Selegiline as an Aid to Smoking Cessation

Condition(s) targeted: Nicotine Dependence

Intervention: Selegiline Transdermal System (STS) (Drug); Placebo (Drug); Brief Weekly Smoking Cessation Intervention (Behavior)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Department of Veterans Affairs

This research study of 246 participants is designed to determine if the selegiline transdermal system (STS - a drug administered in skin patch form), in combination with weekly brief behavioral therapy, is efficacious as an aid to quitting smoking in heavy smokers (those who smoke 20 or more cigarettes every day). It is a placebo-controlled study, meaning that participants will be randomly assigned to receive either a patch with active drug or a matching patch which contains no drug. Participants will apply the active or placebo patch once per day for 8 weeks and, in addition, all will receive brief behavioral intervention for 8 weeks. Participants will be asked to complete assessments (questionnaires, laboratory tests, etc.) at various times in the 8-week treatment phase of the study as well as at 4 weeks and 18 weeks after completing treatment (weeks 12 and 26, respectively).

Official title: CSP #1022 - Phase 2, Double-Blind, Placebo-Controlled Trial of Selegiline Transdermal System (STS) as an Aid to Smoking Cessation.

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Detailed description: Primary Hypothesis: STS in combination with a weekly brief behavioral intervention will increase the percentage of individuals who have ceased smoking at the end of 8 weeks of treatment compared to a placebo patch control group who will receive the same behavioral intervention.

Secondary Hypothesis:

Intervention: The active treatment will be 30mg Selegiline administered through a skin patch (STS-Selegiline Transdermal System) applied every 24 hours. Patients in the placebo group will receive a matching placebo patch. Both groups will receive weekly behavioral intervention.

Primary Outcome: Smoking cessation as measured by 4 weeks of self-reproted abstinence confirmed by exhaled CO measurement during the last 4 weeks of treatment.

Study Abstract:

STUDY OBJECTIVES: The objectives of this study are to determine the safety and efficacy of selegiline transdermal system (STS) for smoking cessation in heavy smokers. It is hypothesized that the quit rate of the group of participants who receive STS in combination with behavioral intervention will be significantly greater than the quit rate of a placebo patch control group who will receive the same behavioral intervention. Quit rate is defined as the proportion of individuals who have ceased smoking at the end of 8 weeks of treatment as measured by 4-weeks of self-reported abstinence confirmed by exhaled carbon monoxide (CO) measurement during the last 4-weeks of treatment. Assessing prolonged abstinence rates at 14 and 26 weeks after the initiation of treatment, as well as the effects of treatment on withdrawal symptoms, are secondary objectives.

STUDY DESIGN: This is a double-blind, placebo-controlled, two-parallel-group study, in which 326 participants will be randomized to one of two treatment groups (123 per group). Both groups will receive 8-weeks of weekly brief behavioral intervention. The active treatment group will apply one STS (1. 0 mg/cm2 x 30 cm2) patch per day for 8 weeks. The placebo control group will apply one matched placebo control patch per day for 8-weeks. After eligibility is established, participants will be randomized to one of the two treatment groups using an adaptive randomization method, using gender, time to first cigarette after awakening (60 min or >60 min), diagnosis of depression [psychiatric evaluation by structured clinical interview (SCID)], and clinical site as variables to balance groups. Randomization and initiation of treatment will occur the same day, approximately 7 days (range 6 to 10 days) before the target quit date. Participants will be assessed for smoking status and safety measures weekly during the 8-weeks of treatment, during study week 9 (at the completion of treatment), 4-weeks after completing treatment (week 14), and finally 26 weeks after treatment initiation.

STUDY POPULATION: Two hundred forty six (246) males and females, at least 18 years of age, with a diagnosis of nicotine dependence by DSM-IV criteria, who do not have serious medical illnesses or current psychiatric disorders requiring medication, will be enrolled. To be eligible, participants must have a history of heavy cigarette use (20 cigarettes/day for the past 5 years) and provide an expired CO level 9 ppm during the two-week screening period. All women must have a negative pregnancy test on the day of treatment initiation and agree to use an acceptable method of birth control throughout the treatment period.

TREATMENTS:

STS or Matched Placebo Patch: STS (1. 0 mg/cm2 x 30 cm2) or matched placebo patch will be applied at approximately the same time daily and left in place for 24 hours each day of the 8-week treatment period.

Behavioral Intervention: During screening, the participant?s motivation to quit smoking will be assessed and a target-quit date will be selected that is 6 to 10 days post randomization and start of treatment. On the first day of treatment, each participant will be given the National Cancer Institute's Booklet entitled "Clearing the Air." Beginning during screening and continuing once per week at the weekly clinic visits, participants will be provided individual smoking cessation counseling sessions, consisting of an initial 20-minute session focusing on setting the target quit date and getting ready to quit, followed by weekly 10-minute individual counseling sessions focusing on quitting and preventing relapse.

SAFETY ASSESSMENTS: Safety will be assessed by weekly monitoring of vital signs, weight, and adverse events, and end of treatment blood chemistries, hematology, medical urinalysis, ECG, and physical exam.

EFFICACY ASSESSMENTS: The primary efficacy outcome measure will be the quit rate, defined as the proportion of participants who are abstinent during the last 4 weeks of treatment (study weeks 5 though 8), determined by self-report of smoking cessation and confirmed by expired CO < 9ppm during the last 4 weeks of measurements. Secondary outcome measures include the number of cigarettes smoked per day by participant self-report, the maximum number of consecutive days abstinent by self report, the severity of nicotine dependence using Fagerstrom Test scores, the degree of nicotine craving and the severity of nicotine withdrawal assessed using the University of Wisconsin Center for Tobacco Research and Intervention Smoking Withdrawal Scale (WSWS), prolonged abstinence (self-report of abstinence with and without confirmation by expired CO at follow-up weeks 14 and 26), and effects on mood [positive and negative affect scale (PANAS)] and severity of depression using the Hamilton Depression Rating Scale (HAM-D).

ANALYSIS: Each primary and secondary outcome variable with be analyzed using the appropriate statistical methods. It is hypothesized that STS and behavioral therapy will result in significantly higher quit rates after 8 weeks of treatment compared to placebo and behavioral therapy. All statistical tests will be two-sided at a 5% Type I error rate and a p-value < 0. 05 will determine statistical significance.

Minimum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Be greater than or equal to 18 years of age.

2. Have a DSM-IV diagnosis of nicotine dependence as determined by SCID.

3. Be currently (past 30 days) smoking equal to or greater than 20 cigarettes/day and have smoked an average of 20 equal to or greater than cigarettes/day during the past 5 years or the equivalent of 5-pack years with a pack year requiring the smoking of at least 20 cigarettes per day.

4. Be motivated to quit smoking.

5. Have an expired CO level greater than 9 ppm during screening.

6. Weigh equal to or greater than 100 lbs. (45. 4 kg).

7. Use of one of the following acceptable methods of birth control by female participants:

a. oral contraceptives

b. patch

c. barrier (diaphragm or condom)

d. intrauterine progesterone contraceptive system

e. levonorgestrel implant

f. medroxyprogesterone acetate contraceptive injection

g. surgical sterilization (medically documented hysterectomy)

h. complete abstinence from sexual intercourse

i. partner is sterile (evidence must be shown)

8. Provide written informed consent.

9. Be available for participation in the study for 28 weeks.

Exclusion Criteria:

1. Have current neurological or psychiatric disorders diagnosed by SCID that require ongoing treatment or which would make medication compliance difficult

2. Have current serious medical illnesses including, but not limited to, uncontrolled hypertension, significant heart disease (including myocardial infarction or stroke within one year of enrollment), angina, cardiovascular abnormality, severely irregular heat beat (arrhythmia), pheochromocytoma, vasoplastic diseases (e. g., Buerger's disease, Prinzmetal's angina), hyperthyroidism, diabetes requiring insulin, hepatic or renal disorders, gastroesophageal reflux disease (GERD), a peptic ulcer disease, a serious endocrine disorder, or any other unstable medical disorder that may compromise participant safety or study conduct.

3. Have a predisposition to seizures (e. g., those with a history or evidence of seizure disorder, brain tumor, cerebrovascular disease, or significant head trauma; have a family history of idiopathic seizure disorder; or are currently being treated with medications or treatment regimens which lower seizure threshold).

4. Have a history of illicit substance dependence within the past year as determined by SCID.

5. Be anticipating elective surgery within 10 weeks of signing the informed consent form that would preclude their active study participation.

6. Be anyone who in the opinion of the investigator would not be expected to complete the study protocol.

7. Have a known or suspected hypersensitivity to selegiline, any monoamine oxidase inhibitor or nicotine.

8. Have a known allergic or chronic dermatologic illness (e. g., psoriasis), that might interfere with drug absorption or which may be exacerbated by patch application.

9. Have with any allergy that requires carrying prophylactic epinephrine.

10. Be taking a medication that could interact adversely with selegiline or nicotine, with the time of administration of study agents relative to other medications based on the longest time interval of A, B, or C, below: A) Five half lives of other medication or active metabolite(s), whichever is longer B) Two weeks C) Interval recommended by other medication?s product labeling.

Medications that fall into this category include:

a. MAO inhibitors (e. g., selegiline, phenelzine, etc.) or selective serotonin reuptake inhibitors (SSRI; e. g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram) within 8 weeks of anticipated study entry.

b. Psychotropic medications, centrally active anticholinergics, anticonvulsants (case by case), antiparkinsonian agents, antidepressants, antipsychotics (including lithium carbonate), anxiolytics, psychostimulants, nootropics, cerebral enhancers, vasodilators, benzodiazepine receptor agonists, reserpine, hypnotics; including: oral neuroleptics, depot neuroleptics (10 weeks), methyldopa, ergot preparations, and tricyclic antidepressants.

c. Sympathomimetic medications: e. g., amphetamines, methylphenidate, dopamine, epinephrine, norepinephrine, levodopa, mazindol, some over-the-counter (OTC) and prescription nasal decongestants, and appetite suppressants.

d. L-tryptophan, metoclopramide.

e. Meperidine (Demerol), dextromethorphan, propoxyphene or other opiates.

f. 5-HT receptor agonists (e. g., sumitriptan succinate [Imitrex], zolmitriptan [Zomig], serotonergic agonists or antagonists (e. g. cyproheptadine [Periactin], methysergide [Sansert]).

11. Have participated in any experimental study within 4 weeks, or have taken oral selegiline or have any NRT within 2 weeks of participation.

12. Be currently using other pharmacotherapies for smoking cessation.

13. Be using tobacco produce other than cigarettes (e. g., pipes, cigars, snuff, chewing tobacco).

14. Be pregnant or lactating women.

15. Have clinically significant abnormal laboratory values in the judgment of the investigator.

16. Have had electroconvulsive therapy within the past 90 days.

University of MD, Center for Health Behavior Research (CHBR), College Park, Maryland 20742, United States
Elbert D. Glover, Ph.D., Phone: 301-405-2029, Email: eglover1@umd.edu

Robert Wood Johnson Med School, Div. of Addiction Psychiatry, Piscataway, New Jersey 08854-5635, United States
Douglas M Ziedonis, MD, Phone: 732-235-4341, Email: ziedondm@umdnj.edu

Tri-State Tobacco & Alcohol Research Center, Cincinnati, Ohio 45237, United States
Robert M Anthenelli, MD, Phone: 513-558-7194, Email: anthenrm@ucmail.uc.edu

U of Wisconin, Ctr for Tobacco Research & Intervention, Milwaukee, Wisconsin 53233, United States
Thomas Jackson, MD, Phone: 262-569-6070, Email: tj1@ctri.medicine.wisc.edu

Last updated: April 17, 2007