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Trial record 29 of 3314 for:    schizophrenia

Study of the Effects of Mecamylamine and Varenicline in Schizophrenia

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ClinicalTrials.gov Identifier: NCT00455650
Recruitment Status : Completed
First Posted : April 4, 2007
Results First Posted : March 28, 2017
Last Update Posted : March 28, 2017
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
The Bowman Family Foundation
Information provided by (Responsible Party):
A. Eden Evins, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Cognition in Schizophrenia
Interventions Drug: Mecamylamine
Drug: Varenicline
Drug: Placebo
Enrollment 89
Recruitment Details Participants were stable, outpatient, non-smokers with schizophrenia on a stable dose of antipsychotic medication for at least 4 wks, from an urban community mental health clinic in Boston. Controls were recruited through media advertisements in the greater Boston area and had no lifetime history of Axis I disorders by SCID
Pre-assignment Details 89 participants were enrolled, 71 participants (30 patients, 41 controls) completed at least one medication visit and were included in the analyses. 4 participants (3 with schizophrenia, 1 control) missed one and 5 participants (3 with schizophrenia, 2 controls) missed 2 of the 3 medication visits.
Arm/Group Title Schizoph: Mecamylamine (Wk1),Varenicline (Wk2), Placebo (Wk3) Schizoph: Placebo (Wk1), Mecamylamine (Wk2), Varenicline (Wk3) Schizoph: Varenicline (Wk1), Placebo (Wk2), Mecamylamine (Wk3) Control: Mecamylamine (Wk1),Varenicline (Wk2), Placebo (Wk3) Control: Placebo (Wk1), Mecamylamine (Wk2), Varenicline (Wk3) Control: Varenicline (Wk1), Placebo (Wk2), Mecamylamine (Wk3)
Hide Arm/Group Description Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time. Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Period Title: Week 1
Started 10 10 10 14 14 13
Completed 10 10 10 14 14 13
Not Completed 0 0 0 0 0 0
Period Title: Week 2
Started 10 10 10 14 14 13
Completed 10 10 10 14 14 13
Not Completed 0 0 0 0 0 0
Period Title: Week 3
Started 10 10 10 14 14 13
Completed 10 10 10 14 14 13
Not Completed 0 0 0 0 0 0
Arm/Group Title Schizophrenia Control Total
Hide Arm/Group Description Study participants in the schizophrenia group were clinically stable, outpatient, non-smokers with schizophrenia on a stable, clinically determined dose of antipsychotic medication for at least 4 weeks, which were recruited from an urban community mental health clinic in Boston. Diagnoses were confirmed by clinical interview and medical record review Healthy volunteers were recruited through media advertisements in the greater Boston area and had no lifetime history of Axis I disorders by SCID interview and no firstdegree relatives with Axis I disorders by history Total of all reporting groups
Overall Number of Baseline Participants 30 41 71
Hide Baseline Analysis Population Description
Eighty-nine participants were enrolled, and 71 participants (30 patients, 41 controls) completed at least one medication visit and were included in the analyses. Four participants (3 with schizophrenia, 1 control) missed one and 5 participants (3 with schizophrenia, 2 controls) missed two of the three medication visits.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 41 participants 71 participants
47  (10) 37  (16) 42  (13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
Female
10
  33.3%
23
  56.1%
33
  46.5%
Male
20
  66.7%
18
  43.9%
38
  53.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
Caucasian 24 22 46
African American 5 12 17
Asian or Pacific Islander 0 4 4
Unknown 1 3 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants 41 participants 71 participants
30 41 71
1.Primary Outcome
Title Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Prolonged Attention as Assessed With the CPT-IP Hit Reaction Time Variability
Hide Description The Continuous Performance Test-Identical Pairs, CPT-IP, Version 4.0 was developed and normed for use in people with schizophrenia and normal controls. This task estimates attention by requiring an individual to push a response key when two identical pairs of shapes or numbers are presented in sequence. Stimuli were presented with increasing cognitive load: 2-, 3-, and 4-digit targets. Outcome variables measured included correct hits, hit reaction time (HRT), errors of commission: false alarms and random errors, and the primary outcome, variability, or standard deviation, of hit reaction time, HRT-SD. There is only one outcome measure time point because cognitive outcomes were analyzed using crossover analyses of covariance (ANCOVA) with drug (mecamylamine vs. varenicline vs. placebo) as a within subject factor, diagnosis (schizophrenia vs. control) as a between subject factor, as well as study period and drug administration sequence as between subject crossover design factors.
Time Frame Baseline (week 0), week 1, week 2 and week 3 as one time point (see outcome measure description)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Schizophrenia: Mecamylamine Schizophrenia: Varenicline Schizophrenia: Placebo Control: Mecamylamine Control: Varenicline Control: Placebo
Hide Arm/Group Description:
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Overall Number of Participants Analyzed 30 30 30 41 41 41
Mean (Standard Deviation)
Unit of Measure: ms
141.6  (57.5) 120.5  (58.5) 123.1  (44.9) 91.2  (31.1) 83.2  (30.2) 87.8  (21.7)
2.Secondary Outcome
Title Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Cognitive Interference as Assessed by The Three-card Stroop Task
Hide Description In the 3-card Stroop Task, 3 cards were presented; the 1st contained color names printed in black ink, the 2nd contained colored patches of ink, the 3rd contained color names printed in incongruously colored ink. Participants were asked to read or name as many items as possible in 45 seconds for each condition. Individuals are asked to identify the color of the ink of a word. They may be distracted by the presence of a word that states another color (i.e. the word “blue” written in green ink would require the answer green).The interference score was calculated by dividing the color-word score by the color score. There is only one outcome measure time point because cognitive outcomes were analyzed using crossover analyses of covariance (ANCOVA) with drug (mecamylamine vs varenicline vs pbo) as a within subject factor, diagnosis (schizophrenia vs. control) as a between subject factor as well as study period and drug administration sequence as between subject crossover design factors
Time Frame Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Schizophrenia: Mecamylamine Schizophrenia: Varenicline Schizophrenia: Placebo Control: Mecamylamine Control: Varenicline Control: Placebo
Hide Arm/Group Description:
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Overall Number of Participants Analyzed 30 30 30 41 41 41
Mean (Standard Deviation)
Unit of Measure: score
50.2  (6.8) 52.8  (8.0) 50.3  (8.3) 54.4  (10.5) 53.3  (9.2) 53.5  (8.6)
3.Secondary Outcome
Title Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Sustained Attention as Assessed by The N-back Task
Hide Description The N-back task with 1- and 2-back parametric conditions was used. During the task, a letter was displayed for 1,500 ms every 2 s with a 500 ms isi. Participants were asked to press the “1” key for letters that corresponded to the letter 1 back for the 1-back condition, the “2” key for the 2-back condition, and the “3” key for nontarget letters. Outcome variable presented is hit reaction time There is only one outcome measure time point because this outcome was analyzed using crossover analyses of covariance (ANCOVA) with drug (mecamylamine vs. varenicline vs. placebo) as a within subject factor, diagnosis (schizophrenia vs. control) as a between subject factor, as well as study period and drug administration sequence as between subject crossover design factors.
Time Frame Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Schizophrenia: Mecamylamine Schizophrenia: Varenicline Schizophrenia: Placebo Control: Mecamylamine Control: Varenicline Control: Placebo
Hide Arm/Group Description:
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Overall Number of Participants Analyzed 30 30 30 41 41 41
Mean (Standard Deviation)
Unit of Measure: ms
909.2  (250.9) 931.2  (297.9) 894.4  (282.1) 864.6  (253.9) 795.8  (241.7) 827.5  (229.3)
4.Secondary Outcome
Title Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Working Memory as Assessed by The Visual Spatial Working Memory (VSWM) Task
Hide Description In the Visual spatial working memory (VSWM), participants were asked to place the cursor where the symbol appeared immediately after its display. For 16 additional trials, participants were asked to identify the symbol location after a 30-second delay. During the delay, participants were distracted by being asked to read aloud words appearing on the screen at 2-second intervals. The outcome of interest in this task were the average distance from the target for immediate and delayed recall There is only one outcome measure time frame because this outcome was analyzed using crossover analyses of covariance (ANCOVA) with drug (mecamylamine vs. varenicline vs. placebo) as a within subject factor, diagnosis (schizophrenia vs. control) as a between subject factor, as well as study period and drug administration sequence as between subject crossover design factors.
Time Frame Baseline (week 1), week 2, week 3, week 4 analyzed as a single time point
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Schizophrenia: Mecamylamine Schizophrenia: Varenicline Schizophrenia: Placebo Control: Mecamylamine Control: Varenicline Control: Placebo
Hide Arm/Group Description:
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Mecamylamine: A single dose of 10 mg of mecamylamine (via two 5 mg capsules) is given at the start of the mecamylamine arm of the study. This is the only administration of mecamylamine given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Varenicline: A single dose of 1 mg of varenicline (via two 0.5 mg capsules) is given at the start of the varenicline arm of the study. This is the only administration of varenicline given during the course of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance.
Placebo: The placebo contains no active medication. The placebo dose is given via two capsules at the start of the placebo arm of the study. Participants' blood pressure and vitals are checked regularly for five hours after drug administration for monitoring and safety assurance. The placebo has no effects that last for any duration of time.
Overall Number of Participants Analyzed 30 30 30 41 41 41
Mean (Standard Deviation)
Unit of Measure: Distance (in)
2.83  (0.71) 2.72  (0.66) 2.87  (0.76) 2.29  (0.54) 2.28  (0.54) 2.25  (0.53)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Schizophrenia Control
Hide Arm/Group Description Study participants in the schizophrenia group were clinically stable, outpatient, non-smokers with schizophrenia on a stable, clinically determined dose of antipsychotic medication for at least 4 weeks, which were recruited from an urban community mental health clinic in Boston. Diagnoses were confirmed by clinical interview and medical record review Healthy volunteers were recruited through media advertisements in the greater Boston area and had no lifetime history of Axis I disorders by SCID interview and no firstdegree relatives with Axis I disorders by history
All-Cause Mortality
Schizophrenia Control
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Schizophrenia Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/41 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Schizophrenia Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/41 (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
Layout table for Results Point of Contact information
Name/Title: A. Eden Evins, MD, MPH
Organization: Massachusetts General Hospital
Phone: 617-643-4679
EMail: aeevins@mgh.harvard.edu
Layout table for additonal information
Responsible Party: A. Eden Evins, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00455650     History of Changes
Other Study ID Numbers: PHRC #2006-P-001361
CORRC#3-2007
First Submitted: April 2, 2007
First Posted: April 4, 2007
Results First Submitted: September 22, 2016
Results First Posted: March 28, 2017
Last Update Posted: March 28, 2017