Ignite Creation Date:
2024-05-05 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00320697
Status:
COMPLETED
Last Update Posted:
2016-09-27
First Post:
2006-04-28
Brief Title:
Smoking Relapse Prevention in Schizophrenia
Sponsor:
North Suffolk Mental Health Association
Organization:
North Suffolk Mental Health Association
Study Overview
Official Title:
A Trial of the Effects of Bupropion Nicotine Replacement Therapy and CBT on Smoking Cessation and Smoking Relapse in Patients With Schizophrenia
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study seeks to determine if continued treatment with bupropion and nicotine replacement therapy NRT can reduce the smoking relapse rate in patients with schizophrenia
Detailed Description:
Background and Preliminary Data
Between 72 and 90 of patients with schizophrenia smoke cigarettes and schizophrenia patients are more likely than the general population to smoke and to smoke heavily 1-6 Compared with the general population patients with schizophrenia have low smoking cessation rates even through they can be both highly motivated and persistent in their attempts to quit smoking 7-10 and can tolerate short-term tobacco abstinence without significant exacerbation in clinical or cognitive symptoms 11 12 Nicotine replacement therapy NRT and bupropion are each well tolerated by patients with schizophrenia and bupropion is superior to placebo for smoking cessation in this population when added to CBT 13-20 However abstinence rates have been low 4-19 at 3-6 month follow up whereas placebo plus CBT has produced cessation rates of 0-6
It has been estimated that 45 of cigarettes sold in the US are sold to people with a mental illness 21 and that in the UK and Ireland patients with schizophrenia spend approximately one third of their weekly income on cigarettes 22 23 Age-adjusted mortality from smoking-related diseases such as pulmonary and cardiovascular disease are two to six times higher among people with schizophrenia compared to age matched samples 24-27 More effective pharmacologic treatments for smoking cessation in patients with schizophrenia are thus urgently needed
Combination treatment with bupropion and NRT has shown promise In a large study in a non-psychiatric population a combination of bupropion SR and NRT was superior to placebo and to NRT alone but not to bupropion alone for smoking cessation 28 In an open non-randomized smoking cessation study in 115 nicotine dependent patients with co-morbid psychiatric and substance use disorders patients treated with bupropion SR plus NRT and weekly CBT had significantly greater reduction in smoking than those on bupropion SR plus CBT NRT plus CBT or CBT alone 29 Subjects on a combination of bupropion SR plus NRT also had significantly greater retention in the smoking cessation program and tolerated the combination treatment well
These findings were extended to patients with schizophrenia in a 12-week randomized double-blind trial of bupropion or placebo added to NRT CBT 30 In this trial bupropion 300 mgd or identical placebo was added to NRT and CBT for 12 weeks NRT was given starting on the quit date at week 4 as nicotine patch 21 mgd for 4 weeks 14 mgd for 2 weeks and 7 mgd for 2 weeks combined with nicotine gum up to 18 mg per day prn Combination treatment with bupropion and NRT was well tolerated and more beneficial than NRT alone for significant smoking reduction in patients with schizophrenia Table 1 Figure 1 The combination treatment was also superior for continuous abstinence until week 8 when the dose of NRT was reduced When subjects were taking bupropion 300 mg per day nicotine patch 21 mg per day and prn nicotine gum up to 18 mg per day they had a cessation rate of 52 See Table 1 Patients began to relapse to smoking after the dose of nicotine patch was reduced to 14 mg per day and continued to relapse through the 12 month follow up
It is our hypothesis that the 8-12 week treatment model that has been traditionally used for smoking cessation treatment is not of adequate duration for patients with schizophrenia In our trial of bupropion combined with NRT subjects experienced a 30 relapse rate during the taper of NRT patch from 21 mgday to 7 mgday while still on bupropion In patients who are able to achieve abstinence with short-term treatment a trial of longer duration treatment with bupropion combination NRT at the dose used to quit smoking is warranted It is our hypothesis that the rate of relapse to smoking will be lower with longer duration of the pharmacologic treatment used to quit smoking Longer duration treatment can be justified in patients with schizophrenia for several reasons First schizophrenia patients have known abnormalities in nicotinic receptor expression and function and may benefit more than the general population from continued pharmacotherapy for maintenance of abstinence 32-34 Nicotinic receptors are reduced in number in patients with schizophrenia 32 35 and heavy smoking in schizophrenia may be attributable to attempts to overcome a deficit in nicotinic activity Benefits of nicotine to patients with schizophrenia include reversal of some of the specific cognitive deficits associated with schizophrenia and antipsychotic medications 36-40 Nicotine has been shown to improve learning visual and spatial working memory attention auditory sensory gating smooth pursuit eye movements and reaction time 41 42 The positive effects of chronic nicotine treatment appear to persist over time and in some studies improvements in cognition with chronic nicotine treatment become more robust over time 43 Secondly the burden of morbidity and mortality of smoking related illness is high in schizophrenia such that it warrants a harm reduction approach Continued NRT may be considered a harm reduction approach if it is associated with long term tobacco abstinence For schizophrenia patients who are heavily addicted to tobacco products and would like to try to quit smoking it may be appropriate to test whether higher abstinence rates can be sustained with longer-term treatment with bupropion and NRT combined with a behavioral intervention This study seeks to determine if continued treatment with bupropion and NRT can reduce the relapse rate in patients with schizophrenia
Study Design
We propose a study that will determine if continued treatment with bupropion and NRT can reduce smoking relapse rates in schizophrenia This study has been designed with 3 phases an initial open 8 week smoking cessation phase followed by a 44 week randomized placebo controlled relapse prevention phase and then a 3 month follow-up phase
One hundred and thirty adults with a diagnosis of schizophrenia or schizoaffective disorder will be entered into an 8-week open smoking cessation trial Subjects will receive weekly cognitive behavioral therapy CBT bupropion 300 mgd nicotine patch 21mgday and up to 20 mgday of either nicotine gum or lozenge for prn use Those who attain abstinence and agree to participate in the relapse prevention phasen60-70 will be randomized according to a double-blind parallel group design to receive continued treatment with a 21 mg nicotine patch and bupropion SR 300 mg or placebo added to CBT for 44 weeks Adverse events will be documented at each visit Study medication will be distributed bi-weekly during the double blind phase
Study Procedures
Baseline Measures and Screening
1 Review of medical chart to confirm DSMIV diagnosis of schizophreniaschizoaffective disorder and medication
2 Demographic Questionnaire
3 Clinical Rating Scales SANS Schedule for assessment of Negative symptoms BPRS Brief Psychiatric Rating Scale Hamilton Calgary depression scale AIMS Abnormal Involuntary Movement Scale SAS Simpson Angus Scale BAS Barnes Akathisia Scale Tiffany Questionnaire of Smoking Urges State-Trait Anxiety Inventory Snaith Hamilton Anhedonia scale Barrett Impulsiveness Scale SF-12 smoking Self Efficacy Questionnaire and the Wisconsin Smoking Withdrawal Scale
4 Drug alcohol and smoking history including Fagerstrom Test for Nicotine Dependence
5 Cognitive tests including AX-Continuous Performance Test WMS-III spatial span Brief visuospatial memory test Emotional Stroop finger tapping signal detection reward responsivity and WTAR IQ6 Measure of reward responsivity using a signal detection test7 Expired air CO Salivary Cotinine
8 Weight height pulse blood pressure and the UKU self-report of adverse events form
9 Salivary Drug test to exclude current abuse of PCP cannabis alcohol cocaine methamphetamine and opiates
10 Phlebotomy to measure metabolic health cotinine bupropion medication levels genes for nicotine metabolism and genes associated with smoking cessation and nicotine dependence Additional serum will be stored If there is a significant effect of continued treatment on smoking relapse this serum will be tested for comparison of lipids and inflammatory biomarkers between groups
1 Open Phase
All enrolled subjects will receive weekly CBT group sessions bupropion 300 mg daily nicotine patch 21 mgday and up to 20 mgday of nicotine gum lozenge or nasal spray for prn use Subjects will set a quit date between group sessions 3 and 4 The open phase groups will consist of 8 weekly CBT meetings with up to 10 participants Subjects who achieve 2 weeks continuous abstinence at the end of the open intervention will be eligible for the double blind relapse prevention trial
2 Relapse Prevention Phase
Subjects will be randomized to receive either nicotine patch and bupropion or placebo patch and pill added to CBT for 44 weeks Randomization will take place using a computer-generated table of random numbers
Visits will then take place bi-weekly for the first 4 visits then monthly throughout the relapse prevention phase for CBT group treatment Study medication will be distributed at each visit Smoking status will be determined at each visit with self-report and expired air CO Medication side effects will also be recorded at each visit
3 Follow- up Phase
During medication taper and after medication is discontinued subjects will attend 4 follow up visits over the next 3 months
Clinical status using rating scales will be evaluated at visits 1 11 17 20 30 and 34 Serum levels of psychiatric medications and metabolic markers will also be monitored
Subjects will be paid 5 for each of the group meetings during the open and relapse prevention phases Subjects will also be paid an additional 5 for each follow-up visit they attend for self-report and 20 for clinical and cognitive assessments Subjects who complete visits 30 and 34 at the end of the study will receive an additional 50 bonus
Subject Selection and Recruitment
Subjects are 130 adult outpatients with schizophrenia or schizoaffective disorder who smoke more than 10 cigarettes per day and wish to stop smoking Subjects will be recruited by referral from treatment staff at Freedom Trail Clinic in Boston and by self-referral by responding to posted fliers in clinic waiting rooms The Freedom Trail Clinic has established procedures for identifying and recruiting subjects for research Clinicians and members of research teams meet each week to discuss current projects Using this information clinicians approach their patients if they are likely to be suitable and interested in the study Those who contact research staff about the study will be given information by a research assistant Those who remain interested and express a desire to quit smoking will meet with a research psychiatrist At this meeting subjects will be given further information about the study including risks and benefits and screening for eligibility criteria
Case managers primary care physicians and residential treatment staff within the Boston Area will also refer subjects Research staff will meet with local case managers residential staff and primary care physicians to inform them of the study eligibility criteria and means of referral Fliers will also be placed in local mental health facilities
Between 72 and 90 of patients with schizophrenia smoke cigarettes and schizophrenia patients are more likely than the general population to smoke and to smoke heavily 1-6 Compared with the general population patients with schizophrenia have low smoking cessation rates even through they can be both highly motivated and persistent in their attempts to quit smoking 7-10 and can tolerate short-term tobacco abstinence without significant exacerbation in clinical or cognitive symptoms 11 12 Nicotine replacement therapy NRT and bupropion are each well tolerated by patients with schizophrenia and bupropion is superior to placebo for smoking cessation in this population when added to CBT 13-20 However abstinence rates have been low 4-19 at 3-6 month follow up whereas placebo plus CBT has produced cessation rates of 0-6
It has been estimated that 45 of cigarettes sold in the US are sold to people with a mental illness 21 and that in the UK and Ireland patients with schizophrenia spend approximately one third of their weekly income on cigarettes 22 23 Age-adjusted mortality from smoking-related diseases such as pulmonary and cardiovascular disease are two to six times higher among people with schizophrenia compared to age matched samples 24-27 More effective pharmacologic treatments for smoking cessation in patients with schizophrenia are thus urgently needed
Combination treatment with bupropion and NRT has shown promise In a large study in a non-psychiatric population a combination of bupropion SR and NRT was superior to placebo and to NRT alone but not to bupropion alone for smoking cessation 28 In an open non-randomized smoking cessation study in 115 nicotine dependent patients with co-morbid psychiatric and substance use disorders patients treated with bupropion SR plus NRT and weekly CBT had significantly greater reduction in smoking than those on bupropion SR plus CBT NRT plus CBT or CBT alone 29 Subjects on a combination of bupropion SR plus NRT also had significantly greater retention in the smoking cessation program and tolerated the combination treatment well
These findings were extended to patients with schizophrenia in a 12-week randomized double-blind trial of bupropion or placebo added to NRT CBT 30 In this trial bupropion 300 mgd or identical placebo was added to NRT and CBT for 12 weeks NRT was given starting on the quit date at week 4 as nicotine patch 21 mgd for 4 weeks 14 mgd for 2 weeks and 7 mgd for 2 weeks combined with nicotine gum up to 18 mg per day prn Combination treatment with bupropion and NRT was well tolerated and more beneficial than NRT alone for significant smoking reduction in patients with schizophrenia Table 1 Figure 1 The combination treatment was also superior for continuous abstinence until week 8 when the dose of NRT was reduced When subjects were taking bupropion 300 mg per day nicotine patch 21 mg per day and prn nicotine gum up to 18 mg per day they had a cessation rate of 52 See Table 1 Patients began to relapse to smoking after the dose of nicotine patch was reduced to 14 mg per day and continued to relapse through the 12 month follow up
It is our hypothesis that the 8-12 week treatment model that has been traditionally used for smoking cessation treatment is not of adequate duration for patients with schizophrenia In our trial of bupropion combined with NRT subjects experienced a 30 relapse rate during the taper of NRT patch from 21 mgday to 7 mgday while still on bupropion In patients who are able to achieve abstinence with short-term treatment a trial of longer duration treatment with bupropion combination NRT at the dose used to quit smoking is warranted It is our hypothesis that the rate of relapse to smoking will be lower with longer duration of the pharmacologic treatment used to quit smoking Longer duration treatment can be justified in patients with schizophrenia for several reasons First schizophrenia patients have known abnormalities in nicotinic receptor expression and function and may benefit more than the general population from continued pharmacotherapy for maintenance of abstinence 32-34 Nicotinic receptors are reduced in number in patients with schizophrenia 32 35 and heavy smoking in schizophrenia may be attributable to attempts to overcome a deficit in nicotinic activity Benefits of nicotine to patients with schizophrenia include reversal of some of the specific cognitive deficits associated with schizophrenia and antipsychotic medications 36-40 Nicotine has been shown to improve learning visual and spatial working memory attention auditory sensory gating smooth pursuit eye movements and reaction time 41 42 The positive effects of chronic nicotine treatment appear to persist over time and in some studies improvements in cognition with chronic nicotine treatment become more robust over time 43 Secondly the burden of morbidity and mortality of smoking related illness is high in schizophrenia such that it warrants a harm reduction approach Continued NRT may be considered a harm reduction approach if it is associated with long term tobacco abstinence For schizophrenia patients who are heavily addicted to tobacco products and would like to try to quit smoking it may be appropriate to test whether higher abstinence rates can be sustained with longer-term treatment with bupropion and NRT combined with a behavioral intervention This study seeks to determine if continued treatment with bupropion and NRT can reduce the relapse rate in patients with schizophrenia
Study Design
We propose a study that will determine if continued treatment with bupropion and NRT can reduce smoking relapse rates in schizophrenia This study has been designed with 3 phases an initial open 8 week smoking cessation phase followed by a 44 week randomized placebo controlled relapse prevention phase and then a 3 month follow-up phase
One hundred and thirty adults with a diagnosis of schizophrenia or schizoaffective disorder will be entered into an 8-week open smoking cessation trial Subjects will receive weekly cognitive behavioral therapy CBT bupropion 300 mgd nicotine patch 21mgday and up to 20 mgday of either nicotine gum or lozenge for prn use Those who attain abstinence and agree to participate in the relapse prevention phasen60-70 will be randomized according to a double-blind parallel group design to receive continued treatment with a 21 mg nicotine patch and bupropion SR 300 mg or placebo added to CBT for 44 weeks Adverse events will be documented at each visit Study medication will be distributed bi-weekly during the double blind phase
Study Procedures
Baseline Measures and Screening
1 Review of medical chart to confirm DSMIV diagnosis of schizophreniaschizoaffective disorder and medication
2 Demographic Questionnaire
3 Clinical Rating Scales SANS Schedule for assessment of Negative symptoms BPRS Brief Psychiatric Rating Scale Hamilton Calgary depression scale AIMS Abnormal Involuntary Movement Scale SAS Simpson Angus Scale BAS Barnes Akathisia Scale Tiffany Questionnaire of Smoking Urges State-Trait Anxiety Inventory Snaith Hamilton Anhedonia scale Barrett Impulsiveness Scale SF-12 smoking Self Efficacy Questionnaire and the Wisconsin Smoking Withdrawal Scale
4 Drug alcohol and smoking history including Fagerstrom Test for Nicotine Dependence
5 Cognitive tests including AX-Continuous Performance Test WMS-III spatial span Brief visuospatial memory test Emotional Stroop finger tapping signal detection reward responsivity and WTAR IQ6 Measure of reward responsivity using a signal detection test7 Expired air CO Salivary Cotinine
8 Weight height pulse blood pressure and the UKU self-report of adverse events form
9 Salivary Drug test to exclude current abuse of PCP cannabis alcohol cocaine methamphetamine and opiates
10 Phlebotomy to measure metabolic health cotinine bupropion medication levels genes for nicotine metabolism and genes associated with smoking cessation and nicotine dependence Additional serum will be stored If there is a significant effect of continued treatment on smoking relapse this serum will be tested for comparison of lipids and inflammatory biomarkers between groups
1 Open Phase
All enrolled subjects will receive weekly CBT group sessions bupropion 300 mg daily nicotine patch 21 mgday and up to 20 mgday of nicotine gum lozenge or nasal spray for prn use Subjects will set a quit date between group sessions 3 and 4 The open phase groups will consist of 8 weekly CBT meetings with up to 10 participants Subjects who achieve 2 weeks continuous abstinence at the end of the open intervention will be eligible for the double blind relapse prevention trial
2 Relapse Prevention Phase
Subjects will be randomized to receive either nicotine patch and bupropion or placebo patch and pill added to CBT for 44 weeks Randomization will take place using a computer-generated table of random numbers
Visits will then take place bi-weekly for the first 4 visits then monthly throughout the relapse prevention phase for CBT group treatment Study medication will be distributed at each visit Smoking status will be determined at each visit with self-report and expired air CO Medication side effects will also be recorded at each visit
3 Follow- up Phase
During medication taper and after medication is discontinued subjects will attend 4 follow up visits over the next 3 months
Clinical status using rating scales will be evaluated at visits 1 11 17 20 30 and 34 Serum levels of psychiatric medications and metabolic markers will also be monitored
Subjects will be paid 5 for each of the group meetings during the open and relapse prevention phases Subjects will also be paid an additional 5 for each follow-up visit they attend for self-report and 20 for clinical and cognitive assessments Subjects who complete visits 30 and 34 at the end of the study will receive an additional 50 bonus
Subject Selection and Recruitment
Subjects are 130 adult outpatients with schizophrenia or schizoaffective disorder who smoke more than 10 cigarettes per day and wish to stop smoking Subjects will be recruited by referral from treatment staff at Freedom Trail Clinic in Boston and by self-referral by responding to posted fliers in clinic waiting rooms The Freedom Trail Clinic has established procedures for identifying and recruiting subjects for research Clinicians and members of research teams meet each week to discuss current projects Using this information clinicians approach their patients if they are likely to be suitable and interested in the study Those who contact research staff about the study will be given information by a research assistant Those who remain interested and express a desire to quit smoking will meet with a research psychiatrist At this meeting subjects will be given further information about the study including risks and benefits and screening for eligibility criteria
Case managers primary care physicians and residential treatment staff within the Boston Area will also refer subjects Research staff will meet with local case managers residential staff and primary care physicians to inform them of the study eligibility criteria and means of referral Fliers will also be placed in local mental health facilities
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| HRC2005-p-001950 | None | None | None |