTGA) (Schmitz, 2001) to obtain regional BP values using occipital lobe as a reference region (Schad, 2002).

Secondary Outcome Measures:
  • Nicotine craving [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Tiffany Questionnaire of Smoking Urges (QSU-brief)

  • Nicotine withdrawal [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Minnesota Nicotine Withdrawal Scale (MNWS)

Estimated Enrollment: 90
Study Start Date: April 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nicotine patch - transdermal
21 mg nicotine patch
Drug: Nicotine patch - transdermal
Other Name: Nicotine Replacement Therapy (NRT)
Placebo Comparator: Placebo NRT
Matching placebo patch
Drug: placebo
No Intervention: Healthy non-smoker comparison
Demographically-matched women and men who have never smoked

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 they 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.

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 21 - 60 years old
  • must meet DSM-IV criteria for nicotine dependence and be smoking 15 - 40 cigarettes/day

Exclusion Criteria:

  • BMI < 18 or > 30
  • DSM-IV criteria for a current or lifetime alcohol or drug use disorder; drug use in the last 90 days as determined by the TLFB; current alcohol consumption > 14 drinks/week; positive urine toxicology screen at initial assessment or before study procedures;
  • DSM-IV criteria for current depressive, anxiety or adjustment disorder and currently in need of or on psychotropic medications; we will not exclude subjects with a history of these disorders given the very high comorbidity of smoking and these psychiatric disorders.
  • DSM-IV criteria for Axis I psychotic disorder - lifetime (e.g., schizophrenia, bipolar disorder)
  • Presence of any serious medical condition; or have liver function tests more than 3 X normal;
  • History of any central nervous system disorder;
  • Abnormal MRI scan or history of significant closed head trauma;
  • Treatment with antidepressants, neuroleptics, sedative hypnotics, glucocorticoids, opiates within the last six months
  • Pregnancy, lactation, oral contraceptives or postmenopausal.
  • At least 5th grade reading level based on Shipley
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01664741

Contact: JoAnna Mathena, MA 410-955-9524

United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21205
Principal Investigator: Mary E McCaul, Ph.D.         
Sponsors and Collaborators
Johns Hopkins University
Principal Investigator: Mary E McCaul, Ph.D. Johns Hopkins University
  More Information

Responsible Party: Mary E. McCaul, Professor, Johns Hopkins University Identifier: NCT01664741     History of Changes
Other Study ID Numbers: R01DA026823 
Study First Received: August 10, 2012
Last Updated: February 23, 2016
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Nicotine dependence
nicotine replacement therapy
positron emission tomography

Additional relevant MeSH terms:
Tobacco Use Disorder
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Ganglionic Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Peripheral Nervous System Agents
Physiological Effects of Drugs processed this record on May 26, 2016