Trial Outcomes & Findings for Study of the Effects of Mecamylamine and Varenicline in Schizophrenia (NCT NCT00455650)
NCT ID: NCT00455650
Last Updated: 2017-03-28
Results Overview
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.
COMPLETED
NA
89 participants
Baseline (week 0), week 1, week 2 and week 3 as one time point (see outcome measure description)
2017-03-28
Participant Flow
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
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.
Participant milestones
| Measure |
Schizoph: Mecamylamine (Wk1),Varenicline (Wk2), Placebo (Wk3)
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.
|
Schizoph: Placebo (Wk1), Mecamylamine (Wk2), Varenicline (Wk3)
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.
|
Schizoph: Varenicline (Wk1), Placebo (Wk2), Mecamylamine (Wk3)
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.
|
Control: Mecamylamine (Wk1),Varenicline (Wk2), Placebo (Wk3)
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.
|
Control: Placebo (Wk1), Mecamylamine (Wk2), Varenicline (Wk3)
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.
|
Control: Varenicline (Wk1), Placebo (Wk2), Mecamylamine (Wk3)
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.
|
|---|---|---|---|---|---|---|
|
Week 1
STARTED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 1
COMPLETED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Week 2
STARTED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 2
COMPLETED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Week 3
STARTED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 3
COMPLETED
|
10
|
10
|
10
|
14
|
14
|
13
|
|
Week 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of the Effects of Mecamylamine and Varenicline in Schizophrenia
Baseline characteristics by cohort
| Measure |
Schizophrenia
n=30 Participants
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
|
Control
n=41 Participants
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
n=71 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47 years
STANDARD_DEVIATION 10 • n=5 Participants
|
37 years
STANDARD_DEVIATION 16 • n=7 Participants
|
42 years
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
24 participants
n=5 Participants
|
22 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
5 participants
n=5 Participants
|
12 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian or Pacific Islander
|
0 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
41 participants
n=7 Participants
|
71 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (week 0), week 1, week 2 and week 3 as one time point (see outcome measure 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.
Outcome measures
| Measure |
Schizophrenia: Mecamylamine
n=30 Participants
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.
|
Schizophrenia: Varenicline
n=30 Participants
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.
|
Schizophrenia: Placebo
n=30 Participants
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.
|
Control: Mecamylamine
n=41 Participants
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.
|
Control: Varenicline
n=41 Participants
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.
|
Control: Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|---|
|
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
|
141.6 ms
Standard Deviation 57.5
|
120.5 ms
Standard Deviation 58.5
|
123.1 ms
Standard Deviation 44.9
|
91.2 ms
Standard Deviation 31.1
|
83.2 ms
Standard Deviation 30.2
|
87.8 ms
Standard Deviation 21.7
|
SECONDARY outcome
Timeframe: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time pointIn 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
Outcome measures
| Measure |
Schizophrenia: Mecamylamine
n=30 Participants
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.
|
Schizophrenia: Varenicline
n=30 Participants
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.
|
Schizophrenia: Placebo
n=30 Participants
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.
|
Control: Mecamylamine
n=41 Participants
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.
|
Control: Varenicline
n=41 Participants
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.
|
Control: Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|---|
|
Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Cognitive Interference as Assessed by The Three-card Stroop Task
|
50.2 score
Standard Deviation 6.8
|
52.8 score
Standard Deviation 8.0
|
50.3 score
Standard Deviation 8.3
|
54.4 score
Standard Deviation 10.5
|
53.3 score
Standard Deviation 9.2
|
53.5 score
Standard Deviation 8.6
|
SECONDARY outcome
Timeframe: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time pointThe 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.
Outcome measures
| Measure |
Schizophrenia: Mecamylamine
n=30 Participants
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.
|
Schizophrenia: Varenicline
n=30 Participants
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.
|
Schizophrenia: Placebo
n=30 Participants
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.
|
Control: Mecamylamine
n=41 Participants
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.
|
Control: Varenicline
n=41 Participants
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.
|
Control: Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|---|
|
Effects of Mecamylamine and Varenicline Compared With Placebo in Schizophrenia and Control Groups on Sustained Attention as Assessed by The N-back Task
|
909.2 ms
Standard Deviation 250.9
|
931.2 ms
Standard Deviation 297.9
|
894.4 ms
Standard Deviation 282.1
|
864.6 ms
Standard Deviation 253.9
|
795.8 ms
Standard Deviation 241.7
|
827.5 ms
Standard Deviation 229.3
|
SECONDARY outcome
Timeframe: Baseline (week 1), week 2, week 3, week 4 analyzed as a single time pointIn 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.
Outcome measures
| Measure |
Schizophrenia: Mecamylamine
n=30 Participants
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.
|
Schizophrenia: Varenicline
n=30 Participants
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.
|
Schizophrenia: Placebo
n=30 Participants
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.
|
Control: Mecamylamine
n=41 Participants
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.
|
Control: Varenicline
n=41 Participants
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.
|
Control: Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|---|
|
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
|
2.83 Distance (in)
Standard Deviation 0.71
|
2.72 Distance (in)
Standard Deviation 0.66
|
2.87 Distance (in)
Standard Deviation 0.76
|
2.29 Distance (in)
Standard Deviation 0.54
|
2.28 Distance (in)
Standard Deviation 0.54
|
2.25 Distance (in)
Standard Deviation 0.53
|
Adverse Events
Schizophrenia
Control
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place