Sleep Disorders, Circadian RhythmNCT04690504
Validation of Circadian Biomarkers in Patients With Sleep Disorders
An observational study of Sleep Disorders, Circadian Rhythm and Circadian Rhythm Disorders, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sleep Disorders, Circadian Rhythm, Circadian Rhythm Disorders, Circadian Rhythm Sleep Disorder
- What is being tested?
- dim light melatonin onset (DLMO)
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2021to 1 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Adult, Older adult
Study population: Healthy adults who meet ICSD-3 criteria for Advanced Sleep Wake Phase Disorder (ASWPD) or Delayed Sleep Wake Phase Disorder (DSWPD).
Who may be able to join
- ICSD3 diagnosis of Advanced Sleep-Wake Phase Disorder or Delayed Sleep-Wake Phase Disorder
- otherwise healthy
Who cannot join
- 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
Show all 9Show fewer
- major visual deficit
- active or uncontrolled psychological or psychiatric disorder
- use of exogenous melatonin or melatonin agonists within the past month
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Proteomic and Transcriptomic Biomarkers of Circadian Timing - Validation of Circadian Biomarkers in Patients With Sleep Disorders
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).
Read the detailed description
Adults who meet ICSD-3 criteria for Advanced Sleep Wake Phase Disorder or Delayed Sleep Wake Phase Disorder will be studied at Brigham and Women's Hospital and Stanford University.
The outpatient protocol will consist of two segments: clinic visit and in-home saliva sample collection. For the first segment, the patient participant will be scheduled for a daytime visit to the sleep clinic where they will have blood drawn for protein and monocyte analysis after having kept a sleep diary and worn a wrist activity monitor for at least 1 week. The patient participant will be provided with an at-home saliva sampling kit and instructed in its use, in particular how to maintain appropriate dim light conditions. For the second segment, the patient will be instructed to collect the series of saliva samples on that same evening, collecting a saliva sample each hour beginning 7 hours before their usual bedtime and ending one hour after their usual bedtime. As each sample is collected, the patient participant will document the tube number and clock time on a log that the investigators provide them, and the patient participant will store each sample in a zip lock bag in their home freezer until the next day. After waking the next day, the patient will pack their samples in the insulated shipping box they were provided, along with their sample collection log and freezer packs they were provided, and then they call a courier to pick up the box, which is sent directly to the assay facility.
Alternatively, patients may be given the opportunity to come for a single extended visit at the laboratory or clinic. This visit will include the blood sampling for protein and monocyte analysis, followed by 8 hours in which they remain in dim lighting conditions in the lab or clinic and provide a saliva sample each hour. The saliva sampling segment will begin 7 hours before their usual bedtime and ending one hour after their usual bedtime. After the final saliva sample the study will be over and the patient will be allowed to go home.
- Conditions
- Sleep Disorders, Circadian Rhythm, Circadian Rhythm Disorders, Circadian Rhythm Sleep Disorder, Advanced Sleep Phase Syndrome (ASPS), Delayed Sleep Phase Syndrome, Sleep Wake Disorders
- Being tested
- dim light melatonin onset (DLMO)
- Keywords
- ASWPD, DSWPD, CRSWD, melatonin, circadian, circadian rhythm, biomarker
- Medical subject headings
- Sleep Disorders, Circadian Rhythm, Chronobiology Disorders, Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
DLMO
dim light melatonin onset, the time at which melatonin levels in the saliva rise above 3pg/mL
Measured: Study Day 1
BodyTime
the time at which a series of rhythmic gene transcripts predict circadian phase
Measured: Study Day 1
PlasmaTime
the time at which a series of rhythmic proteins predict circadian phase
Measured: Study Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2020
- Study start2 Nov 2021
- Primary completion30 Jun 2024
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Disorders, Circadian RhythmStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University
- Responsible party
- Principal investigator, Jeanne Duffy, Brigham and Women's Hospital
- Investigators
- Emmanuel Mignot, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04690504
- Sponsor's protocol ID
- 2020-P-000606
- Status last verified
- Aug 2024
- First submitted
- 15 Dec 2020
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proteomic and Transcriptomic Biomarkers of Circadian Timing - Validation of Circadian Biomarkers in Patients With Sleep Disorders
- ClinicalTrials.gov ID
- NCT04690504
- Acronym / sponsor ID
- 2020-P-000606
- Conditions
- Sleep Disorders, Circadian Rhythm, Circadian Rhythm Disorders, Circadian Rhythm Sleep Disorder, Advanced Sleep Phase Syndrome (ASPS), Delayed Sleep Phase Syndrome, Sleep Wake Disorders
- Keywords
- ASWPD, DSWPD, CRSWD, melatonin, circadian, circadian rhythm, biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Stanford University
- Study start
- 2 Nov 2021 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 30 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Adults who meet ICSD-3 criteria for Advanced Sleep Wake Phase Disorder or Delayed Sleep Wake Phase Disorder will be studied at Brigham and Women's Hospital and Stanford University.
The outpatient protocol will consist of two segments: clinic visit and in-home saliva sample collection. For the first segment, the patient participant will be scheduled for a daytime visit to the sleep clinic where they will have blood drawn for protein and monocyte analysis after having kept a sleep diary and worn a wrist activity monitor for at least 1 week. The patient participant will be provided with an at-home saliva sampling kit and instructed in its use, in particular how to maintain appropriate dim light conditions. For the second segment, the patient will be instructed to collect the series of saliva samples on that same evening, collecting a saliva sample each hour beginning 7 hours before their usual bedtime and ending one hour after their usual bedtime. As each sample is collected, the patient participant will document the tube number and clock time on a log that the investigators provide them, and the patient participant will store each sample in a zip lock bag in their home freezer until the next day. After waking the next day, the patient will pack their samples in the insulated shipping box they were provided, along with their sample collection log and freezer packs they were provided, and then they call a courier to pick up the box, which is sent directly to the assay facility.
Alternatively, patients may be given the opportunity to come for a single extended visit at the laboratory or clinic. This visit will include the blood sampling for protein and monocyte analysis, followed by 8 hours in which they remain in dim lighting conditions in the lab or clinic and provide a saliva sample each hour. The saliva sampling segment will begin 7 hours before their usual bedtime and ending one hour after their usual bedtime. After the final saliva sample the study will be over and the patient will be allowed to go home.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Healthy adults who meet ICSD-3 criteria for Advanced Sleep Wake Phase Disorder (ASWPD) or Delayed Sleep Wake Phase Disorder (DSWPD).
Key inclusion criteria (2 listed)
- ICSD3 diagnosis of Advanced Sleep-Wake Phase Disorder or Delayed Sleep-Wake Phase Disorder
- otherwise healthy
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dim light melatonin onset (DLMO)A series of saliva samples will be collected and assayed for melatonin so that the timing of melatonin secretion onset can be determined. | Other | – |
Primary outcome
DLMO
Time frame: Study Day 1
dim light melatonin onset, the time at which melatonin levels in the saliva rise above 3pg/mL
BodyTime
Time frame: Study Day 1
the time at which a series of rhythmic gene transcripts predict circadian phase
PlasmaTime
Time frame: Study Day 1
the time at which a series of rhythmic proteins predict circadian phase
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuel Mignot, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sleep Disorders, Circadian Rhythm and Circadian Rhythm Disorders, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLMO (time frame: Study Day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.