Trial Outcomes & Findings for Memantine Augmentation of Targeted Cognitive Training in Schizophrenia (NCT NCT04857983)

NCT ID: NCT04857983

Last Updated: 2026-05-18

Results Overview

PANSS Total Score is the primary clinical outcome measured at baseline vs. post TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS total score has a range 30-210, with higher scores indicating worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

62 participants

Primary outcome timeframe

Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Results posted on

2026-05-18

Participant Flow

Antipsychotic-medicated outpatients with a primary diagnosis of SZ or schizoaffective disorder (depressed type) ages 18-65 were recruited from the San Diego community between 7/6/2021 and 11/15/2023. Of the 62 consented/enrolled participants, 42 met inclusion criteria and were randomized to treatment, however 2 dropped out prior to initiation of treatment. Therefore 40 subjects participated in the trial.

A total of 62 participants were enrolled but 15 were excluded for not meeting inclusion criteria and 5 withdrew from the study. Two withdrew before initiation of treatment; therefore 40 participants were included. 17 were randomized to placebo and 23 were randomized to memantine.

Participant milestones

Participant milestones
Measure
TCT + PBO
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Overall Study
STARTED
17
23
Overall Study
COMPLETED
15
21
Overall Study
NOT COMPLETED
2
2

Reasons for withdrawal

Reasons for withdrawal
Measure
TCT + PBO
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Overall Study
Withdrawal by Subject
1
2
Overall Study
Positive toxicology screen
1
0

Baseline Characteristics

Memantine Augmentation of Targeted Cognitive Training in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TCT + PBO
n=17 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=23 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Total
n=40 Participants
Total of all reporting groups
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=11 Participants
2 Participants
n=9 Participants
2 Participants
n=20 Participants
Age, Continuous
48.3 years
STANDARD_DEVIATION 12.07 • n=11 Participants
48.7 years
STANDARD_DEVIATION 12.8 • n=9 Participants
48.5 years
STANDARD_DEVIATION 12.34 • n=20 Participants
Sex: Female, Male
Female
8 Participants
n=11 Participants
8 Participants
n=9 Participants
16 Participants
n=20 Participants
Sex: Female, Male
Male
9 Participants
n=11 Participants
15 Participants
n=9 Participants
24 Participants
n=20 Participants
Race (NIH/OMB)
Asian
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Race (NIH/OMB)
Black or African American
3 Participants
n=11 Participants
6 Participants
n=9 Participants
9 Participants
n=20 Participants
Race (NIH/OMB)
White
13 Participants
n=11 Participants
13 Participants
n=9 Participants
26 Participants
n=20 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=11 Participants
2 Participants
n=9 Participants
3 Participants
n=20 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=11 Participants
2 Participants
n=9 Participants
8 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
11 Participants
n=11 Participants
21 Participants
n=9 Participants
32 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Region of Enrollment
United States
17 Participants
n=11 Participants
23 Participants
n=9 Participants
40 Participants
n=20 Participants
Duration of illness
20.7 years
STANDARD_DEVIATION 11.8 • n=11 Participants
26.8 years
STANDARD_DEVIATION 13.03 • n=9 Participants
24.25 years
STANDARD_DEVIATION 12.74 • n=20 Participants

PRIMARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

PANSS Total Score is the primary clinical outcome measured at baseline vs. post TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS total score has a range 30-210, with higher scores indicating worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Positive & Negative Symptom Scale Total (PANSSt)
Post-10
52.23 score on a scale
Standard Deviation 9.74
49.29 score on a scale
Standard Deviation 12.80
Positive & Negative Symptom Scale Total (PANSSt)
Post-20
53.00 score on a scale
Standard Deviation 12.39
48.47 score on a scale
Standard Deviation 13.61
Positive & Negative Symptom Scale Total (PANSSt)
Post-30
51.54 score on a scale
Standard Deviation 11.08
46.12 score on a scale
Standard Deviation 12.30
Positive & Negative Symptom Scale Total (PANSSt)
Baseline
56.77 score on a scale
Standard Deviation 14.50
54.24 score on a scale
Standard Deviation 13.13

PRIMARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Function will be assessed via the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The World Health Organization Disability Schedule (WHODAS 2.0) has a range 12-60, with higher scores indicating worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
World Health Organization Disability Schedule (WHODAS 2.0)
Baseline
20.31 score on a scale
Standard Deviation 8.93
23.06 score on a scale
Standard Deviation 8.81
World Health Organization Disability Schedule (WHODAS 2.0)
Post-10
21.62 score on a scale
Standard Deviation 8.10
24.94 score on a scale
Standard Deviation 10.09
World Health Organization Disability Schedule (WHODAS 2.0)
Post-20
18.77 score on a scale
Standard Deviation 7.60
23.65 score on a scale
Standard Deviation 10.53
World Health Organization Disability Schedule (WHODAS 2.0)
Post-30
20.38 score on a scale
Standard Deviation 8.44
23.12 score on a scale
Standard Deviation 9.58

PRIMARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

The MCCB Global Composite T-score (MCCB-C) is the primary neurocognitive outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores (e.g., 50 indicates the population mean with a standard deviation of 10), which are standardized based on a community sample. A normal range MCCB composite T-score is between 40 and 60 and higher scores indicate better neurocognitive outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
Baseline
36.38 T-score
Standard Deviation 12.49
31.00 T-score
Standard Deviation 13.88
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
Post-10
38.46 T-score
Standard Deviation 10.72
33.76 T-score
Standard Deviation 15.54
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
Post-20
42.23 T-score
Standard Deviation 13.35
36.29 T-score
Standard Deviation 14.70
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
Post-30
40.69 T-score
Standard Deviation 14.68
36.47 T-score
Standard Deviation 15.99

SECONDARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Positive \& Negative Symptom Scale (PANSS) positive symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS positive symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the Positive Symptom subscale is 7-49 and higher scores indicate worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
Post-10
14.31 score on a scale
Standard Deviation 2.95
11.29 score on a scale
Standard Deviation 3.80
Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
Post-20
14.15 score on a scale
Standard Deviation 4.00
12.18 score on a scale
Standard Deviation 4.00
Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
Post-30
13.54 score on a scale
Standard Deviation 3.64
11.65 score on a scale
Standard Deviation 4.14
Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
Baseline
14.08 score on a scale
Standard Deviation 3.42
13.41 score on a scale
Standard Deviation 4.61

SECONDARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Positive \& Negative Symptom Scale (PANSS) negative symptom subscale measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PANSS negative symptom subscale is rated from 1 to 7 points ranging from absent to extreme. The range for the negative symptom subscale is 7-49 and higher scores indicate worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
Baseline
13.62 score on a scale
Standard Deviation 5.41
13.65 score on a scale
Standard Deviation 5.23
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
Post-10
12.07 score on a scale
Standard Deviation 3.23
12.76 score on a scale
Standard Deviation 3.77
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
Post-20
12.08 score on a scale
Standard Deviation 4.13
11.82 score on a scale
Standard Deviation 4.61
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
Post-30
11.61 score on a scale
Standard Deviation 3.50
10.76 score on a scale
Standard Deviation 3.05

SECONDARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PSYRATS auditory hallucinations subscale (AHS) consisting of 11 items, with each item being rated from 0 (absent) to 4 (severe), range 0-44, with higher scores indicating more severe auditory hallucinations or worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Psychotic Symptoms - PSYRATS Hallucination Subscale
Baseline
12.62 score on a scale
Standard Deviation 12.90
7.35 score on a scale
Standard Deviation 9.20
Psychotic Symptoms - PSYRATS Hallucination Subscale
Post-10
14.92 score on a scale
Standard Deviation 12.89
6.24 score on a scale
Standard Deviation 9.43
Psychotic Symptoms - PSYRATS Hallucination Subscale
Post-20
13.23 score on a scale
Standard Deviation 12.17
7.18 score on a scale
Standard Deviation 12.83
Psychotic Symptoms - PSYRATS Hallucination Subscale
Post-30
15.38 score on a scale
Standard Deviation 11.97
7.65 score on a scale
Standard Deviation 10.61

SECONDARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The range for the YMRS total score is 0-60, with higher scores indicating more severe manic symptoms or worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Manic Symptoms - Young Mania Rating Scale
Post-20
4.62 score on a scale
Standard Deviation 4.52
2.65 score on a scale
Standard Deviation 4.66
Manic Symptoms - Young Mania Rating Scale
Post-30
3.31 score on a scale
Standard Deviation 3.54
2.41 score on a scale
Standard Deviation 4.02
Manic Symptoms - Young Mania Rating Scale
Baseline
3.38 score on a scale
Standard Deviation 3.15
2.53 score on a scale
Standard Deviation 3.68
Manic Symptoms - Young Mania Rating Scale
Post-10
3.54 score on a scale
Standard Deviation 4.16
2.53 score on a scale
Standard Deviation 3.41

SECONDARY outcome

Timeframe: Baseline (at study enrollment), post-10 TCT sessions (approximately week 10), post-20 TCT sessions (approximately week 13) and post-30 TCT sessions (approximately week 16).

Population: 17 subjects were randomized to placebo and 23 to memantine. 3 subjects withdrew and 1 was excluded for a positive toxicology test; therefore 15 placebo and 21 memantine subjects completed the post-10 assessment. 1 placebo and 3 memantine subjects withdrew prior to the post-20 assessment. One additional memantine subject withdrew so that 13 placebo and 17 memantine subjects completed the post-30 assessment. Data tables include only those subjects who completed all assessments through post-30.

Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 16 weeks). The PHQ-9 has a range from 0 to 27 with higher scores indicating more severe depression or worse outcome.

Outcome measures

Outcome measures
Measure
TCT + PBO
n=13 Participants
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + MEM
n=17 Participants
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Current Depressive Symptoms - PHQ-9
Baseline
6.85 score on a scale
Standard Deviation 4.38
8.18 score on a scale
Standard Deviation 7.36
Current Depressive Symptoms - PHQ-9
Post-20
6.62 score on a scale
Standard Deviation 5.64
6.65 score on a scale
Standard Deviation 7.11
Current Depressive Symptoms - PHQ-9
Post-30
6.69 score on a scale
Standard Deviation 6.47
5.76 score on a scale
Standard Deviation 5.60
Current Depressive Symptoms - PHQ-9
Post-10
5.69 score on a scale
Standard Deviation 3.30
6.29 score on a scale
Standard Deviation 6.80

Adverse Events

TCT + MEM

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

TCT + PBO

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
TCT + MEM
n=23 participants at risk
Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
TCT + PBO
n=17 participants at risk
Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
Psychiatric disorders
Positive CSSRS
17.4%
4/23 • From randomization until end of follow-up, up to 13 weeks
29.4%
5/17 • From randomization until end of follow-up, up to 13 weeks
Psychiatric disorders
Positive tox
8.7%
2/23 • From randomization until end of follow-up, up to 13 weeks
41.2%
7/17 • From randomization until end of follow-up, up to 13 weeks
Cardiac disorders
High BP
4.3%
1/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Psychiatric disorders
Worsening symptoms
4.3%
1/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Gastrointestinal disorders
GI Symptoms
8.7%
2/23 • From randomization until end of follow-up, up to 13 weeks
0.00%
0/17 • From randomization until end of follow-up, up to 13 weeks
Gastrointestinal disorders
Abdominal pain
0.00%
0/23 • From randomization until end of follow-up, up to 13 weeks
11.8%
2/17 • From randomization until end of follow-up, up to 13 weeks
General disorders
Trip/fall
4.3%
1/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations
Positive COVID
0.00%
0/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations
Knee infection
0.00%
0/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Immune system disorders
Gout
0.00%
0/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks
Infections and infestations
UTI Symptoms
0.00%
0/23 • From randomization until end of follow-up, up to 13 weeks
5.9%
1/17 • From randomization until end of follow-up, up to 13 weeks

Additional Information

Gregory A. Light, Ph.D.

University of California San Diego, Department of Psychiatry

Phone: 619-316-6242

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place