Memantine Effects on Sensorimotor Gating and Neurocognition in Schizophrenia

NCT03860597 | Completed Phase 4 Results FDA Drug

• 1 other identifier: R01MH094320
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Schizophrenia; Schizo Affective Disorder; Schizoaffective Disorder; Healthy

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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.

  7 and 14 days post baseline

Study Arms (2)

Memantine

ACTIVE COMPARATOR

Drug: Memantine

Placebo

PLACEBO COMPARATOR

Drug: Placebos

Interventions

Memantine DRUG

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.

Memantine

Placebos DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

Clinical Teaching Facility (CTF-B102) at UCSD Medical Center

San Diego, California, 92103, United States

Location

Related Publications (1)

• 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.

  PMID: 32340927 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Memantine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Neal Swerdlow, M.D., Ph.D.
• Organization: University of California, San Diego

nswerdlow@ucsd.edu

(619) 543-6270

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 4, 2019
• Study Start: April 1, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: December 21, 2022
• Results First Posted: December 21, 2022

Record last verified: 2022-12

Locations

US (1)