Smoking Cessation With Varenicline in Schizophrenia: Antipsychotic-Induced Neurological Symptoms as Correlates

Sponsor

Corporal Michael J. Crescenz VA Medical Center (U.S. Fed)

Overall Status

Unknown status

CT.gov ID

NCT03495024

Collaborator

(none)

Enrollment

Location

Arm

17.9

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To test the feasibility of studying effects of smoking cessation with varenicline on antipsychotic drug-induced neurological side effects, we propose a 12 week pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics. Subjects will be followed after a 2 week baseline period to assess changes in smoking status and neurological symptoms using standardized rating scales. The aim is to examine clinically significant effects on antipsychotic-induced neurological side effects that may warrant further investigation.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder Tobacco Smoking Tardive Dyskinesia Parkinsonism	Drug: Varenicline	Phase 4

Detailed Description

Objectives(s): To study whether smoking cessation with varenicline treatment will be associated with a significant reduction in symptoms of antipsychotic-induced tardive dyskinesia without worsening acute extrapyramidal symptoms.
Research Design: To test the feasibility of studying effects of smoking cessation with varenicline on antipsychotic drug-induced neurological side effects, we propose a 12 week exploratory, open-label, proof-of-concept, pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics. Subjects will be followed after a 2 week baseline period to assess changes in smoking status and neurological symptoms using standardized rating scales. The aim is to examine clinically significant effects on antipsychotic-induced neurological side effects that may warrant further investigation.
Methodology: Patients will be evaluated at a Screening Visit 1 (Week 0) and at a Baseline Visit 2 (Week 2) two weeks apart. After the Baseline Visit, subjects will be asked to cease smoking completely by the target date four weeks after the baseline visit (Week 6) and will attend a clinic Cessation Visit 4 (Week 6) for medication check and resupply. Treatment with varenicline will start at Baseline Visit 2 (Week 2) with 0.5mg hs x 3 days, 0.5mg bid x 4 days, then start 1mg bid at Visit 3 (Week 3) for the remaining 9 weeks of the study.

At the Screening and Baseline Visits, and at study visits thereafter (Visit 3-7), subjects will be evaluated for efficacy and safety, and changes in smoking or other tobacco use since the last visit. The following measures will be taken; Fagerstrom Test for Cigarette Dependence (FTCD) at screening only; Cigarette smoking will be assessed by a structured questionnaire of time-line follow-back (TLFB) usage; Expired carbon using a hand-held carbon monoxide monitor; Simpson-Angus Scale (SAS), Barnes Akathisia Scale (BAS), and the Abnormal Involuntary Movement Scale (AIMS); Global Clinical Impression Scale (CGI-S at baseline, CGI-I at final visit) for TD; C-SSRS; Brief Psychiatric Rating Scale (BPRS), Mini-Mental Status Examination (MMSE) and Hospital Anxiety and Depression Scale (HADS) at baseline and the final visit only; Brief smoking cessation counseling; Laboratory measures; Urine toxicology sample at the screening and final visits only, serum pregnancy test (women) at screening visit only; Changes in psychotropic medications; Varenicline compliance by pill counts; Adverse events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

A 12 week exploratory, open-label, proof-of-concept, pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics.A 12 week exploratory, open-label, proof-of-concept, pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Varenicline on Smoking Cessation in Patients With Schizophrenia: Evaluation of Antipsychotic Drug-Induced Neurological Symptoms as Correlates of Response

Actual Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Apr 30, 2020

Anticipated Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Smoking cessation with varenicline FDA-approved indication of varenicline for smoking cessation	Drug: Varenicline Oral medication approved to facilitate smoking cessation Other Names: CHANTIX

Arm

Intervention/Treatment

Other: Smoking cessation with varenicline

FDA-approved indication of varenicline for smoking cessation

Drug: Varenicline

Oral medication approved to facilitate smoking cessation

Other Names:

CHANTIX

Outcome Measures

Primary Outcome Measures

Self-reported 7-day point prevalence of abstinence prior to week 12 [12 weeks]
Self-reported 7-day point prevalence of abstinence prior to week 12

Secondary Outcome Measures

A reduction in smoking was determined by a >50% reduction in mean number of cigarettes consumption per day at week 12 compared to baseline [12 weeks]
A reduction in smoking was determined by a >50% reduction in mean number of cigarettes consumption per day at week 12 compared to baseline
Abstinence determined by a CO measure cutoff of ≤ 5 ppm [12 weeks]
Abstinence determined by a CO measure cutoff of ≤ 5 ppm
Abstinence determined by 24-hour point prevalence at week 12 [12 weeks]
Abstinence determined by 24-hour point prevalence at week 12

Other Outcome Measures

Percent of subjects showing Clinical Global Impression ratings of at least "much improved" [12 weeks]
Percent of subjects showing Clinical Global Impression ratings of at least "much improved"
Percent of patients showing at least 50% improvement in AIMS score, [12 weeks]
Percent of patients showing at least 50% improvement in AIMS score,
Mean change in the sum total of score on the AIMS (items 1-7) from the baseline to endpoint visits [12 weeks]
Mean change in the sum total of score on the AIMS (items 1-7) from the baseline to endpoint visits

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

DSM 5 criteria for schizophrenia or schizoaffective disorder and stable disease
Glazer-Morgenstern-Doucette criteria for TD
Smoking at least 5 cigarettes on average daily for at least 30 days prior to screening
An exhaled carbon monoxide concentration greater than 5 parts per million (ppm) at screening
Agree to stop smoking by the target date (four weeks after baseline
Concurrence for varenicline treatment from the patient's mental health provider if the patient is under mental health care; OR, if the patient is not under mental health care, the prescribing clinician should consult with a mental health provider to evaluate the patient for appropriateness to receive varenicline

Exclusion Criteria:

Have untreated or unstable acute medical or psychiatric illnesses
Have a history of seizures
History of somnambulism
Have chronic degenerative neurological illnesses (e.g., Parkinson's disease)
Have a history of active substance abuse (including marijuana abuse) in the 3 months prior to screening or a positive toxicology screen
Are receiving clozapine or cholinesterase inhibitors
Had a change in dosing or medication type of antipsychotic or anti-muscarinic for one month prior to enrollment (two months for long-acting antipsychotics)
Are unable to remain on a stable dose of antipsychotic or anti-muscarinic during the study period
Have acute suicidal ideation, intent or behavior within 12 months or risk based assessed on the C-SSRS or depression/anxiety score ≥ 8 on the HADS.
Female subjects of childbearing age will have a negative pregnancy serum test at screening and are required to use approved methods of birth control
Use of an investigational drug within 30 days of screening
Use of other smoking cessation aids (bupropion, nicotine replacement products)
Use of other tobacco products
History of allergic reactions to varenicline
Lack capacity to provide informed consent