Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03656302
• Other study ID #: 03140636
• Status: Recruiting
• Start date: February 11, 2017
• Est. completion date: June 28, 2020

Study information

• Verified date: August 2018
• Source: Chinese University of Hong Kong
• Contact: Jihui Zhang, PhD
• Phone: (852) 39197647
• Email: jihui.zhang[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Observational

Clinical 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 high-risk study design; and 2) determine whether these indicators correlate with psychopathological symptoms as measured by the psychometric measurements.

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

1. 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;

2. The biologic indices of circadian rhythm dysregulations will be correlated with subsyndromal psychopathology.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 28, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

1. 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.

2. 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.

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease

Locations

Country	Name	City	State
Hong Kong	Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong	Hong Kong

Sponsors (7)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Kowloon Hospital, Shenzhen Baoan Center for Chronic Disease Control, Shenzhen Futian Center for Chronic Disease Control, Shenzhen Longgang Center for Chronic Disease Control, Shenzhen Nanshan Center for Chronic Disease Control, The Affiliated Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital)

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	9 hours
Secondary	Actigraphy and sleep diary	One-week Actigraphy (GENEActiv) and sleep diary will be employed to continuously measure sleep/wake patterns and physical activity.	one week
Secondary	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.	one week
Secondary	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.	24 hours
Secondary	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.	24 hours
Secondary	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.	One-night (nearly 8 hours)
Secondary	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).	nearly one hour