Gender Differences in Response to Nicotine Replacement Therapy and De-Nicotinized Cigarettes (BIRCWH)

• ClinicalTrials.gov Identifier: NCT00960778
• Recruitment Status: Completed
• First Posted: August 18, 2009
• Results First Posted: October 23, 2018
• Last Update Posted: October 23, 2018
• Sponsor: Medical University of South Carolina
• Information provided by (Responsible Party): Medical University of South Carolina

Study Description

Brief Summary:

This study will investigate the underlying neurobiology of differences between male and female smokers. Research suggests that women are less responsive to nicotine replacement therapy (NRT) than men and more responsive to the sensory and behavioral aspects of smoking. This study proposed that male smokers will have a greater response to NRT demonstrated by reduced withdrawal symptoms, craving, and less blood-oxygen-level dependent functional magnetic resonance imaging (BOLD FMRI) regional brain activation in response to nicotine-cues as compared to female smokers treated with NRT. Additionally, female smokers will have a greater response to denicotinized cigarettes with decreased withdrawal symptoms, craving, and less BOLD fMRI activation in response to nicotine-cues as compared to male smokers.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: nicotine patch (Nicoderm Committed Quitter (CQ), Habitrol); Other: denicotinized cigarettes (Quest 3 cigarettes)	Phase 2

Detailed Description:

Women smokers are less responsive to nicotine replacement therapy (NRT) and more responsive to environmental cues associated with smoking behavior. This pilot study is designed to increase understanding of the neural circuitry underlying these differences. In the proposed study, adult male and female (10 per group) treatment-seeking nicotine-dependent individuals will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues under three conditions during a seven day period: baseline, after NRT, and after denicotinized cigarette facilitated-extinction. After baseline scanning, subjects will receive three days of 21 mg nicotine patch. Scanning procedures will be repeated on day 3. Subjects will then receive denicotinized cigarettes for ad lib smoking on days three through seven. Subjects will be asked to remain abstinent throughout the study period and they will be assessed daily with self-report, Carbon Monoxide (CO) monitor and for nicotine withdrawal.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gender Differences in Response to Nicotine Replacement Therapy and De-Nicotinized Cigarettes
• Study Start Date: March 2009
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Women- denicotinized cigarette; Treatment-seeking nicotine-dependent women will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues after four days of denicotinized cigarette (less than 0.5 gram nicotine) use.	Other: denicotinized cigarettes (Quest 3 cigarettes); Cigarettes that contain trace levels of nicotine (less than .05 mg per cigarette) will be utilized ad lib in the study for 4 days after the nicotine patch.; Other Name: Quest 3 cigarettes
Experimental: Men- denicotinized cigarette; Treatment-seeking nicotine-dependent men will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues after four days of denicotinized cigarette (less than 0.5 gram nicotine) use.	Other: denicotinized cigarettes (Quest 3 cigarettes); Cigarettes that contain trace levels of nicotine (less than .05 mg per cigarette) will be utilized ad lib in the study for 4 days after the nicotine patch.; Other Name: Quest 3 cigarettes
Experimental: Women -nicotine patch; Treatment-seeking nicotine-dependent women will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues under after receiving three days of a 21 mg nicotine patch.	Drug: nicotine patch (Nicoderm Committed Quitter (CQ), Habitrol); Nicotine patch 21 mg every 24 hours will be utilized for the three days after the first scanning session.; Other Names: Nicoderm Committed Quitter (CQ); Habitrol; nicotine transdermal system; NRT
Experimental: Men- nicotine patch; Treatment-seeking nicotine-dependent men will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues under after receiving three days of a 21 mg nicotine patch.	Drug: nicotine patch (Nicoderm Committed Quitter (CQ), Habitrol); Nicotine patch 21 mg every 24 hours will be utilized for the three days after the first scanning session.; Other Names: Nicoderm Committed Quitter (CQ); Habitrol; nicotine transdermal system; NRT

Outcome Measures

Primary Outcome Measures :

1. Post- Cue Exposure Craving Nicotine Patch [ Time Frame: Day 3 ]
   Participants will complete cue exposure sessions after 3 days of nicotine patch use and rate craving on a 10 item self-report questionnaire. The Within Sessions Rating scale measures craving with 0 indicating Not at All and 10 indicating Extremely.
2. Post- Cue Exposure Craving Denicotinized Cigarettes [ Time Frame: Day 7 ]
   Participants will complete cue exposure sessions after 4 days of denicotinized cigarette us and rate craving on a 10 item self-report questionnaire, the Questionnaire of Smoking Urges- Brief (QSU-B). Participants rate craving on a scale on a 1-7 point Likert scale where indicates Strongly Disagree and 7 indicates Strongly Agree. Higher scores indicate higher craving. Ratings from the 10 items are summed to attain the score reported here.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age 21 - 60.
2. Meet criteria for primary nicotine dependence, smoke at least 70% of days in the last 30 days prior to assessment.
3. Participants will have afternoon end-expired carbon monoxide levels of at least 15 p.p.m. to confirm smoke inhalation.
4. Moderate to high levels of nicotine dependence confirmed by Fagerstrom Test of Nicotine Dependence score.
5. General good health confirmed by history & physical, serum chemistries, complete blood count, urinalysis, and electrocardiogram.
6. Able to read and understand questionnaires and informed consent.
7. Right-handed.
8. Treatment seeking.
9. Demonstrate subjective response to cues in a laboratory cue reactivity session.
10. Able to maintain abstinence from nicotine during the study period.
11. Participants must have a negative rapid-screening Urine Drug Screen (UDS) and pregnancy test prior to both imaging sessions and placement of the patch.
12. Female participants will use a reliable method of birth control throughout the study.

Exclusion Criteria:

1. Currently meets Diagnostic and Statistical Manual (DSM)-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
2. Any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.
3. Use of other tobacco products.
4. Current use of nicotine replacement therapy or other smoking cessation treatment.
5. Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data.
6. Current suicidal ideation with plan or homicidal ideation.
7. Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications.
8. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit ability to participate in scan.
9. Sexually active females of child-bearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
10. Has current charges pending for a violent crime (not including Drive Under Influence (DUI) related offenses).
11. Persons with ferrous metal implants or pacemaker since fMRI will be used.
12. Persons who live with another smoker who is unwilling or unable to refrain from smoking in the home or presence of the participant.

Contacts and Locations

Locations

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

Investigators

• Principal Investigator: Karen Hartwell, MD; Medical University of South Carolina

More Information

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00960778
• Other Study ID Numbers: HR#18333
• First Posted: August 18, 2009
• Results First Posted: October 23, 2018
• Last Update Posted: October 23, 2018
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University of South Carolina:

gender; nicotine dependence; nicotine replacement therapy; extinction; denicotinized cigarettes

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action