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

• ClinicalTrials.gov Identifier: NCT00802919
• Recruitment Status: Completed
• First Posted: December 5, 2008
• Results First Posted: December 2, 2017
• Last Update Posted: December 2, 2017
• Sponsor: Nathan Kline Institute for Psychiatric Research
• Information provided by (Responsible Party): Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia; Cigarette Smoking	Drug: Varenicline; Drug: Placebo for varenicline	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors, Independent Investigator Study
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Varenicline; Varenciline 1-2 mg/day	Drug: Varenicline; Varenicline 1-2 mg/day; Other Name: Chantix
Placebo Comparator: Matched Placebo; placebo for varenicline	Drug: Placebo for varenicline; Placebo

Outcome Measures

Primary Outcome Measures :

1. Cotinine Level [ Time Frame: Baseline, 4 weeks, 8 weeks ]
   plasma cotinine
2. Change From Baseline in Cognitive Performance [ Time Frame: basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks) ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in Psychiatric Symptoms [ Time Frame: baseline, 4 weeks, 8 weeks ]
   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.
2. Change From Basellne in Calgary Depression Scale Score [ Time Frame: baseline, 4 weeks, 8 weeks ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

Manhattan Psychatirc Center

New York, New York, United States, 10035

Nathan Kline Insitute for Psychiatric Research

Orangeburg, New York, United States, 10962

China

Peking University Institute of Mental Health

Beijing, China, 100191

Israel

The Division of Psychiatry, Chaim Sheba Medical Center

Tel Hashomer, Israel, 52621

Sponsors and Collaborators

Nathan Kline Institute for Psychiatric Research

Investigators

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

More Information

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.

• Responsible Party: Robert C. Smith MD PhD, Research Psychiatrist, Principal Investigagtor, Nathan Kline Institute for Psychiatric Research
• ClinicalTrials.gov Identifier: NCT00802919
• Other Study ID Numbers: 081/C02; FDA IND 102,411
• First Posted: December 5, 2008
• Results First Posted: December 2, 2017
• Last Update Posted: December 2, 2017
• Last Verified: October 2017

Keywords provided by Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research:

schizophrenia; smoking; nicotine; cognitive deficits; nicotinic receptors; Cognitive Deficits in Schizophrenia

Additional relevant MeSH terms:

Schizophrenia; Cognition Disorders; Cognitive Dysfunction; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurocognitive Disorders; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs