Trial Outcomes & Findings for Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia (NCT NCT03860597)

Last Updated: 2022-12-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

7 and 14 days post baseline

Results posted on

2022-12-21

Participant Flow

Participant milestones

Participant milestones
Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine Memantine: 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. Placebos: 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.	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo Memantine: 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. Placebos: 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.	Healthy Subjects: Placebo 1st, Then 20 mg Memantine Memantine: 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. Placebos: 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.	Healthy Subjects: 20 mg Memantine 1st, Then Placebo Memantine: 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. Placebos: 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.
Overall Study STARTED	11	11	10	10
Overall Study COMPLETED	11	11	10	10
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n=11 Participants Memantine: 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. Placebos: 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.	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n=11 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n=10 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n=10 Participants Memantine: 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. Placebos: 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.	Total n=42 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
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	42 Participants n=21 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
Age, Continuous	40.1 years n=5 Participants	41.0 years n=7 Participants	29.6 years n=5 Participants	29.3 years n=4 Participants	35.3 years n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	23 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	23 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: 7 and 14 days post baseline

Outcome measures

Outcome measures
Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n=9 Participants Memantine: 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. Placebos: 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.	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n=7 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n=10 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n=10 Participants Memantine: 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. Placebos: 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.
Prepulse Inhibition (PPI) Placebo	32.45 % inhibition of startle Standard Error 5.11	26.85 % inhibition of startle Standard Error 6.77	14.11 % inhibition of startle Standard Error 8.97	11.78 % inhibition of startle Standard Error 8.73
Prepulse Inhibition (PPI) Memantine	10.11 % inhibition of startle Standard Error 12.88	20.55 % inhibition of startle Standard Error 4.07	21.36 % inhibition of startle Standard Error 4.56	25.55 % inhibition of startle Standard Error 6.37

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n=11 Participants Memantine: 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. Placebos: 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.	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n=10 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n=9 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n=9 Participants Memantine: 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. Placebos: 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.
Mismatch Negativity (MMN); Unit of Measure of MMN is Microvolts. Placebo	-3.15 microvolts Standard Error 0.45	-1.60 microvolts Standard Error 0.31	-3.52 microvolts Standard Error 0.50	-3.52 microvolts Standard Error 0.50
Mismatch Negativity (MMN); Unit of Measure of MMN is Microvolts. Memantine	-2.44 microvolts Standard Error 0.54	-1.70 microvolts Standard Error 0.28	-3.28 microvolts Standard Error 0.50	-3.28 microvolts Standard Error 0.50

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine n=11 Participants Memantine: 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. Placebos: 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.	Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo n=10 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: Placebo 1st, Then 20 mg Memantine n=9 Participants Memantine: 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. Placebos: 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.	Healthy Subjects: 20 mg Memantine 1st, Then Placebo n=9 Participants Memantine: 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. Placebos: 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.
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". Placebo	0.08 Microvolts-squared Standard Error 0.02	0.07 Microvolts-squared Standard Error 0.02	0.14 Microvolts-squared Standard Error 0.03	0.14 Microvolts-squared Standard Error 0.03
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". Memantine	0.09 Microvolts-squared Standard Error 0.04	0.06 Microvolts-squared Standard Error 0.02	0.23 Microvolts-squared Standard Error 0.06	0.23 Microvolts-squared Standard Error 0.06

Adverse Events

Subjects With Schizophrenia: Placebo 1st, Then 20 mg Memantine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Subjects With Schizophrenia: 20 mg Memantine 1st, Then Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Subjects: Placebo 1st, Then 20 mg Memantine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Subjects: 20 mg Memantine 1st, Then 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

Neal Swerdlow, M.D., Ph.D.

University of California, San Diego

Phone: (619) 543-6270

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place