Wake and Sleep State Transitions on a Portable Electroencephalogram (EEG) Device in Narcolepsy Type 1 (NT1) and Healthy Participants

• ClinicalTrials.gov Identifier: NCT04445129
• Recruitment Status: Completed
• First Posted: June 24, 2020
• Last Update Posted: May 7, 2021
• Sponsor: Takeda
• Collaborator: Takeda Development Center Americas, Inc.
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to determine whether portable devices can provide measurements at home similar to those taken in the clinic, in particular in participant with NT1, and to investigate night-to-night changes in sleep patterns using these devices at home. This study may enable future at-home studies and ultimately lead to a decreased burden on the people who need these measurements.

Condition or disease	Intervention/treatment
Healthy Volunteers; Narcolepsy Type 1	Device: Portable EEG Device; Device: Portable ECG Device; Device: Accelerometry

Detailed Description:

This is a non-drug study including participants with NT1 and healthy participants using devices designed for at-home assessments. The study will assess whether a portable EEG device provides an EEG signal comparable to inpatient nPSG. The frequency and characteristics of wake and sleep patterns and transitions over multiple nights will also be characterized. Participants with NT1 who will complete the study TAK-994-1501 (NCT04096560) will be eligible to enter the current study following the appropriate washout period (60 days).

The study will enroll approximately 32 participants (16 participants with NT1 and 16 healthy participants). Participants will be enrolled in the 2 groups:

• NT1 Participants
• Healthy Participants

This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 8 days. The follow-up visit will occur on Day 10 and during this debrief, participants will answer a questionnaire on user experience (device comfort) for the wearable devices.

Study Design

• Study Type: Observational
• Actual Enrollment: 45 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Study to Assess the Frequency and Characteristics of Wake and Sleep State Transitions Over Multiple Nights in Subjects With Narcolepsy Type 1 Compared With Healthy Subjects Using a Portable Electroencephalogram Device
• Actual Study Start Date: August 3, 2020
• Actual Primary Completion Date: April 29, 2021
• Actual Study Completion Date: May 4, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Narcolepsy Type 1 Participants; Participants with NT1 on stable wake-promoting medications and exclusive of any sleep promoting medications will be fitted with the portable electrocardiogram (ECG) device combined with wrist accelerometry and undergo a 2-night nPSG combined with the portable EEG device.	Device: Portable EEG Device; Portable EEG device is lightweight and designed for nighttime wear.; Device: Portable ECG Device; Portable ECG device is waterproof and will be adhered to the chest of the participant.; Device: Accelerometry; Portable accelerometry device is noninvasive and will capture data on participant activity level, including intensity of movement, rest, and sleep.
Healthy Participants; Participants who are healthy sex- and age (plus or minus 5 years)-matched controls will be fitted with the portable ECG device combined with wrist accelerometry and undergo a 2-night nPSG combined with the portable EEG device.	Device: Portable EEG Device; Portable EEG device is lightweight and designed for nighttime wear.; Device: Portable ECG Device; Portable ECG device is waterproof and will be adhered to the chest of the participant.; Device: Accelerometry; Portable accelerometry device is noninvasive and will capture data on participant activity level, including intensity of movement, rest, and sleep.

Outcome Measures

Primary Outcome Measures :

1. Sleep State Scoring From nPSG and Portable EEG Device [ Time Frame: up to 2 Nights ]
   The concordance between EEG signals obtained from the portable EEG device with nPSG over 2 inpatient night stays will be assessed using data obtained during the inpatient setting from nPSG and a portable EEG device. Scoring of sleep stages occur in 30-seconds epoch based on American Academy of Sleep Medicine (AASM) scoring rules. The output from the nPSG and the portable EEG device will be hand scored for each participant, with the rater assigning 1 of 5 sleep/wake stages to each 30 second epoch 3 stages of non-REM (NREM) sleep (N1, N2, N3), rapid eye movement (REM), and wakefulness (W). The nPSG is a standardized procedure used to assess various sleep parameters, including sleep latency and sleep architecture. nPSG will be used to as the comparator to the portable EEG device.
2. Stage Shift Index (SSI) as Measured by Standard nPSG and EEG Device on Night 2 [ Time Frame: Night 2 ]
   SSI will be measured by standard nPSG and portable EEG device on Night 2 in the clinic. SSI will be calculated as the number of transitions between any wake or sleep stage divided by hours of total sleep time. The summary of the frequency of different stages of sleep transitions can be represented by SSI, which can be used to differentiate healthy participant from those with sleep pathology. The correlation between the SSI as measured by the portable EEG device and by the nPSG will be analyzed for participants with NT1 and healthy controls. The nPSG is a standardized procedure used to assess various sleep parameters, including sleep latency and sleep architecture. nPSG will be used as the comparator to the portable EEG device.

Secondary Outcome Measures :

1. SSI as Measured by Standard nPSG and EEG Device During the Period at Home [ Time Frame: Nights 3-7 ]
   SSI will be measured by portable EEG device on nights 3-7 at home. SSI will be calculated as the number of transitions between any wake or sleep stage divided by hours of total sleep time. The summary of the frequency of different stages of sleep transitions can be represented by SSI, which can be used to differentiate healthy participant from those with sleep pathology. The SSI will be analyzed using the intrasubject correlation (intraclass correlation across different nights) in participants with NT1 and healthy participants. The nPSG is a standardized procedure used to assess various sleep parameters, including sleep latency and sleep architecture.
2. Number of Microsleeps and State Transitions During the Maintenance of Wakefulness Tests (MWTs) [ Time Frame: Day 2 ]
   Micro sleeps are defined as appearance of any stage of sleep arising out of wakefulness lasting from 3 seconds to less than or equal to (<=) 15 seconds and assessed on signals obtained from portable EEG device. State transition refers to switch between wake and sleep. MWT is a validated, objective measure used to measure excessive daytime somnolence (EDS) in clinical studies. MWT evaluate a person's ability to remain awake under soporific conditions for a defined period. Wakefulness will be measured indirectly by time to fall asleep using MWT. Four 40-minute trials will be administered (each 4 session 40-minute MWT is considered as complete test). Sleep onset is defined as first epoch of greater than 15 seconds of cumulative sleep in a 30-second epoch. Trials are ended after 40 minutes if no sleep occurs/after unequivocal sleep, defined as 3 consecutive epochs of stage 1 sleep or 1 epoch of any other stage of sleep. If no sleep has been observed, then latency is defined as 40 minutes.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Healthy Participants, who maintain a consistent sleep-wake cycle and participants with NT1.

Criteria

Inclusion Criteria:

1. Has access to at-home Wi-Fi and can add an internet-ready device with assistance.
2. Body mass index (BMI) between greater than equal to (>=) 18.0 and less than or equal to (<=) 40.0 kilogram per square meter (kg/m^2) at the screening visit.
3. Must have regular sleep-wake habits (example, routinely spending 6.5 to 8.5 hours sleeping nightly, not oversleeping by more than 2 hours on weekends, that is, total sleep not more than approximately 10.5 hours) as determined by investigator interviews and confirmed in accelerometry/actigraphy records obtained between screening and first visit (measured using a minimum of 10 day/night consecutive periods) and who regularly fall asleep between 9:30 PM and 12:00 AM (healthy participants only).
4. Must not require use of sleep aids or must be willing to discontinue use of sleep aids for the duration of the study.
5. Has completed the TAK-994-1501 study, the participant is eligible to enter the current study following the appropriate washout period (60 days).

Participants With NT1 Only:

1. With NT1 who is drug-naïve may also be enrolled.
2. With NT1 must present with subjective sleep complaint.
3. With NT1 must have a diagnosis of NT1, as defined by the International Classification of Sleep Disorders, 3rd edition (ICSD-3) criteria.

Exclusion Criteria:

1. Has a current diagnosis of cancer except for squamous or basal cell skin cancer.
2. Has a nicotine or marijuana dependence that is likely to have an effect on sleep (example, a participant who routinely awakens at night to smoke) and/or an unwillingness to discontinue all smoking and nicotine use during the confinement portions of the study.
3. Cannot maintain stable sleep environment at home, for example, due to young children not yet sleeping through the night or partners with disrupted sleep (example, shift workers).
4. Undergoing current treatment for hepatitis B with interferon.
5. Has a risk of suicide according to endorsement of Item 4 or 5 of the screening visit Columbia Suicide Severity Rating Scale (C-SSRS) or has made a suicide attempt in the previous 6 months.
6. Has medical condition, such as past or current epilepsy, seizure, head injury/trauma, medically significant unstable cardiovascular, pulmonary, hepatic, renal, or gastrointestinal disease, that interferes with a normal sleep pattern or would preclude enrollment in the view of the investigator.
7. Has a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia.
8. As of the screening visit and throughout the study, the participant should not be a chronic caffeine user, as defined by an excessive (greater than [>] 600 milligram [mg]/day) caffeine intake per day.
9. Has a medical disorder (other than narcolepsy), associated with excessive daytime sleepiness. This includes clinically significant obstructive sleep apnea or other sleep disturbances that has a significant impact on daytime sleepiness, confirmed by past PSG data (example, apnea hypopnea index >=10, periodic limb movement disorder index in sleep >=15) or a periodic limb movement disorder arousal index of >=10, or as evaluated on interview at the screening visit. Because nPSG data is obtained on Day 1, participants may be removed from study if they meet the above exclusion at the discretion of the principal investigator. Participants removed under this criterion will be replaced.
10. At the time of screening the participant is being treated with nasal or oro-nasal positive airway pressure for any reason.
11. Is currently being prescribed sodium oxybate or has been off of sodium oxybate for less than 4 weeks.
12. Is using varenicline (Chantix).

Contacts and Locations

Locations

United States, California

Stanford School of Medicine

Redwood City, California, United States, 94063

United States, Colorado

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, United States, 80918

United States, Florida

St Francis Medical Institute

Clearwater, Florida, United States, 33765

United States, Georgia

NeuroTrials Research, Inc.

Atlanta, Georgia, United States, 30328

United States, Indiana

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States, 46804

United States, New York

Sleep Wake Disorders Center

Bronx, New York, United States, 10467

United States, North Carolina

Research Carolina Elite, LLC

Denver, North Carolina, United States, 28037

United States, Ohio

CTI Clinical Trial and Consulting Services

Cincinnati, Ohio, United States, 45212

Intrepid Research

Cincinnati, Ohio, United States, 45245

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Ohio Sleep Medicine Institute

Dublin, Ohio, United States, 43017

United States, South Carolina

Bogan Sleep Consultants, LLC

Columbia, South Carolina, United States, 29201

United States, Texas

Sleep Therapy & Research Center

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Takeda

Takeda Development Center Americas, Inc.

Investigators

• Study Director: Medical Director; Takeda Development Center Americas, Inc.

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04445129
• Other Study ID Numbers: TAK-994-0001; U1111-1251-7993 ( Registry Identifier: WHO )
• First Posted: June 24, 2020
• Last Update Posted: May 7, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Narcolepsy; Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders