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

NCT03495024 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 01730
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Tobacco Smoking; Tardive Dyskinesia; Parkinsonism

Keywords

Schizophrenia; Schizoaffective disorder; Antipsychotics; Tobacco smoking; Tardive dyskinesia; Parkinsonism

Outcome Measures

Primary Outcomes (1)

• Self-reported 7-day point prevalence of abstinence prior to week 12

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

  12 weeks

Secondary Outcomes (3)

• 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

• Abstinence determined by a CO measure cutoff of ≤ 5 ppm

  12 weeks

• Abstinence determined by 24-hour point prevalence at week 12

  12 weeks

Other Outcomes (3)

• Percent of subjects showing Clinical Global Impression ratings of at least "much improved"

  12 weeks

• Percent of patients showing at least 50% improvement in AIMS score,

  12 weeks

• Mean change in the sum total of score on the AIMS (items 1-7) from the baseline to endpoint visits

  12 weeks

Study Arms (1)

Smoking cessation with varenicline

OTHER

FDA-approved indication of varenicline for smoking cessation

Drug: Varenicline

Interventions

Varenicline DRUG

Oral medication approved to facilitate smoking cessation

Also known as: CHANTIX

Smoking cessation with varenicline

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Corporal Michael J. Crescenz VA Medical Center: lead

Study Sites (1)

Corporal Michael J Crescenz VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (7)

• Caroff SN, Campbell EC, Carroll B. Pharmacological treatment of tardive dyskinesia: recent developments. Expert Rev Neurother. 2017 Sep;17(9):871-881. doi: 10.1080/14737175.2017.1358616. Epub 2017 Jul 31.

  PMID: 28727483 BACKGROUND

• Caroff SN, Campbell EC. Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice. Psychiatr Clin North Am. 2016 Sep;39(3):391-411. doi: 10.1016/j.psc.2016.04.003. Epub 2016 Jun 23.

  PMID: 27514296 BACKGROUND

• Caroff SN, Davis VG, Miller DD, Davis SM, Rosenheck RA, McEvoy JP, Campbell EC, Saltz BL, Riggio S, Chakos MH, Swartz MS, Keefe RS, Stroup TS, Lieberman JA; CATIE Investigators. Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia. J Clin Psychiatry. 2011 Mar;72(3):295-303. doi: 10.4088/JCP.09m05793yel. Epub 2010 Aug 10.

  PMID: 20816031 BACKGROUND

• Caroff SN, Walker P, Campbell C, Lorry A, Petro C, Lynch K, Gallop R. Treatment of tardive dyskinesia with galantamine: a randomized controlled crossover trial. J Clin Psychiatry. 2007 Mar;68(3):410-5. doi: 10.4088/jcp.v68n0309.

  PMID: 17388711 BACKGROUND

• Caroff SN, Martine R, Kleiner-Fisman G, Eisa M, Lorry A, Gallop R, Stern MB, Duda JE. Treatment of levodopa-induced dyskinesias with donepezil. Parkinsonism Relat Disord. 2006 May;12(4):261-3. doi: 10.1016/j.parkreldis.2005.10.003. Epub 2005 Dec 20. No abstract available.

  PMID: 16364675 BACKGROUND

• Bordia T, Zhang D, Perez XA, Quik M. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia. Exp Neurol. 2016 Dec;286:32-39. doi: 10.1016/j.expneurol.2016.09.009. Epub 2016 Sep 19.

  PMID: 27658674 BACKGROUND

• Quik M, Bordia T, Zhang D, Perez XA. Nicotine and Nicotinic Receptor Drugs: Potential for Parkinson's Disease and Drug-Induced Movement Disorders. Int Rev Neurobiol. 2015;124:247-71. doi: 10.1016/bs.irn.2015.07.005. Epub 2015 Aug 18.

  PMID: 26472532 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Tobacco Smoking; Tardive Dyskinesia; Parkinsonian Disorders

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Smoking; Behavior; Tobacco Use; Dyskinesia, Drug-Induced; Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Basal Ganglia Diseases; Brain Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Study Officials

• Stanley N Caroff, MD

  Cpl. Michael J. Crescenz VA Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stanley N Caroff, MD

CONTACT

215-823-4065; stanley.caroff@va.gov

Rosalind M Berkowitz, MD

CONTACT

215-823-4065; rosalind.berkowitz@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Model Details: 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.

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: April 11, 2018
• Study Start: January 1, 2019
• Primary Completion: April 30, 2020
• Study Completion: June 30, 2020
• Last Updated: March 22, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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

Locations

US (1)