Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors

Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors, Independent Investigator Study

This is a 8-week double-blind placebo controlled parallel group study of the efficacy of varenicline (Chantix) for smoking cessation in schizophrenic patients, and its effect on cognitive function in patients with schizophrenia.At some sits evaluation of smoking measures is extended to 12 weeks. Correlations will be made with biological predictors of efficacy: a) measures of nicotinic receptors in lymphocytes b) DNMT1 and GAD67 mRNA in lymphocytes. Subjects will be current cigarette smokers or history of regular smokers.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Cigarette Smoking
• Intervention / Treatment: Drug: Varenicline; Drug: Placebo for varenicline

Detailed Description

This was a double-blind placebo controlled study of varenicline and matched placebo in patients with a diagnosis of schizophrenia or schizoaffective psychosis who were treated with antipsychotic medication and were cigarette smokers. Three sites (2 U.S., 1 Israel) were supported by the Stanley grant. A similar independently supported study was conducted in Beijing, China. We were allowed to access these data and combine them for our analysis of results. Subjects at each site participated in a protocol which was approved by their institutional IRB. All subjects signed informed consent.

The study evaluated multiple measures of cigarette smoking, cognitive functions by MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia), and psychiatric symptoms by PANSS (Positive and Negative Symptom Scale), SANS (Schedule For Assessment Of Negative Symptoms), and Calgary Depression scales. Lymphocytes were collected for measurement of epigenetically related mRNA's.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Institute of Mental Health
• Israel
  • Tel Hashomer, Israel, 52621
    • The Division of Psychiatry, Chaim Sheba Medical Center
• United States
  • New York
    • New York, New York, United States, 10035
      • Manhattan Psychatirc Center
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Insitute for Psychiatric Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Diagnosis of Schizophrenia or Schizoaffective Disorder Current Cigarette Smoker or History of Chronic Cigarette smoking Age 18-65 Currently taking antipsychotic medication

Exclusion Criteria:

prior history of hospitalization for acute myocardial infarction or stroke, or persistent angina pectoris with current symptoms Patients who have previously tried varenicline and have stopped taking it because of side-effects of severe nausea or vomiting suicide attempt in the last year and or have had prominent or serious suicidal thoughts in the past year Women who are pregnant, nursing, or unable to use reliable contraception significant renal impairment(Creatinine ≥ 1.5) baseline Hamilton Depression Scores is >20

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Varenicline; Varenciline 1-2 mg/day	Drug: Varenicline; Varenicline 1-2 mg/day; Other Names: Chantix
Placebo Comparator: Matched Placebo; placebo for varenicline	Drug: Placebo for varenicline; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cotinine Level	plasma cotinine	Baseline, 4 weeks, 8 weeks
Change From Baseline in Cognitive Performance	The MATRICS Consensus Cognitive Battery (MCCB)(Measurement and Treatment Research to Improve Cognition in Schizophrenia) was used to measure cognitive performance. Six Domain scores and a Composite score are calculated by the proprietary MCCB Computer Scoring Program (modified beta version) from raw scores on 10 individually administered subtests. The social cognition test was not assessed in this study. The Domain T-scores are percentile-ranked and range from <20 (<0.1 percentile) to >80 (>99.9 percentile). The Composite scores are also percentile-ranked and range from <213 (T<20, <0.1 percentile) to >487 (T>80, >99.9 percentile). Higher scores after baseline represent better outcomes. Here we report difference scores from post-treatment and baseline with positive difference scores representing better outcomes.	basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Psychiatric Symptoms	The Positive and Negative Syndrome Scale (PANSS) was used to measure psychiatric symptoms. Item scores ranged from 1 (Absent) to 6 (Severe) for symptoms on the Positive Scale (total subscale range: 7-42), the Negative Scale (total subscale range: 7-42), and the General Psychopathology Scale (total subscale range:16-96). All three subscales were summed for the PANSS total score (total scale range: 30-180). Scores closer to 30 after baseline represented better outcomes. Here we report difference scores from post-treatment and baseline with negative difference scores representing better outcomes.	baseline, 4 weeks, 8 weeks
Change From Basellne in Calgary Depression Scale Score	The Calgary Depression Scale for Schizophrenia. The scale has 9 items with ratings of 0 to 3 on each item. Total score can vary from 0 to 27. Higher scores indicate more depression. Negative change scores indicate decreasing depression.	baseline, 4 weeks, 8 weeks

Collaborators and Investigators

• Sponsor: Nathan Kline Institute for Psychiatric Research
• Investigators: Principal Investigator: Robert C. Smith, MD, PhD, Nathan Kline Institute for Psychiatric Research

Publications and helpful links

General Publications

• Smith RC, Amiaz R, Si TM, Maayan L, Jin H, Boules S, Sershen H, Li C, Ren J, Liu Y, Youseff M, Lajtha A, Guidotti A, Weiser M, Davis JM. Varenicline Effects on Smoking, Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial. PLoS One. 2016 Jan 5;11(1):e0143490. doi: 10.1371/journal.pone.0143490. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 4, 2008
• First Posted (Estimate): December 5, 2008

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: schizophrenia; smoking; nicotine; cognitive deficits; nicotinic receptors; Cognitive Deficits in Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Cognitive Dysfunction; Cognition Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 081/C02; FDA IND 102,411