A Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder

NCT00621777 | Completed Phase 4 Results DMC

• 2 other identifiers: PHRC# 2007-P-002221R01DA021245
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 10

Brief Summary

Varenicline (Chantix) is a smoking cessation treatment that was approved in 2006 by the FDA for treatment of nicotine dependence and may be particularly beneficial in smokers with schizophrenia or bipolar disorder. Early experience with varenicline indicates that it will be effective for smoking cessation in schizophrenia and in addition, has the potential to be therapeutic for cognitive dysfunction in this population. In addition, more data is needed to evaluate the safety, tolerability and effectiveness of Varenicline in people with bipolar disorder. To assess this possibility, we will evaluate the safety and efficacy of 12 months of varenicline in schizophrenia or bipolar disorder patients who are able to quit smoking in the short term with this treatment. To do so, we will enroll 324 smokers with schizophrenia or bipolar disorder from 6 mental health clinics in Massachusetts, New Hampshire, Michigan and Minnesota into an open, 12-week smoking cessation program that includes varenicline added to weekly group cognitive behavioral therapy (CBT). Those who achieve at least 2 weeks of continuous abstinence during the last 2 weeks of the open intervention will be randomized to the relapse prevention phase: a 40-week, double blind, placebo-controlled trial of varenicline at the dose used to quit smoking added to a tapering CBT schedule. Participants will then discontinue study medications and behavioral treatment and enter a 3-month follow up phase.

Conditions

Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Smoking

Keywords

schizophrenia; bipolar disorder; varenicline; smoking cessation; relapse prevention; cognitive behavioral therapy

Outcome Measures

Primary Outcomes (1)

• Rate of 7-day Point Prevalence Abstinence at the End of the Relapse Prevention Phase (Study Week 53) in the Extended Duration Pharmacotherapy Group vs. the Placebo Group

  76 weeks

Secondary Outcomes (2)

• Safety and Tolerability of Extended Duration Pharmacotherapy When Added to Antipsychotic Medications in Schizophrenia Patients Who Have Recently Quit Smoking as Assessed by the Brief Psychiatric Rating Scale

  at week 52

• Effect of Treatment With Varenicline Versus Placebo on Health-related Quality of Life Indices in Recently Abstinent Smokers With Schizophrenia or Bipolar Disorder as Measured by the 12-Item Short Form Health Survey (SF-12)

  at week 52

Study Arms (2)

Randomized Phase: Varenicline

ACTIVE COMPARATOR

Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Because varenicline, at a dose of 1 mg twice per day, may be a more effective treatment for sustained abstinence than bupropion, it was chosen as the medication intervention for this study.

Drug: Varenicline

Randomized Phase: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Varenicline DRUG

At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.

Also known as: Chantix

Randomized Phase: Varenicline

Placebo DRUG

At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.

Randomized Phase: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men aged 18-70
• DSM-IV diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder by diagnostic interview and chart review
• Smoke at least 10 cigarettes per day
• Clinically stable, on a stable dose of antipsychotic (schizophrenia) or mood stabilizer (bipolar) medication for at least 1 month
• No current active suicidal ideation
• Expired air carbon monoxide (CO) concentration \>9 ppm
• Willing to take study medications and set a quit date within 2-3 weeks of beginning treatment and be willing to participate in the relapse prevention and follow-up portions of the study
• Women of childbearing potential must have a negative urine pregnancy test at baseline and agree to use an approved form of contraception during the study.

You may not qualify if:

• DSM-IV diagnosis of dementia, neurodegenerative disease, or other organic mental disorder
• Substance use disorder other than nicotine or caffeine in the last 6 months
• Major depressive disorder within the last 6 months
• Serious unstable medical illness including, cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease such that hospitalization for treatment of that illness is likely within the next 2 months
• Life-threatening arrhythmia or cerebro-vascular event within 6 months, cardiovascular event within 2 months or uncontrolled hypertension
• History of multiple head injuries with neurological sequelae, a single severe head injury with lasting neurological sequelae, or current CNS tumor
• Liver function tests elevated over twice normal
• Renal insufficiency with estimated creatinine clearance \<40 ml/min
• Plan to continue use of tobacco products othe than cigarettes (e.g., cigar, pipe)
• Use of an investigational medication or device in the past 30 days
• Current suicidal or homicidal ideation

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (10)

University of Alabama Psychology Clinic

Birmingham, Alabama, 35233, United States

Location

Centerstone Research Institute

Bloomington, Indiana, 47401, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Massachusetts Mental Health Center

Boston, Massachusetts, 02115, United States

Location

Touchstone Innovare

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota Psychological Clinic

Minneapolis, Minnesota, 55454, United States

Location

West Central Behavioral Health

Claremont, New Hampshire, 03743, United States

Location

Riverbend Community Mental Health Center

Concord, New Hampshire, 03302, United States

Location

The Mental Health Center of Greater Manchester

Manchester, New Hampshire, 03103, United States

Location

Community Council of Nashua

Nashua, New Hampshire, 03063, United States

Location

Related Publications (18)

• From the Centers for Disease Control and Prevention. Annual smoking attributable mortality, years of potential life lost and economic costs--United States, 1995-1999. JAMA. 2002 May 8;287(18):2355-6. No abstract available.

  PMID: 12001942 BACKGROUND

• Addington J, el-Guebaly N, Addington D, Hodgins D. Readiness to stop smoking in schizophrenia. Can J Psychiatry. 1997 Feb;42(1):49-52. doi: 10.1177/070674379704200107.

  PMID: 9040923 BACKGROUND

• Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S, Freedman R. Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull. 1998;24(2):189-202. doi: 10.1093/oxfordjournals.schbul.a033320.

  PMID: 9613620 BACKGROUND

• Barr, R.S.; Culhane, M.A.; Pizzagalli, D.; Goff, D.C.; and Evins, A.E. A double blind placebo controlled trial of the effects of transdermal nicotine on reward responsivity in non-smokers with schizophrenia. NIMH New Clinical Drug Evaluation Unit. Boca Raton, FL, 2006

  BACKGROUND

• Breese CR, Lee MJ, Adams CE, Sullivan B, Logel J, Gillen KM, Marks MJ, Collins AC, Leonard S. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology. 2000 Oct;23(4):351-64. doi: 10.1016/S0893-133X(00)00121-4.

  PMID: 10989262 BACKGROUND

• Carroll KM, Nich C, Sifry RL, Nuro KF, Frankforter TL, Ball SA, Fenton L, Rounsaville BJ. A general system for evaluating therapist adherence and competence in psychotherapy research in the addictions. Drug Alcohol Depend. 2000 Jan 1;57(3):225-38. doi: 10.1016/s0376-8716(99)00049-6.

  PMID: 10661673 BACKGROUND

• de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry. 1995 Mar;152(3):453-5. doi: 10.1176/ajp.152.3.453.

  PMID: 7864277 BACKGROUND

• de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L. Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders. Schizophr Res. 2002 Jul 1;56(1-2):47-54. doi: 10.1016/s0920-9964(01)00217-1.

  PMID: 12084419 BACKGROUND

• Evins AE, Cather C, Rigotti NA, Freudenreich O, Henderson DC, Olm-Shipman CM, Goff DC. Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction. J Clin Psychiatry. 2004 Mar;65(3):307-11; quiz 452-3. doi: 10.4088/jcp.v65n0304.

  PMID: 15096068 BACKGROUND

• Evins AE, Cather C, Deckersbach T, Freudenreich O, Culhane MA, Olm-Shipman CM, Henderson DC, Schoenfeld DA, Goff DC, Rigotti NA. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. J Clin Psychopharmacol. 2005 Jun;25(3):218-25. doi: 10.1097/01.jcp.0000162802.54076.18.

  PMID: 15876899 BACKGROUND

• Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55. doi: 10.1001/jama.296.1.47.

  PMID: 16820546 BACKGROUND

• Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry. 1986 Aug;143(8):993-7. doi: 10.1176/ajp.143.8.993.

  PMID: 3487983 BACKGROUND

• Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. doi: 10.1001/jama.296.1.56.

  PMID: 16820547 BACKGROUND

• Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. doi: 10.1124/mol.106.025130. Epub 2006 Jun 9.

  PMID: 16766716 BACKGROUND

• Diaz FJ, James D, Botts S, Maw L, Susce MT, de Leon J. Tobacco smoking behaviors in bipolar disorder: a comparison of the general population, schizophrenia, and major depression. Bipolar Disord. 2009 Mar;11(2):154-65. doi: 10.1111/j.1399-5618.2009.00664.x.

  PMID: 19267698 BACKGROUND

• Cather C, Hoeppner S, Pachas G, Pratt S, Achtyes E, Cieslak KM, Evins AE. Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking Cessation Attempt with Varenicline and Behavioral Therapy. J Dual Diagn. 2017 Jul-Sep;13(3):168-178. doi: 10.1080/15504263.2017.1319585. Epub 2017 Apr 17.

  PMID: 28414583 DERIVED

• Thorndike AN, Achtyes ED, Cather C, Pratt S, Pachas GN, Hoeppner SS, Evins AE. Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial. J Clin Psychiatry. 2016 Mar;77(3):e320-6. doi: 10.4088/JCP.15m10074.

  PMID: 27046320 DERIVED

• Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, Achtyes ED, Ayer D, Schoenfeld DA. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014 Jan 8;311(2):145-54. doi: 10.1001/jama.2013.285113.

  PMID: 24399553 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Bipolar Disorder; Smoking; Smoking Cessation

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders; Behavior; Health Behavior

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: A. Eden Evins, MD, MPH
• Organization: Massachusetts General Hospital

a_eden_evins@hms.harvard.edu

6176434679

Study Officials

• A. Eden Evins, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A. Eden Evins, MD, MPH

Study Record Dates

• First Submitted: February 12, 2008
• First Posted: February 22, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: December 21, 2017
• Results First Posted: May 21, 2015

Record last verified: 2017-11

Locations

US (10)