Neurocognition After Perturbed Sleep (NAPS)

Neurocognition After Perturbed Sleep (NAPS)

Individuals with schizophrenia display a wide range of neurocognitive difficulties resulting in functional impairment and disability. Extensive evidence indicates insomnia and sleep disturbances play a substantial role in degrading cognitive functioning. However, the putative impact of insomnia and sleep disturbances on neurocognition and daily functioning has not been investigated in people with schizophrenia. The goal of this study is to characterize sleep in individuals with schizophrenia and quantify its impact on neurocognition and daily functioning.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Behavioral: Overnight polysomnography examinations

Detailed Description

Individuals with SZ display a broad range of neurocognitive difficulties that have been identified as major determinants of poor functioning and disability, thus representing an important public health concern and a focal target for interventions. Extensive research literatures converge in highlighting the critical role insomnia and sleep disturbances play in degrading neurocognitive functioning. Such sleep disturbances result in clinical presentations similar to neurocognitive difficulties commonly observed in people with SZ. While insomnia and sleep disturbances are highly prevalent in people with SZ, there are scant data on the impact of sleep disturbances on neurocognition in SZ, and no data quantifying their influence on daily functioning. Thus, sleep disturbances remain poorly understood and modeled in SZ, their impact is rarely considered in clinical trials, and they remain largely unaddressed by clinicians. To address this gap in knowledge, the primary aim of this study is to characterize sleep in individuals with SZ and quantify its impact on neurocognition and daily functioning. Employing an experimental, within-person, repeated assessment design, the study team will characterize sleep architecture, duration, and quality along with cognitive, electrophysiological, biomarkers and daily functioning sequelae in 40 individuals with SZ. Participants will first complete a week-long, in-home characterization of sleep duration and quality using actigraphy and a sleep diary. Next, they will complete two overnight polysomnography examinations employing two sleep schedules:

1) undisturbed sleep; and 2) restricted sleep (4 hours). As part of these assessments, participants will provide blood samples for biomarkers analyses and complete EEG-indexed memory tasks pre- and post-sleep, along with a post-sleep battery of neurocognitive functioning.

Finally, participants will complete a 3-day ambulatory assessment using actigraphy and smartphones to explore the impact of each sleep schedule on "real-world" daily functioning including symptoms, emotion regulation, and mood.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 56 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females or males age 18-60 years
• DSM-5 diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder
• Taking antipsychotic medication for >7 weeks and on current doses for 4 weeks, and/or injectable depot antipsychotics with no change in the last 3 months
• Capacity to understand all the potential risks and benefits of the study.

Exclusion Criteria:

• DSM-5 alcohol/substance diagnosis (except nicotine) within the last 6 months
• Taking medications affecting sleep propensity or architecture (other than antipsychotic medication)
• Initiation of medications known to impact cognition in previous 4 weeks or any change in doses during this period
• History of seizures/head trauma with loss of consciousness (>10 min) resulting in cognitive sequelae
• Medical or neurological conditions that could interfere with participation (e.g., untreated hypothyroidism
• Mental retardation
• Narcolepsy
• REM behavior disorder, parasomnias)
• Pregnant/ nursing
• Serious homicidal/suicidal risk (past 6 months)
• Moderate or more severe disorganization (PANSS≥4)
• Poor English reading ability (WTAR<7)
• Individuals employed as vehicle drivers/train operators or have occupations in which lapses in sustained vigilance would compromise safety
• Night shift workers or those with irregular sleep-wake rhythms (based on the week-long home actigraphy; i.e., average bedtime of 11pm±2 hours)
• Participation in the past 3 months in cognition study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Undisturbed Sleep; 8 hours sleep - Subjects randomized to the undisturbed sleep will be instructed to go to sleep at 11pm, and awoken at 7am.	Behavioral: Overnight polysomnography examinations; sleep lab for overnight polysomnography examinations
Experimental: Restricted Sleep; 4 hours sleep - Subjects randomized to the restricted sleep will be instructed to go to sleep at 3am and awoken at 7am.	Behavioral: Overnight polysomnography examinations; sleep lab for overnight polysomnography examinations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MATRICS Consensus Cognitive Battery (MCCB)	The composite score of the MATRICS Consensus Cognitive Battery (MCCB) will serve as a primary neurocognitive outcome. Neurocognitive functioning is indexed on the MCCB via T scores, with a mean of 50 and a SD of 10. Thus, higher scores indicate better neurocognitive performance, with T-scores of 70+ (i.e., 2 SD's over the mean) suggestive of exceptionally strong neurocognitive abilities.	Day 2, immediate upon wakening
MATRICS Consensus Cognitive Battery (MCCB)	The composite score of the MATRICS Consensus Cognitive Battery (MCCB) will serve as a primary neurocognitive outcome. Neurocognitive functioning is indexed on the MCCB via T scores, with a mean of 50 and a SD of 10. Thus, higher scores indicate better neurocognitive performance, with T-scores of 70+ (i.e., 2 SD's over the mean) suggestive of exceptionally strong neurocognitive abilities.	Day 16, immediate upon wakening
Polysomnography	Polysomnography will be used to characterize sleep including - latency, duration, continuity, and architecture assessed during over a night sleep.	Days 1-2 during restricted sleep and undisturbed sleep
Polysomnography	Polysomnography will be used to characterize sleep including - latency, duration, continuity, and architecture assessed during over a night sleep.	Days 15-16 during restricted sleep and undisturbed sleep

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: David Kimhy, PhD, ICAHN School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Kimhy D, Ospina L, Beck-Felts K, Fakhoury A, Mullins AE, Varga AW. The Impact of Sleep on Neurocognition and Functioning in Schizophrenia-Is It Time to Wake-Up? J Psychiatr Brain Sci. 2022;7:e220001. doi: 10.20900/jpbs.20220001. Epub 2022 Jan 25.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Sleep; Cognition; Emotion Regulation; Mood; Functioning
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia
• Other Study ID Numbers: GCO 20-1697; 1R21MH126357 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Informed Consent Form (ICF) Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. The type of analysis would be to achieve aims in the approved proposal. Data will be made available by contacting the PI via email.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No