Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia

Healthy Clinical Trial

Official title:

Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03860597
• Other study ID #: R01MH094320
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2018
• Est. completion date: March 31, 2021

Study information

• Verified date: December 2022
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Disease
• Healthy
• Mood Disorders
• Psychotic Disorders
• Schizo Affective Disorder
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Clinical Teaching Facility (CTF-B102) at UCSD Medical Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	7 and 14 days post baseline
Primary	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.	7 and 14 days post baseline
Primary	Gamma Auditory Steady-state Response (ASSR). The Primary Unit of Measure of Auditory Steady State Response (ASSR) is Gamma Evoked Power (?EP), 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. ?EP 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.	7 and 14 days post baseline