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

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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:
Information provided by (Responsible Party):
Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Schizophrenia
Cigarette Smoking
Interventions Drug: Varenicline
Drug: Placebo for varenicline
Enrollment 93
Recruitment Details  
Pre-assignment Details Overall, 93 subjects were consented, 2 withdrew consent before randomization, and 87 provided evaluable data on at least one outcome measure. The number enrolled 93, is less than the number started 91, because 2 patients withdrew consent before randomization
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Period Title: Overall Study
Started 45 46
Completed 42 45
Not Completed 3 1
Arm/Group Title Varenicline Matched Placebo Total
Hide Arm/Group Description

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Total of all reporting groups
Overall Number of Baseline Participants 42 45 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 45 participants 87 participants
46.6  (8.9) 43.6  (10.6) 44.7  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 45 participants 87 participants
Female
7
  16.7%
6
  13.3%
13
  14.9%
Male
35
  83.3%
39
  86.7%
74
  85.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 45 participants 87 participants
white
14
  33.3%
13
  28.9%
27
  31.0%
black-AA
15
  35.7%
17
  37.8%
32
  36.8%
hispanic
5
  11.9%
7
  15.6%
12
  13.8%
chinese han
8
  19.0%
8
  17.8%
16
  18.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 42 participants 45 participants 87 participants
United States 22 27 49
China 8 8 16
Israel 12 10 22
1.Primary Outcome
Title Cotinine Level
Hide Description plasma cotinine
Time Frame Baseline, 4 weeks, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Data were available for cotinine analysis in mixed model analysis of co covariance on 34 participants in the varenicline arms and 36 participants in the placebo arm.
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description:

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Overall Number of Participants Analyzed 34 36
Mean (Standard Error)
Unit of Measure: cotinine ng/ml
baseline 257.9  (15.9) 258.6  (18.4)
week4 176.0  (16.0) 252.1  (18.7)
week8 147.0  (17.9) 264.6  (18.9)
2.Primary Outcome
Title Change From Baseline in Cognitive Performance
Hide Description 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.
Time Frame basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
N's varied from 25-32 in varenicline group and 29-35 in placebo group because all subjects did not complete all parts of MATRICS battery.Maximum number of participants is entered for number of participants because this cell entry does not allow entry of variable number of participations ( e.g. 25-32). for different scores..
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description:

Varenciline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Overall Number of Participants Analyzed 32 35
Mean (Standard Error)
Unit of Measure: T scores from MATRICS battery
MATRICS composite score diff from baseline Number Analyzed 25 participants 29 participants
-0.19  (2.14) 1.97  (1.86)
MATRICS Speed of Processing diff from baseline Number Analyzed 31 participants 35 participants
3.03  (1.52) 4.08  (1.56)
MATRICS attention-vigilance diff from baseline Number Analyzed 27 participants 29 participants
2.49  (1.99) 4.33  (1.95)
MATRICS working memory diff from baseline Number Analyzed 32 participants 35 participants
0.95  (1.82) 5.29  (1.88)
MATRICS verbal learning diff from baseline Number Analyzed 32 participants 35 participants
0.94  (1.00) 0.01  (1.04)
MATRICS visual learning diff from baseline Number Analyzed 31 participants 35 participants
4.75  (2.26) 7.85  (2.30)
MATRICS reasoning-rob sol diff from baseline Number Analyzed 32 participants 34 participants
0.38  (0.78) 2.79  (0.81)
3.Secondary Outcome
Title Change From Baseline in Psychiatric Symptoms
Hide Description 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.
Time Frame baseline, 4 weeks, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description:

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Overall Number of Participants Analyzed 39 38
Mean (Standard Error)
Unit of Measure: units on a scale
PANSS Total wk4 -baseline diff -3.56  (1.29) -0.86  (1.42)
PANSS Total wk8-baseline diff -3.05  (1.35) -0.97  (1.40)
PANSS Depression Factor wk4-basline diff -0.67  (0.24) 0.23  (0.26)
PANSS depressor factor wk8-baseline diff -0.67  (0.25) -0.10  (0.25)
4.Secondary Outcome
Title Change From Basellne in Calgary Depression Scale Score
Hide Description 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.
Time Frame baseline, 4 weeks, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Not all patients had relevant responses on Calgary Depression Scale. Data are analyzed for 36 subjects randomized to varenicline and 38 subjects randomized to placebo (total N=74).
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description:

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

Overall Number of Participants Analyzed 36 38
Mean (Standard Error)
Unit of Measure: Scores on a scale
Calgrapy Dep totl wk4-baseline diff -0.63  (0.24) -0.72  (0.27)
calgrapy dep wk8-baseline diff -0.79  (0.26) -0.88  (0.26)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Varenicline Matched Placebo
Hide Arm/Group Description

Varenicline 1-2 mg/day

Varenicline: Varenicline 1-2 mg/day

placebo for varenicline

Placebo for varenicline: Placebo

All-Cause Mortality
Varenicline Matched Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Varenicline Matched Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/45 (4.44%)      1/46 (2.17%)    
Psychiatric disorders     
psychiatric decompensation not study drug related * [1]  1/45 (2.22%)  1 0/46 (0.00%)  0
auditory hallucination not study drug related  [2]  1/45 (2.22%)  1 0/46 (0.00%)  0
verbal agression * [3]  0/45 (0.00%)  0 1/46 (2.17%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
after discharge from hospital patient decoenssated because of drug abuse and noncompliance with medication
[2]
patient developed auditory hallucinations although symptom scores had decreased on varenicline
[3]
verbal aggression lead to [psychiatric hospitalization. Patient on placebo study drug
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Varenicline Matched Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/45 (0.00%)      0/46 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Robert C. Smith MD
Organization: Nathan Kline Institute for Psychiatric Research
Phone: 845-398-6531
Other Publications:
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.
Responsible Party: Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research
ClinicalTrials.gov Identifier: NCT00802919     History of Changes
Other Study ID Numbers: 081/C02
FDA IND 102,411
First Submitted: December 4, 2008
First Posted: December 5, 2008
Results First Submitted: December 15, 2016
Results First Posted: December 2, 2017
Last Update Posted: December 2, 2017