NAPS: Neurocognition After Perturbed Sleep

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT05032963

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

19.3

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Behavioral: Overnight polysomnography examinations	N/A

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:

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

The neurocognitive evaluators who administer the neurocognitive battery (MCCB) will be blinded to sleep schedule.

Primary Purpose:

Basic Science

Official Title:

Neurocognition After Perturbed Sleep (NAPS)

Actual Study Start Date :

Sep 21, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

MATRICS Consensus Cognitive Battery (MCCB) [Day 2, immediate upon wakening]
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.
MATRICS Consensus Cognitive Battery (MCCB) [Day 16, immediate upon wakening]
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.
Polysomnography [Days 1-2 during restricted sleep and undisturbed sleep]
Polysomnography will be used to characterize sleep including - latency, duration, continuity, and architecture assessed during over a night sleep.
Polysomnography [Days 15-16 during restricted sleep and undisturbed sleep]
Polysomnography will be used to characterize sleep including - latency, duration, continuity, and architecture assessed during over a night sleep.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Females or males age 18-50 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