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

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ClinicalTrials.gov Identifier: NCT03495024
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Stanley N. Caroff, MD, Corporal Michael J. Crescenz VA Medical Center

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:
  1. 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.
  2. 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.
  3. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
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.
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 : January 1, 2019
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : June 30, 2020


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




Primary Outcome Measures :
  1. Self-reported 7-day point prevalence of abstinence prior to week 12 [ Time Frame: 12 weeks ]
    Self-reported 7-day point prevalence of abstinence prior to week 12


Secondary Outcome Measures :
  1. A reduction in smoking was determined by a >50% reduction in mean number of cigarettes consumption per day at week 12 compared to baseline [ Time Frame: 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

  2. Abstinence determined by a CO measure cutoff of ≤ 5 ppm [ Time Frame: 12 weeks ]
    Abstinence determined by a CO measure cutoff of ≤ 5 ppm

  3. Abstinence determined by 24-hour point prevalence at week 12 [ Time Frame: 12 weeks ]
    Abstinence determined by 24-hour point prevalence at week 12


Other Outcome Measures:
  1. Percent of subjects showing Clinical Global Impression ratings of at least "much improved" [ Time Frame: 12 weeks ]
    Percent of subjects showing Clinical Global Impression ratings of at least "much improved"

  2. Percent of patients showing at least 50% improvement in AIMS score, [ Time Frame: 12 weeks ]
    Percent of patients showing at least 50% improvement in AIMS score,

  3. Mean change in the sum total of score on the AIMS (items 1-7) from the baseline to endpoint visits [ Time Frame: 12 weeks ]
    Mean change in the sum total of score on the AIMS (items 1-7) from the baseline to endpoint visits



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03495024


Contacts
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Contact: Stanley N Caroff, MD 215-823-4065 stanley.caroff@va.gov
Contact: Rosalind M Berkowitz, MD 215-823-4065 rosalind.berkowitz@va.gov

Locations
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United States, Pennsylvania
Corporal Michael J Crescenz VA Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Stanley N Caroff, MD    215-823-4065    stanley.caroff@va.gov   
Contact: Rosalind M Berkowitz, MD    215-823-4065    rosalind.berkowitz@va.gov   
Sponsors and Collaborators
Corporal Michael J. Crescenz VA Medical Center
Investigators
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Principal Investigator: Stanley N Caroff, MD Cpl. Michael J. Crescenz VA Medical Center

Publications:

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Responsible Party: Stanley N. Caroff, MD, Psychiatrist, Corporal Michael J. Crescenz VA Medical Center
ClinicalTrials.gov Identifier: NCT03495024     History of Changes
Other Study ID Numbers: 01730
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Final aggregate and pooled data analyses and results devoid of any individual identifying information will be summarized in abstract form for presentations and in a final manuscript for publication at the end of the one-year study period. Final data sets will be shared upon written request for public availability. Data sets meeting VA standards for disclosure to the public will be made available within 1 year of publication. Final data sets will be maintained locally until enterprise-level resources become available for long-term storage and access. Guidance on request and distribution processes will be provided by VA ORD. Prior to distribution, a local privacy officer will certify that the data set contains no PHI
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Within one year of publication date and maintained locally until enterprise-level resources become available for long-term storage and access by VA administration.
Access Criteria: Final data sets will be shared upon written request for public availability.Guidance on request and distribution processes will be provided by VA ORD. Prior to distribution, a local privacy officer will certify that the data set contains no PHI

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Stanley N. Caroff, MD, Corporal Michael J. Crescenz VA Medical Center:
Schizophrenia
Schizoaffective disorder
Antipsychotics
Tobacco smoking
Tardive dyskinesia
Parkinsonism

Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Dyskinesias
Parkinsonian Disorders
Tardive Dyskinesia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Dyskinesia, Drug-Induced
Antipsychotic Agents
Varenicline
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action