Chinese Longitudinal and Systematic Study of Bioplar Disorder (CLASS-BD)

Affective disorders (mainly including major depressive disorder and bipolar disorder) are common, chronic and highly disabling mental disorders, which lack of objective biological markers. It is believed that genetic and environmental factors are involved in the development of affective disorders. Gut microbes can affect the function of brain neural circuits by mediating metabolic, immune, endocrine and autonomic changes along the brain-gut axis. The brain can also regulate intestinal microbes through endocrine, neural structure, neurogenic exosomes and other pathways. Based on the brain-gut axis, this study intends to establish a large cohort of affective disorders, and screen out efficient and convenient biomarkers for clinical diagnosis and efficacy prediction by studying key indicators such as intestinal microbes, serum metabolites and immune indexes, brain-derived exosomes, and brain functional imaging.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder; Bipolar Disorder, Mixed; Affective; Disorder, Organic
• Intervention / Treatment: Drug: Quetiapine Fumarate Tablets; Drug: Lurasidone; Drug: Escitalopram Oxalate Tablets

Detailed Description

Mental health is a major public health problem affecting the whole social and economic development. According to a 2019 report in The Lancet Psychiatry, the weighted lifetime prevalence of mental disorders (excluding dementia) in China is 16.6%, with the lifetime prevalence of emotional disorders as high as 7.4%.Affective disorders (mainly including depression and bipolar disorder) are common, chronic and highly disabling mental disorders.Back in 2008, the World Health Organization listed MDD（Major Depressive Disorder） as one of the three major contributors to the overall global burden of disease. It is expected that by 2030, the number of MDD patients will exceed the total number of cardiovascular disease patients combined and become the leading cause of disability in the world.

At present, the diagnostic criteria of mental disorders, including DSM-5 and ICD-11, still mainly rely on the evaluation of symptoms, lacking objective and intuitive biomarkers. Therefore psychiatrists are prone to disagreement in diagnosis and treatment of diseases, which is a realistic bottleneck hindering the development of psychiatry. The differential diagnosis of MDD and BD depressive episodes is an unavoidable clinical challenge, which often leads to misdiagnosis and affects the treatment and prognosis of the disease. Therefore, it is one of the important directions for the development of brain science to strengthen scientific research in the field of mental health, especially to explore the mechanism of disease occurrence and development, develop objective new auxiliary diagnostic technologies and innovate precise treatment strategies around major emotional disorders. It is believed that genetic and environmental factors are involved in the development of affective disorders. Gut microbes can affect the function of brain neural circuits by mediating metabolic, immune, endocrine and autonomic changes along the brain-gut axis. The brain can also regulate intestinal microbes through endocrine, neural structure, neurogenic exosomes and other pathways. This study based on brain - im axis, intends to create an emotional disorder large queue, through the study of gut microbes (diversity and abundance of species), serum metabolites, and immune index, brain outside source sex secretion, brain imaging and other key indicators, select high efficiency and convenient for clinical diagnosis and curative effect of prediction of biomarkers.

• Study Type: Interventional
• Enrollment (Anticipated): 10000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shaohua Hu; Phone Number: 086-13957162903; Email: dorhushaohua@zju.edu.cn
• Study Contact Backup: Name: Yanmeng Pan; Phone Number: 18868116237; Email: 12018602@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
      • Contact: Hu ShaoHua; Phone Number: 13957162903; Email: dorhushaohua@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Both biological parents are Han nationality;
2. Aged 16-65;
3. The subjects met the clinical diagnostic criteria of DSM-5 for depressive episodes of MDD/BD;
4. Did not take any immunomodulatory preparations within 1 month before enrollment;
5. No clear history of respiratory tract, urinary system, digestive system infection within 1 month before enrollment;

Exclusion Criteria:

1. Those with schizophrenia spectrum, neurodevelopmental disorder, dementia, memory impairment or other cognitive impairment that meet the DIAGNOSTIC criteria of DSM-5;
2. Mental disorders caused by substance abuse (alcohol, drugs, etc.), patients suffering from serious physical diseases and immune system diseases, such as diabetes, thyroid diseases, hypertension, heart disease, liver and kidney dysfunction, autoimmune diseases, etc.;
3. Had received medication (such as antidepressants, antipsychotics, mood stabilizers, etc.) within 1 month before enrollment;
4. those who had used ECT before enrollment;
5. Currently have serious suicidal thoughts or behaviors, or serious excitement;
6. those who cannot follow the doctor's advice or have no guardian;
7. pregnant or breast-feeding women, or those who plan to become pregnant;
8. Contraindications to MRI examination;
9. Other conditions that the researcher considers inappropriate for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bipolar disorder; Patients with BD depressive episode received standard treatment with quetiapine fumarate tablets, starting from 50mg/ night, titrated to a therapeutic dose of 300-400mg/ night within 10 days, and maintained treatment for 4 weeks. According to the patient's condition, patients with BD depressive episode could receive another standard treatment with lurasidone, starting from 20mg/ night, titrated to a therapeutic dose of 40mg/ night within 6 days, and maintained treatment for 4 weeks. Adverse reactions and changes in condition of all patients were recorded	Drug: Quetiapine Fumarate Tablets; Starting at 50mg qn, the treatment dose was titrated to 300-400mg qn within 10 days, and maintained the treatment for 4 weeks.; Other Names: Seroquel; Drug: Lurasidone; Starting at 20mg qn, the treatment dose was titrated to 40mg qn within 6 days,and maintained the treatment for 4 weeks.; Other Names: Latuda
Experimental: major depressive disorder; MDD depressive episode patients received standard treatment with escitalopram oxalate tablets, starting from 5mg/ day once, titrated to a therapeutic dose of 10-20mg/ day within 1 week, and maintained treatment for 4 weeks	Drug: Escitalopram Oxalate Tablets; Starting at 5mg qn, the treatment dose was titrated to 10-20mg qn within 1 week and maintained for 4 weeks; Other Names: Lexapro
No Intervention: healthy control; no interventions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale(MADRS)	MADRS score is to evaluate the degree of depression, and the higher score means severer depression.	0 ~16 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Affective Disorder; Bipolar Disorder; Major Depressive Disorder; Gut-Brain Axis
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Depression; Depressive Disorder; Disease; Bipolar Disorder; Mood Disorders; Depressive Disorder, Major; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Adrenergic alpha-Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Adrenergic alpha-2 Receptor Antagonists; Citalopram; Quetiapine Fumarate; Dexetimide; Lurasidone Hydrochloride
• Other Study ID Numbers: IIT20210291B-R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Arms and interventions can be shared, while the clinical data will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No