Bipolar DisorderNCT03656302
Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder
An observational study of Bipolar Disorder, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
This study aims to 1) investigate the differences and variances in circadian rhythms at several levels, including physical activity, dim light melatonin onset, diurnal patterns of cortisol, and body temperature between the offspring of patients with bipolar disorder (BD) and offspring of healthy parents by using a… Read more about this study
- Who is it for?
- Ages 6 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- How many people
- 1,000 participants
- Where
- 1 siteHong Kong
- Study dates
- 11 Feb 2017to 28 Jun 2020
- 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 6 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Patients with BD will be recruited from psychiatry outpatient clinics in Hong Kong and mainland China. Healthy parents will be recruited from our on-going community-based projects. In addition, the investigators will also recruit subjects through public advertisement through various media such as Facebook, poster, and emails. In view of the potential sex differences in these circadian rhythms indicators of interest, the adolescent offspring of healthy parents will be age- and sex-matched to the adolescent offspring of BD parents.
Who may be able to join
- 1) aged 6-21 years old; 2) having at least one biological parent with a lifetime or current diagnosis of bipolar disorder; 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form
- 1) aged 6-21 years old; 2) having no biological parent(s) with lifetime or current diagnosis of mood disorders. 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form.
Who cannot join
- 1) having lifetime history or current diagnosis of bipolar disorder; 2) having no good ability to attend this project, such as patients with dementia and mental retardation.
- 2. Control offspring
- 1) having lifetime history or current diagnosis of bipolar disorder. 2) having no good ability to attend this project, such as patients with dementia and mental retardation.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong
Hong Kong
Jihui Zhang, PhD
About this study
This study aims to 1) investigate the differences and variances in circadian rhythms at several levels, including physical activity, dim light melatonin onset, diurnal patterns of cortisol, and body temperature between the offspring of patients with bipolar disorder (BD) and offspring of healthy parents by using a high-risk study design; and 2) determine whether these indicators correlate with psychopathological symptoms as measured by the psychometric measurements.
Read the detailed description
Bipolar disorder (BD), characterized by episodes of mania or hypomania with frequent depressive episodes, is commonly found in the general population with a lifetime prevalence of 1-2% in the world. The morbidities and mortality associated with bipolar disorder are huge and the repercussion on their family members is considerate. Nonetheless, there is no existing well-established prevention strategy that may prevent this distressing mental disorder. A major reason is that there was limited understanding of the prodromal phase of BD. On the other hand, the genetic background determines about 60-85% of risk variance of BD. In other words, the offspring carries significant risk and propensity to develop future BD. Limited existing studies suggested that offspring of patients with BD have a higher rate of sleep and circadian disturbances and mental disorders than those offspring of parents without BD. Nonetheless, it is still unclear whether sleep and circadian disturbances are prodromal markers or risk factors for the development of bipolar disorder in this high-risk population.
In light of our research and other studies' preliminary findings on the relationship between circadian rhythms dysregulation and BD and robust heritability in BD, we hypothesize that
- Circadian rhythm dysregulations are prodromal features and endophenotypes of BD. The offspring of BD parents will have more circadian rhythm dysregulations than those offspring of healthy controls;
- The biologic indices of circadian rhythm dysregulations will be correlated with subsyndromal psychopathology.
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar disorder, Circadian Rhythm Disorders, High-risk offspring, Endophenotypes
- Medical subject headings
- Bipolar Disorder, Chronobiology Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case offspring | Inclusion criteria: 1) aged 6-21 years old; 2) having at least one biological parent with a lifetime or current diagnosis of bipolar disorder; 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form Exclusion criteria: 1) having lifetime history or current diagnosis of bipolar disorder; 2) having no good ability to attend this project, such as patients with dementia and mental retardation. | |
| Control offspring | Inclusion criteria: 1) aged 6-21 years old; 2) having no biological parent(s) with lifetime or current diagnosis of mood disorders. 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form. Exclusion criteria: 1) having lifetime history or current diagnosis of bipolar disorder. 2) having no good ability to attend this project, such as patients with dementia and mental retardation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dim light melatonin onset (DLMO, free day)
The subjects will be instructed to arrive at our sleep laboratory 9 hours before their usual bedtime. Saliva samples will be collected into clear sterile tubes every 30 minutes for eight hours, starting six hours before and 2 hours after individual's habitual bedtime. Subjects will be asked to stay in the light-controlled study room (<30 lux in any direction of gaze) and remain awake and sit quietly.
Measured: 9 hours
Secondary outcomes (6)
Actigraphy and sleep diary
One-week Actigraphy (GENEActiv) and sleep diary will be employed to continuously measure sleep/wake patterns and physical activity.
Measured: one week
Body temperature
Consecutive one-week period Skin temperature will be measured by iButton DS1921H (Dallas, Maxim) at 3 places: right on the middle of the frontal aspect of the thigh, abdomen (1 cm above the navel), and the right infraclavicular area. It has been demonstrated that iButton has satisfactory validity, reliability, and utility in the measurements of circadian rhythms and sleep/wake cycles.
Measured: one week
Circadian rhythm pattern of salivary cortisol (free day)
Subjects will be instructed to collect saliva samples using salivettes upon awakening (0 minute, 15 minutes, 30 minutes, and 45 minutes to measure cortisol awakening response) and then every 4 hours to measure the circadian rhythm patterns of cortisol secretion.
Measured: 24 hours
24-Hour Urinary 6-sulphatoxymelatonin (aMT6s) Assessment
During the night of DLMO measure, all subjects will be instructed to collect a 24-h urinary samples (nearly 1000 mL) for the urinary 6-sulfatoxymelatonin assessment.
Measured: 24 hours
Sleep macroarchitecture by polysomnography
One-night polysomnographic assessment will be measured to document the sleep architecture, together with DLMO measure. The recordings include electro-oculogram (EOG), electroencephalogram (EEG), electromyogram (EMG; monitoring over chin and bilateral anterior tibialis muscles), electrocardiogram (ECG), nasal-oral airflow and respiratory movements. The PSG data will be scored according to the most updated scoring manual of the American Academy of Sleep Medicine.
Measured: One-night (nearly 8 hours)
The rates of chronotype and sleep disorders
Chronotype will be estimated by the Morningness-eveningness Questionnaire (MEQ) or the Children's ChronoType Questionnaire (CCTQ). Sleep disorders, such as insomnia and delayed sleep phase disorder, will be also determined by the Diagnostic Interview for Sleep Patterns and Disorders (DISP).
Measured: nearly one hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2018
- Study start11 Feb 2017
- Primary completion28 Feb 2020 (estimated)
- Study completion28 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Kowloon Hospital, Hong Kong, The First Affiliated Hospital of Guangzhou Medical University, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen Baoan Center for Chronic Disease Control, Shenzhen Longgang Center for Chronic Disease Control, Shenzhen Futian Center for Chronic Disease Control
- Responsible party
- Principal investigator, Dr. Zhang Jihui, Chinese University of Hong Kong
- Investigators
- Jihui Zhang, PhD, Principal investigator, Chinese University of Hong KongYun Kwok Wing, MBChB, Study chair, Chinese University of Hong KongSiu Ping Lam, Study director, Shatin HospitalShirley Xin Li, PhD, Study director, Hong Kong UniversityRoger Man Kin Ng, PhD, Study director, Kowloon Hospital, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03656302
- Sponsor's protocol ID
- 03140636
- Status last verified
- Aug 2018
- First submitted
- 5 Jul 2018
- Last updated
- 4 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lei B, Feng H, Yang L, Wang J, Chen J, Song W, Jiang C, Zhang K, Wang Q, Tsang JCC, Chan NY, Liu Y, Chan JWY, Pan J, Zhang B, Li T, Merikangas KR, Zhang J, Wing YK. Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder: a high-risk study in the Chinese population. Gen Psychiatr. 2024 May 22;37(3):e101239. doi: 10.1136/gpsych-2023-101239. eCollection 2024.
PubMed 38800632
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder
- ClinicalTrials.gov ID
- NCT03656302
- Acronym / sponsor ID
- 03140636
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar disorder, Circadian Rhythm Disorders, High-risk offspring, Endophenotypes
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- Kowloon Hospital, Hong Kong, The First Affiliated Hospital of Guangzhou Medical University, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen Baoan Center for Chronic Disease Control, Shenzhen Longgang Center for Chronic Disease Control, Shenzhen Futian Center for Chronic Disease Control
- Study start
- 11 Feb 2017 (actual)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 28 Jun 2020 (estimated)
- First posted
- 4 Sep 2018 (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.
This study aims to 1) investigate the differences and variances in circadian rhythms at several levels, including physical activity, dim light melatonin onset, diurnal patterns of cortisol, and body temperature between the offspring of patients with bipolar disorder (BD) and offspring of healthy parents by using a high-risk study design; and 2) determine whether these indicators correlate with psychopathological symptoms as measured by the psychometric measurements.
Detailed description
Bipolar disorder (BD), characterized by episodes of mania or hypomania with frequent depressive episodes, is commonly found in the general population with a lifetime prevalence of 1-2% in the world. The morbidities and mortality associated with bipolar disorder are huge and the repercussion on their family members is considerate. Nonetheless, there is no existing well-established prevention strategy that may prevent this distressing mental disorder. A major reason is that there was limited understanding of the prodromal phase of BD. On the other hand, the genetic background determines about 60-85% of risk variance of BD. In other words, the offspring carries significant risk and propensity to develop future BD. Limited existing studies suggested that offspring of patients with BD have a higher rate of sleep and circadian disturbances and mental disorders than those offspring of parents without BD. Nonetheless, it is still unclear whether sleep and circadian disturbances are prodromal markers or risk factors for the development of bipolar disorder in this high-risk population.
In light of our research and other studies' preliminary findings on the relationship between circadian rhythms dysregulation and BD and robust heritability in BD, we hypothesize that
- Circadian rhythm dysregulations are prodromal features and endophenotypes of BD. The offspring of BD parents will have more circadian rhythm dysregulations than those offspring of healthy controls;
- The biologic indices of circadian rhythm dysregulations will be correlated with subsyndromal psychopathology.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case offspring | – | –Inclusion criteria: 1) aged 6-21 years old; 2) having at least one biological parent with a lifetime or current diagnosis of bipolar disorder; 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form Exclusion criteria: 1) having lifetime history or current diagnosis of bipolar disorder; 2) having no good ability to attend this project, such as patients with dementia and mental retardation. |
| Control offspring | – | –Inclusion criteria: 1) aged 6-21 years old; 2) having no biological parent(s) with lifetime or current diagnosis of mood disorders. 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form. Exclusion criteria: 1) having lifetime history or current diagnosis of bipolar disorder. 2) having no good ability to attend this project, such as patients with dementia and mental retardation. |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Patients with BD will be recruited from psychiatry outpatient clinics in Hong Kong and mainland China. Healthy parents will be recruited from our on-going community-based projects. In addition, the investigators will also recruit subjects through public advertisement through various media such as Facebook, poster, and emails. In view of the potential sex differences in these circadian rhythms indicators of interest, the adolescent offspring of healthy parents will be age- and sex-matched to the adolescent offspring of BD parents.
Key inclusion criteria (2 listed)
- 1) aged 6-21 years old; 2) having at least one biological parent with a lifetime or current diagnosis of bipolar disorder; 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form
- 1) aged 6-21 years old; 2) having no biological parent(s) with lifetime or current diagnosis of mood disorders. 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form.
Key exclusion criteria (3 listed)
- 1) having lifetime history or current diagnosis of bipolar disorder; 2) having no good ability to attend this project, such as patients with dementia and mental retardation.
- 2. Control offspring
- 1) having lifetime history or current diagnosis of bipolar disorder. 2) having no good ability to attend this project, such as patients with dementia and mental retardation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Dim light melatonin onset (DLMO, free day)
Time frame: 9 hours
The subjects will be instructed to arrive at our sleep laboratory 9 hours before their usual bedtime. Saliva samples will be collected into clear sterile tubes every 30 minutes for eight hours, starting six hours before and 2 hours after individual's habitual bedtime. Subjects will be asked to stay in the light-controlled study room (<30 lux in any direction of gaze) and remain awake and sit quietly.
6 secondary outcomes
Actigraphy and sleep diary
Time frame: one week
Body temperature
Time frame: one week
Circadian rhythm pattern of salivary cortisol (free day)
Time frame: 24 hours
24-Hour Urinary 6-sulphatoxymelatonin (aMT6s) Assessment
Time frame: 24 hours
Sleep macroarchitecture by polysomnography
Time frame: One-night (nearly 8 hours)
The rates of chronotype and sleep disorders
Time frame: nearly one hour
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2018.
- Derived from this study: PubMed 38800632Lei B, Feng H, Yang L, Wang J, Chen J, Song W, Jiang C, Zhang K, Wang Q, Tsang JCC, Chan NY, Liu Y, Chan JWY, Pan J, Zhang B, Li T, Merikangas KR, Zhang J, Wing YK. Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder: a high-risk study in the Chinese population. Gen Psychiatr. 2024 May 22;37(3):e101239. doi: 10.1136/gpsych-2023-101239. eCollection 2024.
- Individual participant dataSharing planned: Undecided
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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.
Jihui Zhang, PhD principal investigator
Chinese University of Hong Kong
Yun Kwok Wing, MBChB study chair
Chinese University of Hong Kong
Siu Ping Lam study director
Shatin Hospital
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 Bipolar Disorder, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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 3 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: status not confirmed, as of the sponsor's last update on 4 Sep 2018. 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 Hong Kong. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jihui Zhang, PhD ((852) 39197647, jihui.zhang@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dim light melatonin onset (DLMO, free day) (time frame: 9 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03656302, which also lists 1 linked publication.
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 4 Sep 2018.