SchizophreniaPhase 2/3NCT04857983

Memantine Augmentation of Targeted Cognitive Training in Schizophrenia

A Phase 2/3 study testing Memantine in people with Schizophrenia and Schizoaffective Disorder, run by University of California, San Diego at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Schizophrenia, Schizoaffective Disorder
What is being tested?: Memantine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 62 participants
Where: 1 siteUnited States
Study dates: 6 Jul 2021to 30 Mar 2025
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

DSM-IV diagnosis of schizophrenia or schizoaffective disorder
Written informed consent to participate in the study
Age 18-65
Absence of dementia or mental retardation
Urine toxicology negative for recreational drugs
Fluent and literate in English

Who cannot join

Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days
A history of traumatic brain injury
Auditory or visual impairments severe enough to prevent study participation
Under conservatorship (determined by Anasazi)
Pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Teaching Facility (CTF B-403 at UCSD Medical Center)
San Diego, California, 92103

Other trials in United States

About this study

Treatment of schizophrenia currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.

Read the detailed description

Treatment of schizophrenia (SZ) currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of targeted cognitive training (TCT) in schizophrenia. This project tests a rational and empirically supported platform for augmenting the benefits of TCT in antipsychotic medicated SZ patients by adjunctive daily treatment of 20 mg memantine, an FDA approved medication for the treatment of cognitive dysfunction in Alzheimer's Disease. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.

Conditions: Schizophrenia, Schizoaffective Disorder
Being tested: Memantine, Placebo
Keywords: schizophrenia, cognitive training, EEG
Medical subject headings: Schizophrenia, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MemantineDrug
Also called targeted cognitive training (TCT)
Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance
PlaceboDrug
Also called targeted cognitive training (TCT)
Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Study groups in NCT04857983
Study group	Role	What they receive
TCT + PBO	Placebo comparator	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 Receives: Drug: Placebo
TCT + MEM	Active comparator	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 Receives: Drug: Memantine

What is being measured

The primary outcome is the main question the study is designed to answer.

Positive & Negative Symptom Scale Total (PANSSt)
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.
Measured: 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).
World Health Organization Disability Schedule (WHODAS 2.0)
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.
Measured: 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).
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
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.
Measured: 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).

Secondary outcomes (5)

Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
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.
Measured: 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).
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
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.
Measured: 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).
Psychotic Symptoms - PSYRATS Hallucination Subscale
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.
Measured: 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).
Manic Symptoms - Young Mania Rating Scale
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.
Measured: 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).
Current Depressive Symptoms - PHQ-9
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.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jul 202130 Mar 2025

First posted23 Apr 2021
Study start6 Jul 2021
Primary completion30 Mar 2025
Study completion30 Mar 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of California, San DiegoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Subjects will be randomized to targeted cognitive training (TCT) and memantine (MEM) or targeted cognitive training (TCT) and placebo (PBO)
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04857983
Sponsor's protocol ID: 201502
Status last verified: Apr 2026
First submitted: 21 Apr 2021
Last updated: 18 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: There is no plan to share individual participant data with other researchers

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Memantine Augmentation of Targeted Cognitive Training in Schizophrenia
ClinicalTrials.gov ID: NCT04857983
Acronym / sponsor ID: 201502
Conditions: Schizophrenia, Schizoaffective Disorder
Keywords: schizophrenia, cognitive training, EEG
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: University of California, San DiegoUniversity, hospital or other
Study start: 6 Jul 2021 (actual)
Primary completion: 30 Mar 2025 (actual)
Study completion: 30 Mar 2025 (actual)
First posted: 23 Apr 2021 (actual)
Results: Posted 18 May 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Subjects will be randomized to targeted cognitive training (TCT) and memantine (MEM) or targeted cognitive training (TCT) and placebo (PBO)

Arm	Type	Receives
TCT + PBO	Placebo comparator	Drug: PlaceboSubjects 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	Active comparator	Drug: MemantineSubjects 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

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

DSM-IV diagnosis of schizophrenia or schizoaffective disorder
Written informed consent to participate in the study
Age 18-65
Absence of dementia or mental retardation
Urine toxicology negative for recreational drugs

Key exclusion criteria (5 listed)

Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days
A history of traumatic brain injury
Auditory or visual impairments severe enough to prevent study participation
Under conservatorship (determined by Anasazi)
Pregnancy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MemantineAlso: targeted cognitive training (TCT)Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance	Drug	TCT + MEM
PlaceboAlso: targeted cognitive training (TCT)Subjects will be assigned to take memantine or placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance	Drug	TCT + PBO

Primary outcome

Positive & Negative Symptom Scale Total (PANSSt)
Time frame: 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).
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.
World Health Organization Disability Schedule (WHODAS 2.0)
Time frame: 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).
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.
MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)
Time frame: 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).
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.

5 secondary outcomes

Positive & Negative Symptom Scale (PANSS) - Positive Symptom Subscale
Time frame: 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).
Positive & Negative Symptom Scale (PANSS) - Negative Symptom Subscale
Time frame: 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).
Psychotic Symptoms - PSYRATS Hallucination Subscale
Time frame: 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).
Manic Symptoms - Young Mania Rating Scale
Time frame: 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).
Current Depressive Symptoms - PHQ-9
Time frame: 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 and safety

Results posted to the registry on 18 May 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TCT + PBO	17	15
TCT + MEM	23	21

Primary outcome: Positive & Negative Symptom Scale Total (PANSSt)

Time frame: 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).. Mean (Standard Deviation). Unit: score on a scale

Measure	TCT + PBO n = 13	TCT + MEM n = 17
Baseline	56.77 (14.50)	54.24 (13.13)
Post-10	52.23 (9.74)	49.29 (12.80)
Post-20	53.00 (12.39)	48.47 (13.61)
Post-30	51.54 (11.08)	46.12 (12.30)

TCT + PBO vs TCT + MEM: p = 0.004, ANOVA
TCT + PBO vs TCT + MEM: p = 0.350, ANOVA
TCT + PBO vs TCT + MEM: p = 0.846, ANOVA

Population analysed: 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.

Primary outcome: World Health Organization Disability Schedule (WHODAS 2.0)

Measure	TCT + PBO n = 13	TCT + MEM n = 17
Baseline	20.31 (8.93)	23.06 (8.81)
Post-10	21.62 (8.10)	24.94 (10.09)
Post-20	18.77 (7.60)	23.65 (10.53)
Post-30	20.38 (8.44)	23.12 (9.58)

TCT + PBO vs TCT + MEM: p = 0.129, ANOVA
TCT + PBO vs TCT + MEM: p = 0.292, ANOVA
TCT + PBO vs TCT + MEM: p = 0.609, ANOVA

Primary outcome: MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C)

Measure	TCT + PBO n = 13	TCT + MEM n = 17
Baseline	36.38 (12.49)	31.00 (13.88)
Post-10	38.46 (10.72)	33.76 (15.54)
Post-20	42.23 (13.35)	36.29 (14.70)
Post-30	40.69 (14.68)	36.47 (15.99)

TCT + PBO vs TCT + MEM: p = 0.001, ANOVA
TCT + PBO vs TCT + MEM: p = 0.323, ANOVA
TCT + PBO vs TCT + MEM: p = 0.885, ANOVA

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From randomization until end of follow-up, up to 13 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TCT + PBO	0 of 17 (0%)	11 of 17 (64.7%)	0 of 17
TCT + MEM	0 of 23 (0%)	10 of 23 (43.5%)	0 of 23

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No. There is no plan to share individual participant data with other researchers

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Memantine in people with Schizophrenia and Schizoaffective Disorder, run by University of California, San Diego at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive & Negative Symptom Scale Total (PANSSt) (time frame: 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).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04857983.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026.