Varenicline and Smoking Cessation in Schizophrenia (VSCS)
|Schizophrenia Smoking Cessation||Other: Sugar Pill Drug: Varenicline Drug: Bupropion HCl||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Varenicline and Smoking Cessation in Schizophrenia|
- Smoking Abstinence - Serum/Urine Measurements [ Time Frame: Week 12 ]Measured by blood/urine tests for nicotine and its break-down product cotinine.
- Smoking Abstinence - Number of Cigarettes Smoked [ Time Frame: Week 12 ]Number of cigarettes smoked at week 12 of the study by self-report.
- Smoking Abstinence - Exhaled Carbon Monoxide [ Time Frame: Week 12 ]Exhaled carbon monoxide as a biochemical verification of smoking abstinence. Values below are for week 12.
- Reduction in Smoking [ Time Frame: Week 12 ]Successful outcome will be defined as a 50% or greater reduction in self-reported cigarettes per day and a 30% greater reduction in carbon monoxide and cotinine levels. Measured at week 12
- Negative Symptoms of Schizophrenia - SANS [ Time Frame: Week 12 ]Scale for the Assessment of Negative Symptoms (SANS) a well-established test, used to assess the presence of psychosis or negative symptoms of schizophrenia. It consists of 25 questions rated on a scale of 0 (none) to 5 (severe). With a total score range of 0 to 125 points. There are 6 subscales: Affective Flattening or Blunting - (minimum, 0; maximum 35); Inappropriate Affect (minimum, 0; maximum 5); Alogia (minimum 0; maximum 25); Avolition-Apathy (minimum 0; maximum 20); Anhedonia-Asociality (minimum 0; maximum 25); Attention (minimum 0; maximum 15). Each subscale (except for Inappropriate Affect) contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 25). The global questions are included within the Total Composite score. In each case, the larger the score, the more severe the symptoms.
- Impulsivity and Inattention [ Time Frame: Week 12 ]Impulsivity and inattention will be measured using the continuous performance test. Individuals were tasked with 359 items divided six blocks (59 in block 1, 60 in blocks 2-6). Omissions result from the failure to respond to target letters. CPT% Omissions measures the percentage of responses that qualify as omissions made during the test. Higher scores indicate increased inattention. Commissions result from responses given to non-targets. CPT% Commissions measures the percentage of responses that qualify as commissions made during the test. Higher scores indicate increased inattention. Perseverations result from reaction time less than 100 ms. CPT% Perseveration % measures the percentage of responses that qualify as perseverations made during the test. The higher the score, the greater impulsivity.
- Side Effects [ Time Frame: Week 12 ]Side effects will be monitored by a physician and/or assistant and recorded (SEP). All patients withdrawn from the study because of emerging side effects will be followed until the side effects are resolved. Each item is scored based on a scale of 0=none; 1=mild; 2=moderate; and 3=severe. Below, the data are shown for participants experiencing symptoms on week 12 of the study.
- Abstinence-related Symptoms - MNWS and FTND [ Time Frame: Week 12 ]
Minnesota Nicotine Withdrawal Scale (MNWS), a patient-reported measure of nicotine withdrawal symptoms and cravings. Eight items are listed, including craving for cigarettes, irritability, frustration, or anger, anxiety, etc scored on a five point scale from 0 (normal) to 5 (severe). Patients are asked for responses for the past 24 hours and past seven days (minimum 0, maximum 32; for each subscale). The higher the score, the greater the dependence. Additionally, one question (minimum score 1, maximum score 4 measures the individual's confidence in resisting strong urges to smoke. The higher the score on this question, the greater the individual's confidence in resisting smoking urges.
The Fagerstrom Test for Nicotine Dependence measures nicotine dependence and consists of six questions with a total minimum score of 0 and a maximum score of 10. The higher the score, the greater the dependence on nicotine.
- Depression [ Time Frame: Week 12 ]Beck Depression Inventory (BDI), a self-report rating inventory measuring characteristic attitudes and symptoms of depression consisting of 21 items with each item rated on a four point scale (0=not present to 3=severe). The accepted ranges are as follows: 0 to 9 indicates no depression, 10 to 18 indicates mild to moderate depression, 19 to 29 indicates moderate to severe depression and 30 to 63 indicates severe depression.
- Abnormal Movements - BAS and SAS [ Time Frame: Week 12 ]
Barnes Akathisia Scale (BAS), a widely-used measurement of drug-induced akathisia. It consists of 4 questions with questions 1-3 scored on a scale of 0-3 with 0=normal and 3=severe (minimum score 0, maximum score 9; while item 4 is a global clinical assessment of akathisia rated on a scale of 0 (normal) to 5 (severe). The higher the score on each subsclae, the greater the severity of akathisia.
Simpson-Angus Scale (SAS), a 10-item instrument used to evaluate patients experiencing neuroleptic-induced parkinsonism and other extrapyramidal side effects. Items are rated for severity on a 0-4 scale, with 0 being normal and 4 being severe. Minimum = 0; Maximum = 40. The higher the score, the greater the severity.
- Vital Signs [ Time Frame: Week 12 ]blood pressure will be measured.
- Vital Signs - Weight [ Time Frame: Week 12 ]Weight will be measured for each participant. Values listed below are for week 12.
- Vital Signs - Pulse [ Time Frame: Week 12 ]Pulse will be measured. The values below were measured at week 12 of the study.
- Suicidality [ Time Frame: Week 12 ]The Columbia-Suicide Severity Rating Scale (C-SSRS), is a survey intended to quantify the severity of suicidal ideation and behavior. The questionaire for suicidal ideation consists of 5 questions with yes (1) /no (0) answers. If answers to questions 1 and 2 are no, questions 3-5 are skipped. Minimum of 0; Maximum of 5. The questionaire for suicidal behavior consists of seven questions rated 0 for no and 1 for yes. The minimum score is 0 and the maximum score is 7. In each case, the higher the score, the greater the severity.
- Positive Symptoms of Schizophrenia (SAPS) [ Time Frame: Week 12 ]Scale for the Assessment of Positive Symptoms (SAPS), a well-established test, used to assess the presence of psychotic symptoms of schizophrenia. There are 34 items rated on a scale of 0-5 with 0=none and 5=severe for a minimum score of 0 and a maximum score of 170. There are 4 subscales: Hallucinations (minimum score 0; maximum score 35); Delusions (minimum score 0; maximum score 65); Bizarre Behavior (minimum score 0; maximum score 25); Positive Formal Thought Disorder (minimum score 0; maximum score 45). Each subscale contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 20). The values for the Global items are included in the Total Composite score. In each case, the higher the score, the greater the severity of symptoms.
- General Psychopathology [ Time Frame: Week 12 ]Brief Psychiatric Rating Scale (BPRS), an 24-item scale measuring positive symptoms, general psychopathology, and affective symptoms commonly used for schizophrenia with each item rated on a scale of 1-7 with 1=not present and 7=severe. The minimum score is 24 and the maximum score is 168. We have used five subscales as recommended by Dingemans et al., 1995: Positive subscale (minimum score 6; maximum score 42); Negative subscale (minimum score 5; maximum score 35); Depressed subscale (minimum score 5; maximum score 35); Mania subscale (minimum score 6; maximum score 42); and Disorientation subscale (minimum score 2; maximum score 14) . For both the total score and the subscale scores, the higher the score, the greater the symptom severity. We used the BPRS version 4.0. Dingemans PMAJ, Linszen DH, Lenoir ME, Smeets RMW, 1995. Component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E). Psychopharmacology 122:263-267.
- Hit Reaction Time - CPT [ Time Frame: Week 12 ]The hit reaction time is the average speed of correct responses for the entire test given in milliseconds. The higher the score, the slower the speed. The standard error is a measure of response speed consistency. The higher the overall standard error, the greater inconsistency in the response speed. The values below were measured at week 12.
- Variability of Standard Error - CPT [ Time Frame: Week 12 ]Variability of Standard Error (VSE) is a measure of response speed consistency. VSE measures "within respondent" variability. That is, the amount of variability the individual shows in 18 separate segments of the Continuous Performance Test in relation to his or her own overall standard error. Although VSE is a different measure than Overall Standard Error, typically the two measures produce comparable results. The higher the VSE, the greater the inconsistency in the response speed. The values shown below are the VSE for Week 12.
- Detectibility (d') of Continuous Performance Test [ Time Frame: Week 12 ]The value d' is a measure of the difference between the signal (non-X) and noise (X) distributions. As such, d' provides a means for assessing an individual's discriminative power since, in general, the greater the difference between the signal and noise distributions, the better the ability to distinguish and detect X and non-X stimuli. The lower the score, the better the detectability. Values shown below are for week 12.
- Response Style Indicator (Beta) for CPT [ Time Frame: Week 12 ]Beta represents an individual's response tendency: Some individuals are cautious and choose not to respond very often. Conceptually, such individuals want to make sure they are correct when they give a response. Higher values of Beta reflect this response style. The emphasis is on avoiding commission errors. Other individuals respond more freely to make sure they respond to most or all targets, and they tend to be less concerned about mistakenly responding to a non-target. Lower values of Beta are produced by this response style. Values shown below were obtained at week 12.
- Abstinence Related Symptoms - WISDM [ Time Frame: Week 12 ]The Wisconsin Inventory of Smoking Dependence Motives (WISDM) consists of 68 items regarding smoking. Each item is rated on a scale of 1 (not true of me at all) to 7 (extremely true of me) leading to a minimum score of 68 and a maximum score of 476. The higher the score, the greater the dependence. Four of the items are grouped into a Craving subscale (minimum 4, maximum 28), the greater the score, the greater the craving. Five of the items are grouped into a Cognition subscale (minimum 5, maximum 35), the higher the score, the greater reliance on cigarette smoking for cognitive enhancement. WISDM scoring based on the original article by Piper et al., 2004. A multiple motives approach to tobacco dependence: the Wisconsin inventory of smoking dependence motives (WISDM-68). Journal of Consulting and Clinical Psychology 72:139-154.
- Urge to Smoke - MNWS [ Time Frame: Week 12 ]The Minnesota Nicotine Withdrawal Scale (MNWS) includes two items where individuals are asked to 1) declare the percentage of time they had an urge to smoke (MNWS % Urge to Smoke); and 2) declare the percentage of time they had a strong urge to smoke (MNWS % Strong Urge). For each case, percentages range from 0% to 100% - the higher the percentage, the greater urge to smoke.
- Abnormal Movements - AIMS [ Time Frame: Week 12 ]Abnormal Involuntary Movement Scale (AIMS), to assess abnormal involuntary movements associated with antipsychotic drugs. There are 10 questions, based on a five-point scale ranging from 0 (none) to 4 (severe). Items 11-14 are yes/no questions that have no impact on the score. The Total Score is the sum of questions 1-7 (minimum = 0; maximum = 28). The severity index consists of one question (item 8; rated 0=none to 4=severe) based on the rater's observation of abnormal movements The AIMS Global Score is the sum of three questions (each item rated 0=none to 4=severe) regarding abnormal movements overall (minimum score 0, maximum score 12). For the total score and subscores, the higher the score, the greater the severity of abnormal movements. Scoring is based on the chapter: Guy W (2000), Abnormal Involuntary Movement Scale (AIMS), in: Handbook of Psychiatric Measures (Rush AJ Jr, et al., eds). APA Publishing: Washington DC: pp. 166-167.
|Study Start Date:||December 2009|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Placebo Comparator: Sugar Pill
Sugar pill will be given to patients as a comparison group to the active varenicline group. In the fist week, one placebo pill will be given per patient, followed by 2 pills per day for the remaining 12 weeks of the study.
Other: Sugar Pill
Sugar pill created and masked by the pharmacy to be used as a control.
Varenicline has not previously been examined for its efficacy and safety in subjects with schizophrenia. Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study. This is an experimental group to be compared against both placebo and bupropion HCl.
Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study.
Other Name: Chantix
Active Comparator: Bupropion HCl
Bupropion HCl is an established smoking cessation agent and will be used to compare its efficacy and safety against varenicline. Subjects in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study.
Drug: Bupropion HCl
in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111149
|United States, Minnesota|
|University of Minnesota, University of Minnesota Medical Center|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||S. Hossein Fatemi, M.D., Ph.D.||University of Minnesota - Clinical and Translational Science Institute|