Validation of Circadian Biomarkers in Patients With Sleep Disorders

NCT04690504 | Completed

• 1 other identifier: 2020-P-000606
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Current methods for assessing circadian timing require sampling over hours (or even up to a day) while the patient is in controlled conditions. The investigators aim to develop a method that can estimate individual circadian time with a single blood sample taken at any time of the day or night. To do this, the investigators will use two state of the art methods, a plasma proteomics-based method to identify a panel of rhythmic proteins (extending our preliminary data) and a whole blood-derived monocyte-based method using a panel of 15 transcripts (to validate and extend a recent study). We will test both methods in a series of patients with circadian rhythm sleep disorders. We will validate separately the proteomics-based biomarker and the monocyte-based transcript biomarker, and also explore whether combining them can improve the accuracy of our timing estimates. In all cases, circadian phase estimates from the biomarker panels will be compared with those derived from plasma or saliva melatonin (the current "gold-standard" circadian phase marker).

Conditions

Sleep Disorders, Circadian Rhythm; Circadian Rhythm Disorders; Circadian Rhythm Sleep Disorder; Advanced Sleep Phase Syndrome (ASPS); Delayed Sleep Phase Syndrome; Sleep Wake Disorders; Sleep Disorder

Keywords

ASWPD, DSWPD, CRSWD, melatonin, circadian, circadian rhythm, biomarker

Outcome Measures

Primary Outcomes (3)

• DLMO

  dim light melatonin onset, the time at which melatonin levels in the saliva rise above 3pg/mL

  Study Day 1

• BodyTime

  the time at which a series of rhythmic gene transcripts predict circadian phase

  Study Day 1

• PlasmaTime

  the time at which a series of rhythmic proteins predict circadian phase

  Study Day 1

Interventions

dim light melatonin onset (DLMO) OTHER

A series of saliva samples will be collected and assayed for melatonin so that the timing of melatonin secretion onset can be determined.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy adults who meet ICSD-3 criteria for Advanced Sleep Wake Phase Disorder (ASWPD) or Delayed Sleep Wake Phase Disorder (DSWPD).

You may qualify if:

• ICSD3 diagnosis of Advanced Sleep-Wake Phase Disorder or Delayed Sleep-Wake Phase Disorder
• otherwise healthy

You may not qualify if:

• history of drug or alcohol dependency
• a sleep disorder other than a circadian rhythm sleep disorder
• use of medications that interfere with melatonin production (e.g., beta blockers) within the past month
• night shift work (for ASWPD patients) or early morning starts (for DSWPD patients) in the prior 3 years
• recent (within 3 months) travel to a place 2 time zones or greater away from home
• acute or uncontrolled medical conditions
• major visual deficit
• active or uncontrolled psychological or psychiatric disorder
• use of exogenous melatonin or melatonin agonists within the past month

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Stanford University: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples will be collected and assayed for melatonin. Blood samples will be collected and assayed for rhythmic gene transcripts and rhythmic proteins. A blood sample will be collected for DNA analysis, including potential GWAS.

MeSH Terms

Conditions

Sleep Disorders, Circadian Rhythm; Chronobiology Disorders; Sleep Wake Disorders

Condition Hierarchy (Ancestors)

Nervous System Diseases; Dyssomnias; Occupational Diseases; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Emmanuel Mignot, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Investigator

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 30, 2020
• Study Start: November 2, 2021
• Primary Completion: June 30, 2024
• Study Completion: July 1, 2024
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)