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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00802919
• Other study ID #: 081/C02
• Secondary ID: FDA IND 102,411
• Status: Completed
• Phase: Phase 4
• First received: December 4, 2008
• Last updated: October 24, 2017
• Start date: September 2008
• Est. completion date: December 2013

Study information

• Verified date: October 2017
• Source: Nathan Kline Institute for Psychiatric Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cigarette Smoking
• Cognition Disorders
• Cognitive Dysfunction
• Schizophrenia

Intervention

Drug:
• Varenicline
Varenicline 1-2 mg/day
• Placebo for varenicline
Placebo

Locations

Country	Name	City	State
China	Peking University Institute of Mental Health	Beijing
Israel	The Division of Psychiatry, Chaim Sheba Medical Center	Tel Hashomer
United States	Manhattan Psychatirc Center	New York	New York
United States	Nathan Kline Insitute for Psychiatric Research	Orangeburg	New York

Sponsors (1)

Lead Sponsor	Collaborator
Nathan Kline Institute for Psychiatric Research

Countries where clinical trial is conducted

United States,  China,  Israel, 

References & Publications (2)

Smith R, Amiaz, R,, Tian-Mei S, Maayan L, Jin H, Boules S, et al. (2013): Varenicline effects on smoking, cognition, and psychiatric symptoms in schizophrenia. Neuropsychopharmacology. 38:s273-s434.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cotinine Level	plasma cotinine	Baseline, 4 weeks, 8 weeks
Primary	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	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
Secondary	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