- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00390923
Testing a Full Substitution Therapy Approach As Treatment of Tobacco Dependence
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This pilot study utilizes a double-blind, two-armed design to evaluate the efficacy of combining oral selegiline with transdermal nicotine patch for smoking cessation in 40 nicotine-dependent smokers. After successful completion of 3 screening visits (to ensure medical and psychiatric eligibility criteria are met), subjects will be randomized into one of two experimental groups:
- selegiline (10 mg/day) + NRT (21 mg/24 hr)
- matching placebo + NRT (21 mg/24 hr)
Randomization will be performed through the use a random number list to generate 50% selegiline/50% placebo and also 50% male/50% female within each of those treatment groups.
Participants will begin selegiline (or placebo) once a day during Week 1, and dose will be graduated to full study dosage (10 mg/day) by adding an evening intake (a.m. and p.m. dosing) for Weeks 2-8. Day 15 of the trial represents target quit day and the transdermal nicotine patch (21 mg/24hr) will be applied at this time. Patches will be worn in conjunction with study medication for Weeks 3-8, after which the patch will be removed and study medication tapered throughout Week 9.
Subjects will present weekly to the Nicotine Dependence Clinic where they will provide breath, urine and blood samples as required, receive brief smoking cessation counseling and complete questionnaires regarding their smoking behavior and psychological state. A post-trial physical will be conducted upon completion of Week 9. Monthly follow-up phone interviews will be conducted for 5 months and subjects will be re-assessed in the NDC for a 6-month follow-up.
Trial Objectives
To determine if combination of selegiline hydrochloride and NRT (full substitution to tobacco) is superior to NRT alone + placebo (partial substitution) for smoking cessation in nicotine dependent smokers.
- The primary hypothesis is that full substitution (selegiline + NRT) will be superior to placebo + NRT for achievement of 7-day point prevalence smoking abstinence rates at the end of trial abstinence rates (Day 49-56) assessment in nicotine-dependent cigarette smokers.
- Secondary hypothesis 1a is that full substitution (selegiline + NRT) will be superior to NRT for achievement of last four weeks of trial (Days 29-56) smoking abstinence rates in nicotine-dependent cigarette smokers.
- Secondary hypothesis 1b is that full substitution (selegiline + NRT) will be superior to NRT for achievement 6-month post target quit date smoking abstinence rates in nicotine-dependent cigarette smokers.
To determine if treatment retention and study medication compliance will be higher in the full substitution (selegiline + NRT) group as compared to the NRT group during the 8-week smoking cessation trial.
Hypothesis 2 is that treatment retention and study medication compliance will be higher in the full substitution (selegiline + NRT) group as compared to the NRT group during the 8-week smoking cessation trial.
To determine if full substitution (selegiline + NRT) reduces nicotine craving and withdrawal symptoms as compared to NRT group during the 8-week smoking cessation trial.
Hypothesis 3 is that full substitution treatment will lead to significant reductions in tobacco withdrawal and craving ratings compared to NRT group.
- To determine adverse events profile in nicotine-dependent smokers of the combination of selegiline and NRT as compared to NRT.
Hypothesis 4 is that selegiline in combination with NRT will be well-tolerated and that rates of adverse events will not be significantly different between subjects assigned to full substitution as compared to NRT group.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ontario
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Toronto, Ontario, Canada, M5S 2S1
- Centre for Addiction and Mental Health
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Meet DSM-IV criteria for nicotine dependence with FTND score > 5.
- Smoke at least 15 cigarettes (3/4 pack) daily (averaged over 1 week, in the past 1 month).
- At the time of initial evaluation, are motivated to quit smoking in the next 30 days.
- Have made at least one unsuccessful attempt to quit smoking in the past year.
- At baseline, have expired breath CO level > 10.
- Are between ages 18-70 years old.
- Weigh at least 100 lbs (45.5 kg, selegiline dose < 0.22 mg/kg).
- No previous use of nicotine replacement products in the one month prior to randomization.
- Have the capacity to give informed consent, and are English-speaking.
Exclusion Criteria:
- Have present or past diagnoses of schizophrenia, bipolar disorder, PTSD, BPD or major depressive illness.
- Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 6 months prior to randomization into the trial (based on clinical evaluation including self-report, and confirmed by positive urine).
- Demonstrate serious medical conditions (i.e. abnormal liver function [as evidenced by AST, ALT or bilirubin values 2x ULN], unstable cardiovascular disease, significant blood abnormalities).
- Exhibit or have history of clinical hypertension.
- Exhibit active peptic ulcer disease.
- Are pregnant, are trying to become pregnant, or are currently breastfeeding.
- Are on current medication regimes that include antidepressants, or sympathomimetic agents, or meperidine and other meperidine-opioids which may have interactions with selegiline.
- Known hypersensitivity to selegiline or NRT.
- Are from the same household as another study participant.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
|
Participants will begin selegiline once a day during Week 1, and dose will be graduated to full study dosage (10 mg/day) by adding an evening intake (a.m. and p.m. dosing) for Weeks 2-8.
Day 15 of the trial represents target quit day and the transdermal nicotine patch (21 mg/24hr) will be applied at this time.
Patches will be worn in conjunction with study medication for Weeks 3-8, after which the patch will be removed and study medication tapered throughout Week 9.
|
Placebo Comparator: 2
|
Participants will begin placebo once a day during Week 1, and dose will be graduated to full study dosage (10 mg/day) by adding an evening intake (a.m. and p.m. dosing) for Weeks 2-8.
Day 15 of the trial represents target quit day and the transdermal nicotine patch (21 mg/24hr) will be applied at this time.
Patches will be worn in conjunction with study medication for Weeks 3-8, after which the patch will be removed and study medication tapered throughout Week 9.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Seven-day point prevalence smoking abstinence at end of trial (abstinence based on self-reported smoking abstinence verified by CO levels < 10 ppm)
Time Frame: 9 weeks
|
9 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Last four weeks of Trial Continuous smoking abstinence rates (verified by CO < 10 ppm)
Time Frame: 4 weeks
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4 weeks
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Seven-day point prevalence smoking abstinence
Time Frame: end of treatment, six-month follow-up
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end of treatment, six-month follow-up
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Treatment retention (based on survival analysis and number of weeks a subject completes in the trial)
Time Frame: upon completion
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upon completion
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Time line follow back for cigarettes smoked, alcohol and caffeinated beverage use
Time Frame: Weeks 1-8; six-month follow-up
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Weeks 1-8; six-month follow-up
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Tobacco craving as assessed by Tiffany scale for smoking urges
Time Frame: Weeks 1, 4 and 8; 6-month follow-up
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Weeks 1, 4 and 8; 6-month follow-up
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DSM-IV nicotine withdrawal symptom checklist
Time Frame: Weeks 1, 4 and 8; 6-month follow-up
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Weeks 1, 4 and 8; 6-month follow-up
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Collaborators and Investigators
Collaborators
Publications and helpful links
General Publications
- Henningfield JE, Goldberg SR. Nicotine as a reinforcer in human subjects and laboratory animals. Pharmacol Biochem Behav. 1983 Dec;19(6):989-92. doi: 10.1016/0091-3057(83)90405-7.
- Stolerman IP, Shoaib M. The neurobiology of tobacco addiction. Trends Pharmacol Sci. 1991 Dec;12(12):467-73. doi: 10.1016/0165-6147(91)90638-9.
- Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF. Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav. 2001 Dec;70(4):515-30. doi: 10.1016/s0091-3057(01)00676-1.
- Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, Shea C, Alexoff D, MacGregor RR, Schlyer DJ, Zezulkova I, Wolf AP. Brain monoamine oxidase A inhibition in cigarette smokers. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14065-9. doi: 10.1073/pnas.93.24.14065.
- Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91. doi: 10.1016/0165-0173(93)90013-p.
- Robinson TE, Berridge KC. Incentive-sensitization and addiction. Addiction. 2001 Jan;96(1):103-14. doi: 10.1046/j.1360-0443.2001.9611038.x.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Tobacco Use Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Agents
- Enzyme Inhibitors
- Neuroprotective Agents
- Protective Agents
- Psychotropic Drugs
- Antidepressive Agents
- Ganglionic Stimulants
- Nicotinic Agonists
- Cholinergic Agonists
- Monoamine Oxidase Inhibitors
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Nicotine
- Selegiline
Other Study ID Numbers
- 170/2006
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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