Trial Outcomes & Findings for Biomarker Strategies for Medication-Enhanced Cognitive Training in Schizophrenia (NCT NCT01555697)
NCT ID: NCT01555697
Last Updated: 2022-10-04
Results Overview
Prepulse inhibition of the startle reflex is the automatic reduction in startle magnitude (assessed here by EMG of orbicularis oculi) when a startling stimulus (here a 40 ms 118 dB(A) noise burst; "PULSE") is preceded (here 10 - 120 msec) by a weak stimulus (here a 20 msec burst 16 dB over background "PREPULSE"). A %PPI metric is calculated based on the relative startle magnitude on (PREPULSE + PULSE) trials vs. PULSE alone trials. Possible maximal inhibition is 100%; there is no maximal "negative" value of inhibition. There is no clear "advantage" or "disadvantage" for lower or higher %PPI values, though on average, schizophrenia patients demonstrate lower % values compared to matched healthy subjects.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
80 participants
Primary outcome timeframe
approx 45 minutes
Results posted on
2022-10-04
Participant Flow
Participant milestones
| Measure |
Subjects With Schizophrenia: Placebo 1st, Then 10 mg Memantine
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 10 mg Memantine
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 10 mg Memantine 1st, Then Placebo
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 10 mg Memantine 1st, Then Placebo
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 20 mg Memantine
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 20 mg Memantine 1st, Then Placebo
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
6 Hours Lab Testing Day 1
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
Approx 7 Day Washout
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
6 Hours Lab Testing Day 2
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Biomarker Strategies for Medication-Enhanced Cognitive Training in Schizophrenia
Baseline characteristics by cohort
| Measure |
Subjects With Schizophrenia: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
10 Participants
n=115 Participants
|
10 Participants
n=24 Participants
|
80 Participants
n=42 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Age, Continuous
|
32.4 years
n=5 Participants
|
26.4 years
n=7 Participants
|
39.2 years
n=5 Participants
|
32.0 years
n=4 Participants
|
38.9 years
n=21 Participants
|
29.6 years
n=10 Participants
|
35.7 years
n=115 Participants
|
23.8 years
n=24 Participants
|
32 years
n=42 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
3 Participants
n=24 Participants
|
22 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
7 Participants
n=24 Participants
|
58 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
5 Participants
n=24 Participants
|
18 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
5 Participants
n=24 Participants
|
61 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
1 Participants
n=24 Participants
|
3 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
3 Participants
n=24 Participants
|
16 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
2 Participants
n=24 Participants
|
14 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
3 Participants
n=24 Participants
|
38 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
2 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
10 participants
n=5 Participants
|
10 participants
n=4 Participants
|
10 participants
n=21 Participants
|
10 participants
n=10 Participants
|
10 participants
n=115 Participants
|
10 participants
n=24 Participants
|
80 participants
n=42 Participants
|
PRIMARY outcome
Timeframe: approx 45 minutesPrepulse inhibition of the startle reflex is the automatic reduction in startle magnitude (assessed here by EMG of orbicularis oculi) when a startling stimulus (here a 40 ms 118 dB(A) noise burst; "PULSE") is preceded (here 10 - 120 msec) by a weak stimulus (here a 20 msec burst 16 dB over background "PREPULSE"). A %PPI metric is calculated based on the relative startle magnitude on (PREPULSE + PULSE) trials vs. PULSE alone trials. Possible maximal inhibition is 100%; there is no maximal "negative" value of inhibition. There is no clear "advantage" or "disadvantage" for lower or higher %PPI values, though on average, schizophrenia patients demonstrate lower % values compared to matched healthy subjects.
Outcome measures
| Measure |
Subjects With Schizophrenia: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
|---|---|---|---|---|---|---|---|---|
|
Prepulse Inhibition
Placebo
|
30.4 % inhibition of startle
Standard Error 5.7
|
25.5 % inhibition of startle
Standard Error 8.1
|
23.7 % inhibition of startle
Standard Error 6.0
|
2.6 % inhibition of startle
Standard Error 19.2
|
-1.7 % inhibition of startle
Standard Error 9.9
|
-9.7 % inhibition of startle
Standard Error 33.2
|
34.2 % inhibition of startle
Standard Error 8.7
|
12.1 % inhibition of startle
Standard Error 7.3
|
|
Prepulse Inhibition
Memantine
|
28.9 % inhibition of startle
Standard Error 6.8
|
27.3 % inhibition of startle
Standard Error 6.5
|
-0.9 % inhibition of startle
Standard Error 13.7
|
31.1 % inhibition of startle
Standard Error 8.1
|
26.1 % inhibition of startle
Standard Error 7.8
|
29.9 % inhibition of startle
Standard Error 8.4
|
40.1 % inhibition of startle
Standard Error 7.1
|
14.6 % inhibition of startle
Standard Error 5.7
|
SECONDARY outcome
Timeframe: approx 1 hourMATRICS Consensus Cognitive Battery Performance: This is a standardized neurocognitive battery that assesses performance in 7 domains of neurocognition. Primary data are recorded based on normalized T-scores; a separate score is provided for each domain, and a Comprehensive score (Primary measure here) is also calculated across domains. Possible T-score range is 0 - 100; higher score reflects better performance.
Outcome measures
| Measure |
Subjects With Schizophrenia: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 10 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 10 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 10 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 10 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Healthy Subjects: Placebo 1st, Then 20 mg Memantine
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participant in this arm receive a single pill of placebo followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single 20 mg pill of memantine and is again tested in the laboratory.
|
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Schizophrenia subjects in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
Healthy Subjects: 20 mg Memantine 1st, Then Placebo
n=10 Participants
This is a crossover design with 2 active doses used as between-subject factors. Healthy participants in this arm receive a single 20 mg pill of memantine followed by about 6 hours of testing in the laboratory. One week later, that participant receives a single pill of placebo and is again tested in the laboratory.
|
|---|---|---|---|---|---|---|---|---|
|
MATRICS
Placebo
|
40.4 standardized T-score
Standard Error 3.8
|
53.4 standardized T-score
Standard Error 2.3
|
41.1 standardized T-score
Standard Error 3.8
|
56.3 standardized T-score
Standard Error 2.4
|
34.2 standardized T-score
Standard Error 4.4
|
48.6 standardized T-score
Standard Error 4.3
|
37.7 standardized T-score
Standard Error 4.6
|
66.6 standardized T-score
Standard Error 2.0
|
|
MATRICS
Memantine
|
44.6 standardized T-score
Standard Error 4.5
|
60.2 standardized T-score
Standard Error 2.7
|
34.3 standardized T-score
Standard Error 3.3
|
56.6 standardized T-score
Standard Error 6.6
|
35.8 standardized T-score
Standard Error 4.8
|
53.7 standardized T-score
Standard Error 5.8
|
31.0 standardized T-score
Standard Error 4.5
|
57.6 standardized T-score
Standard Error 1.9
|
Adverse Events
Memantine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
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