SchizophreniaPhase 4NCT03860597

Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia

A Phase 4 study testing Memantine in people with Schizophrenia and Schizo Affective 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

This application seeks to determine if neurophysiological metrics of memantine (MEM)-enhanced early auditory information processing (EAIP) in schizophrenia (SZ) mediate gains in auditory processing fidelity (APF) and auditory learning. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia, Schizo Affective Disorder, Schizoaffective Disorder
What is being tested?: Memantine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 42 participants
Where: 1 siteUnited States
Study dates: 1 Apr 2018to 31 Mar 2021
Phase: Phase 4
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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

diagnosis of schizophrenia OR schizoaffective-depressed OR healthy subjects
ages 18-50 for all subjects
double barrier contraception for all subjects
not pregnant for all subjects

Who cannot join

DSM-IV Axis I or II Diagnosis for for healthy subjects
MEM or amantadine for patients
current substance abuse for all subjects
current recreational drug use for all subjects
history of other significant medical illness (e.g. cancer, diabetes, heart disease, HIV, seizures) for all subjects
open head injury or closed head injury with loss of consciousness > 1 min for all subjects

Show all 10Show fewer

hearing or visual impairment for all subjects
pregnancy for all subjects
dementia for all subjects
mental retardation for all subjects

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
San Diego, California, 92103

Other trials in United States

About this study

Conditions: Schizophrenia, Schizo Affective Disorder, Schizoaffective Disorder, Healthy
Being tested: Memantine, Placebos
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
To assess the acute effects of MEM (0 vs. 20 mg) on measures of auditory processing fidelity, auditory learning and EAIP, in AP-medicated adult SZ patients and HS.
PlacebosDrug
To assess the acute effects of MEM (0 vs. 20 mg) on measures of auditory processing fidelity, auditory learning and EAIP, in AP-medicated adult SZ patients and HS.

Study groups in NCT03860597
Study group	Role	What they receive
Memantine	Active comparator	Not described Receives: Drug: Memantine
Placebo	Placebo comparator	Not described Receives: Drug: Placebos

What is being measured

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

Prepulse Inhibition (PPI)
PPI of the startle reflex is the automatic reduction in startle magnitude (assessed by EMG of orbicularis oculi) when a startling stimulus (40 ms 118 dB(A) noise burst; "PULSE") is preceded (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. Day 1 was baseline testing: testing occurred, data was collected, but no "intervention" was given. There were two possible "interventions": active (MEM 20 mg po) and placebo. One intervention was given on day 7 post baseline, the other intervention was given on day 14 post baseline, with order of intervention balanced.
Measured: 7 and 14 days post baseline
Mismatch Negativity (MMN); Unit of Measure of MMN is Microvolts.
85 dB SPL stimuli were presented via Etymotic ER3-A insert earphones. A 4-tone auditory oddball paradigm with 82% standards \& 18% deviant stimuli, differed from standard in pitch, duration, or both. A pseudorandomized sequence produced a minimum of 3 standard tones between each deviant stimulus. All tones had 5-ms rise/fall times presented with a fixed 500-ms stimulus onset asynchrony. Subjects viewed a silent movie \& instructed to ignore auditory stimuli. EEG were continuously recorded at a sampling rate of 2048-Hz from 64 channels, using BioSemi ActiveTwo system \& downsampled to 512-Hz. Deviant-minus-standard difference waves were generated for each deviant type \& low-pass filtered (20-Hz zerophase shift, 24 dB/octave rolloff). MMN was computed as mean amplitude across 135-205 ms range for each deviant type in difference waveforms at electrode Fz. Data were analyzed by RM-ANOVA, with diagnosis as a between-subject factor, \& drug condition (placebo vs MEM) as a within-subject factor.
Measured: 7 and 14 days post baseline
Gamma Auditory Steady-state Response (ASSR). The Primary Unit of Measure of Auditory Steady State Response (ASSR) is Gamma Evoked Power (γEP), Expressed as "Microvolts-squared".
1 ms, 85 dB clicks were presented in 500 ms trains at a frequency of 40 Hz; 250 click trains were played (inter-train interval=0.5 s). EEG was continuously recorded with 64-channel BioSemi ActiveTwo system (sampling rate=2048 Hz). Data processed offline via Matlab, EEGlab, \& BrainVision Analyzer. Continuous data were segmented relative to stimulus onset (-100 ms to 500 ms) \& each epoch was baseline-corrected relative to 100 ms pre-stimulus interval. γEP was assessed based on first 100 artifact-free epochs at Fz. Averaged epochs across click trains were transformed into power spectrum via fast Fourier transform using a bin width of 2 Hz. 40 Hz power spectrum was averaged across 4 Hz band from 38-42 Hz. Data were analyzed by RM-ANOVA, with diagnosis as a between- \& drug condition (placebo vs MEM) as a within-subject factor. Analyses revealed robust \& time bin-independent effects of diagnosis \& drug across 200-500 ms window \& thus this interval was the focus of all subsequent analyses.
Measured: 7 and 14 days post baseline

Timeline

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

1 Apr 201831 Mar 2021

First posted4 Mar 2019
Study start1 Apr 2018
Primary completion31 Mar 2021
Study completion31 Mar 2021

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.
Publications (1)Papers the sponsor has linked to this study.
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 4
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03860597
Sponsor's protocol ID: R01MH094320
Status last verified: Dec 2022
First submitted: 28 Feb 2019
Last updated: 21 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Molina JL, Voytek B, Thomas ML, Joshi YB, Bhakta SG, Talledo JA, Swerdlow NR, Light GA. Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):562-568. doi: 10.1016/j.bpsc.2020.02.004. Epub 2020 Feb 22.
PubMed 32340927

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 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia
ClinicalTrials.gov ID: NCT03860597
Acronym / sponsor ID: R01MH094320
Conditions: Schizophrenia, Schizo Affective Disorder, Schizoaffective Disorder, Healthy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: University of California, San DiegoUniversity, hospital or other
Study start: 1 Apr 2018 (actual)
Primary completion: 31 Mar 2021 (actual)
Study completion: 31 Mar 2021 (actual)
First posted: 4 Mar 2019 (actual)
Results: Posted 21 Dec 2022

Clinical summary

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

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Memantine	Active comparator	Drug: Memantine
Placebo	Placebo comparator	Drug: Placebos

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

diagnosis of schizophrenia OR schizoaffective-depressed OR healthy subjects
ages 18-50 for all subjects
double barrier contraception for all subjects
not pregnant for all subjects

Key exclusion criteria (10 listed)

DSM-IV Axis I or II Diagnosis for for healthy subjects
MEM or amantadine for patients
current substance abuse for all subjects
current recreational drug use for all subjects
history of other significant medical illness (e.g. cancer, diabetes, heart disease, HIV, seizures) for all subjects

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
MemantineTo assess the acute effects of MEM (0 vs. 20 mg) on measures of auditory processing fidelity, auditory learning and EAIP, in AP-medicated adult SZ patients and HS.	Drug	Memantine
PlacebosTo assess the acute effects of MEM (0 vs. 20 mg) on measures of auditory processing fidelity, auditory learning and EAIP, in AP-medicated adult SZ patients and HS.	Drug	Placebo

Primary outcome

Prepulse Inhibition (PPI)
Time frame: 7 and 14 days post baseline
PPI of the startle reflex is the automatic reduction in startle magnitude (assessed by EMG of orbicularis oculi) when a startling stimulus (40 ms 118 dB(A) noise burst; "PULSE") is preceded (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. Day 1 was baseline testing: testing occurred, data was collected, but no "intervention" was given. There were two possible "interventions": active (MEM 20 mg po) and placebo. One intervention was given on day 7 post baseline, the other intervention was given on day 14 post baseline, with order of intervention balanced.
Mismatch Negativity (MMN); Unit of Measure of MMN is Microvolts.
Time frame: 7 and 14 days post baseline
85 dB SPL stimuli were presented via Etymotic ER3-A insert earphones. A 4-tone auditory oddball paradigm with 82% standards \& 18% deviant stimuli, differed from standard in pitch, duration, or both. A pseudorandomized sequence produced a minimum of 3 standard tones between each deviant stimulus. All tones had 5-ms rise/fall times presented with a fixed 500-ms stimulus onset asynchrony. Subjects viewed a silent movie \& instructed to ignore auditory stimuli. EEG were continuously recorded at a sampling rate of 2048-Hz from 64 channels, using BioSemi ActiveTwo system \& downsampled to 512-Hz. Deviant-minus-standard difference waves were generated for each deviant type \& low-pass filtered (20-Hz zerophase shift, 24 dB/octave rolloff). MMN was computed as mean amplitude across 135-205 ms range for each deviant type in difference waveforms at electrode Fz. Data were analyzed by RM-ANOVA, with diagnosis as a between-subject factor, \& drug condition (placebo vs MEM) as a within-subject factor.
Gamma Auditory Steady-state Response (ASSR). The Primary Unit of Measure of Auditory Steady State Response (ASSR) is Gamma Evoked Power (γEP), Expressed as "Microvolts-squared".
Time frame: 7 and 14 days post baseline
1 ms, 85 dB clicks were presented in 500 ms trains at a frequency of 40 Hz; 250 click trains were played (inter-train interval=0.5 s). EEG was continuously recorded with 64-channel BioSemi ActiveTwo system (sampling rate=2048 Hz). Data processed offline via Matlab, EEGlab, \& BrainVision Analyzer. Continuous data were segmented relative to stimulus onset (-100 ms to 500 ms) \& each epoch was baseline-corrected relative to 100 ms pre-stimulus interval. γEP was assessed based on first 100 artifact-free epochs at Fz. Averaged epochs across click trains were transformed into power spectrum via fast Fourier transform using a bin width of 2 Hz. 40 Hz power spectrum was averaged across 4 Hz band from 38-42 Hz. Data were analyzed by RM-ANOVA, with diagnosis as a between- \& drug condition (placebo vs MEM) as a within-subject factor. Analyses revealed robust \& time bin-independent effects of diagnosis \& drug across 200-500 ms window \& thus this interval was the focus of all subsequent analyses.

Results and safety

Results posted to the registry on 21 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine	11	11
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo	11	11
Healthy Subjects: Placebo 1st, Then 20 mg Memantine	10	10
Healthy Subjects: 20 mg Memantine 1st, Then Placebo	10	10

Primary outcome: Prepulse Inhibition (PPI)

Time frame: 7 and 14 days post baseline. Mean (Standard Error). Unit: % inhibition of startle

Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n = 9	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n = 7	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n = 10	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n = 10
Placebo	32.45 (5.11)	26.85 (6.77)	14.11 (8.97)	11.78 (8.73)
Memantine	10.11 (12.88)	20.55 (4.07)	21.36 (4.56)	25.55 (6.37)

Primary outcome: Mismatch Negativity (MMN); Unit of Measure of MMN is Microvolts.

Time frame: 7 and 14 days post baseline. Mean (Standard Error). Unit: microvolts

Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n = 11	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n = 10	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n = 9	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n = 9
Placebo	-3.15 (0.45)	-1.60 (0.31)	-3.52 (0.50)	-3.52 (0.50)
Memantine	-2.44 (0.54)	-1.70 (0.28)	-3.28 (0.50)	-3.28 (0.50)

Primary outcome: Gamma Auditory Steady-state Response (ASSR). The Primary Unit of Measure of Auditory Steady State Response (ASSR) is Gamma Evoked Power (γEP), Expressed as "Microvolts-squared".

Time frame: 7 and 14 days post baseline. Mean (Standard Error). Unit: Microvolts-squared

Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n = 11	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n = 10	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n = 9	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n = 9
Placebo	0.08 (0.02)	0.07 (0.02)	0.14 (0.03)	0.14 (0.03)
Memantine	0.09 (0.04)	0.06 (0.02)	0.23 (0.06)	0.23 (0.06)

Adverse events

Time frame: approximately 14 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Healthy Subjects: Placebo 1st, Then 20 mg Memantine	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Healthy Subjects: 20 mg Memantine 1st, Then Placebo	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32340927Molina JL, Voytek B, Thomas ML, Joshi YB, Bhakta SG, Talledo JA, Swerdlow NR, Light GA. Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):562-568. doi: 10.1016/j.bpsc.2020.02.004. Epub 2020 Feb 22.
Individual participant dataSharing planned: Undecided

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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 4 study testing Memantine in people with Schizophrenia and Schizo Affective 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 4 inclusion and 10 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 21 Dec 2022. 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 phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 21 Dec 2022). 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?

Prepulse Inhibition (PPI) (time frame: 7 and 14 days post baseline). 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 NCT03860597, which also lists 1 linked publication.

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 21 Dec 2022.