STEP-MDD: Multi-Dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03219008

Collaborator

Shanghai Jiao Tong University School of Medicine (Other), Chinese Academy of Sciences (Other), Shanxi Medical University (Other), Central South University (Other), Second Military Medical University (Other), Peking University Sixth Hospital (Other), First Affiliated Hospital Xi'an Jiaotong University (Other), The First Affiliated Hospital of Kunming Medical College (Other), Air Force Military Medical University, China (Other), Zhejiang University (Other), Wuhan Mental Health Centre (Other), Corning Hospital, Shenzhen City (Other), the First Specialized Subject Hospital of Harbin (Other), Renmin Hospital of Wuhan University (Other), Seventh People's Hospital of Hangzhou (Other), Shandong Mental Health Center (Other)

800

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Major Depressive Disorder is one of the most common mental diseases,which increases health-care costs and the financial burden to families and societies. Considering its complex clinical symptoms and diversity of comorbidity, depressive disorder's recognition，diagnosis，and antihistone are based on symptomatology,which is lack of multidimensional diagnosis technique based on clinical pathological characteristics,as well as lack of individualized therapy strategy based on quantified evaluation. Besides, other physical diseases，such as nervous system diseases, cardiovascular diseases，endocrine diseases, have the high comorbidity of depressive disorder. However，there is no precise diagnosis technique or standardized therapy strategy. With all those taken into consideration,our study is aimed to adopt E-mental health and m-Health to explore multi-dimensional diagnosis, individualized therapy and management technique based on molecular biology,nerve electrophysiology，and neuroimaging technology etc.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder	Drug: Fluoxetine Combination Product: fluoxetine + cognitive-behavioral treatment（CBT） Drug: fluoxetine + Amfebutamone Combination Product: physical treatment+fluoxetine+amfebutamone Drug: Fluvoxamine Drug: Lithium+fluvoxamine Combination Product: fluvoxamine + lithium + physical therapy Combination Product: Cognitive behavior treatment +fluvoxamine Drug: Mirtazapine/SNRIs Combination Product: mirtazapine+ Cognitive behavior treatment Drug: mirtazapine + SNRIs Combination Product: mirtazapine + SNRIs + physical therapy Other: TAU(treat as usual)	Phase 4

Detailed Description

Four parts included in our study:

Part 1:The research, development and verification of indicators based on biomarkers and clinical characteristics to guide the diagnosis and treatment of depressive disorders

to screen biomarkers, to explore its pathophysiology, and to analyze the correlation between clinical subtypes/characteristics and biomarkers.
To differentiate the subtypes of depressive disorder（depression/underload, atypical, anxiety/somatization) based on clinical symptoms and clinical assessement.
To establish personalized therapy strategies,and to explore tool kits for diagnosis and treatment based on biomarkers and clinical characteristics.
to choose appropriate indicators to monitor therapy and side effect by collecting and analyzing blood/imaging/neuropsychological data.

Part 2: The development,transition and application of hierarchical model diagnostic technique for physical diseases combined with depressive disorder.

to recruit patients with physical diseases combined with depressive disorder, and explore potential biomarkers.
To chose appropriate therapy strategies based on measurement based care（MBC）, providing hierarchical model diagnostic technique for patients.
To weigh therapy efficiency and adverse effect among different medicine therapy groups.

Part3: The development and application of comprehensive prevention， diagnosis,and intervention model of depressive disorder.

To explore and establish online screening and assistant diagnosis system for patients with depressive disorder.
research ,development and application of intelligent e-MBC. Part 4: The development,transition and application of e-MBC sharing platform.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Part 2: all patients before receiving any medicine treatment are divided into four groups which adopt different therapy strategies :treatment with fluvoxamine, fluoxetine, mirtazapine and treatment as usual(TAU).Meanwhile，patients with different subtypes of depressive disorder were randomly assigned to different therapy groups.Each therapy groups contains 50 participants.Therefore, the total sample size is 50*12+200=800. Part3:To find out efficiency of different kinds of therapy strategies.p=60%, error=5%,a-0.05,the amount of samples nearly is:867,considering the nearly 30% expulsion rate, the final total sample size is 867+260=1127.Therefore,sample size in each group is nearly 376. Part4:p=60%,error=0.05, a=0.05, exculsion rate=30%,N=867+260=1127.the amount of samples of each group is 1127/3=nearly 400.Part 2: all patients before receiving any medicine treatment are divided into four groups which adopt different therapy strategies :treatment with fluvoxamine, fluoxetine, mirtazapine and treatment as usual(TAU).Meanwhile，patients with different subtypes of depressive disorder were randomly assigned to different therapy groups.Each therapy groups contains 50 participants.Therefore, the total sample size is 50*12+200=800. Part3:To find out efficiency of different kinds of therapy strategies.p=60%, error=5%,a-0.05,the amount of samples nearly is:867,considering the nearly 30% expulsion rate, the final total sample size is 867+260=1127.Therefore,sample size in each group is nearly 376. Part4:p=60%,error=0.05, a=0.05, exculsion rate=30%,N=867+260=1127.the amount of samples of each group is 1127/3=nearly 400.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

patients with depressive disorder were randomly assigned to different therapy groups or TAU therapy group based on different depressive disorders subtypes.

Primary Purpose:

Treatment

Official Title:

Multi-dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics

Actual Study Start Date :

Aug 1, 2017

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Depression/underload 1 This group would be treated with fluoxetine from the minimum dosage.	Drug: Fluoxetine Fluoxetine is one kind of selective serotonin reuptake inhibitor(SSRIs), whose effect is much better than other non-underload subtypes compared with underload subtypes.So patients would be treated with fluoxetine only.
Experimental: Depression/underload 2 This group would be treated with fluoxetine combined with cognitive behavior treatment	Combination Product: fluoxetine + cognitive-behavioral treatment（CBT） the investigators would recommend fluoxetine to help to cure depressive disorder.And CBT is a very effective way for patients to alleviate or relieve clinical symptoms during episode stage.
Experimental: Depression/underload 3 This group would be treated with fluoxetine and amfebutamone from the minimum dosage.	Drug: fluoxetine + Amfebutamone Amfebutamone is one kind of SNRIs, and it shows much better therapy effect on patients with exhaustion /dizziness.So the investigators recommend these two drugs to help to cure patients with depressive disorder.
Experimental: Depression/underload 4 This group would be treated with fluoxetine + physical treatment to help to cure depressive disorder.	Combination Product: physical treatment+fluoxetine+amfebutamone the investigators recommend drug(fluoxetine and amfebutamone) and physical treatment as intervention.
Experimental: Atypical 1 This group would be treated with fluvoxamine from the minimum dosage.	Drug: Fluvoxamine Fluvoxamine could inhibit CYP1A2 and CYP2C19 and affect the metabolism of melatonin, and help to release symptoms of depressive disorder with sleep problems.
Experimental: Atypical 2 This group would be treated with fluoxetine + cognitive behavior treatment	Combination Product: Cognitive behavior treatment +fluvoxamine the investigators recommend behavioral therapy as well as drugs.
Experimental: Atypical 3 This group would be treated with fluvoxamine + lithium from the minimum dosage.	Drug: Lithium+fluvoxamine the investigators recommend lithium as a mood stabilizer and use fluvoxamine to affect the level of melatonin.
Experimental: Atypical 4 This group would be treated with fluvoxamine + lithium + physical treatment	Combination Product: fluvoxamine + lithium + physical therapy the investigators recommend depressants and mood stabilizers as well as physical therapy to help to cure depressive disorder.
Experimental: Anxiety/somatization 1 This group would be treated with mirtazapine/selective serotonin-norepinephrine reuptake inhibitors（SNRIs） from the minimum dosage.	Drug: Mirtazapine/SNRIs Mirtazapine is one kind of antagonist of a2 adrenergic receptors and could block 5-hydroxytryptamine2 and 5-hydroxytryptamine3,help to release symptoms like anxiety or somatization.Besides, SNRIs could also make similar effect on patients.Therefore, the investigators recommend mirtazapine/SNRIs to treat patients with depressive disorder.
Experimental: Anxiety/somatization 2 This group would be treated with mirtazapine/SNRIs + cognitive behavior treatment.	Combination Product: mirtazapine+ Cognitive behavior treatment the investigators recommend CBT and mirtazapine as interventions.The dosage and frequency would depend on patients' severity of symptoms .
Experimental: Anxiety/somatization 3 This group would be treated with mirtazapine + SNRIs from the minimum dosage.	Drug: mirtazapine + SNRIs the investigator recommend mirtazapine and SNRIs to treat patients with major depressive disorder.
Experimental: Anxiety/somatization 4 This group would be treated with mirtazapine + SNRIs + physical treatment.	Combination Product: mirtazapine + SNRIs + physical therapy the investigators would manage to use drugs and physical treatment to help to release the symptoms of depressive disorder.
Experimental: treatment as usual(TAU) The investigators recommend therapy strategies according to accessible methods.	Other: TAU(treat as usual) patients in this group would receive therapy strategies according to their symptoms and preference.

Outcome Measures

Primary Outcome Measures

Change from baseline in levels of microRNA，apolipoproteins, meta ion (Composite measure) [at 2,4,6,8,12 week.]
The potential biomarkers in our study include microRNA,apolipoproteins,metallic ion etc.We use quantitative analysis technique to test miRNA,proteins and metallic ion by patients' blood and urines before interventions and after interventions.

Secondary Outcome Measures

Hamilton Depression Scale(HADA) scores,reductive ratio [at 0,2,4,6,8,12 week.]
HADA,created by Hamilton in 1960,is one of the most common questionnaires to evaluate the severity of depression and the efficiency of medicine. we adopt the Hamilton Depression Scale(HADA)to evaluate different medicines efficiency by analyzing reductive ratio.The investigators record the total scores of HADA at baseline and 2,4,6,8,12 week.
Patient health questionnaire(PHQ-9):the clinical remission ratio [change from baseline PHQ-9 total scores at 2,4,6,8,12 week]
PHQ-9 is a self-report scale composed of 9 items to evaluate the state of depression.The investigators in our study record the total scores of PHQ-9 at 0,2,4,6,8,12 week to analyze the clinical remission ratio.
life event scale(LES) [at baseline]
LES is one of the common questionnaires to evaluate individual's mental and stress stimulation in daily life.The investigators record the total scores of LES at baseline.
social support scale(SSS) [at baseline]
SSS is one of the common questionnaires to evaluate individual's social support and social relationship network to explore the correlation between social support and mental health. the investigators in our study record the total scores of SSS at baseline.
dysfunctional attitudes scales(DAS) [at baseline]
The DAS is a self-report scale composed of 40 items to assess typical, stable depressogenic attitudes or schemas that make individuals vulnerable to depression. The investigators in our study record the total scores od DAS at baseline.
the gray matter volume, [change from baseline neuroimaging data at 2,4,6,8,12 week]
The investigators in our study use voxel-based morphometry (VBM8)to record the gray matter volume.
fractional amplitudes of low-frequency fluctuation(fLAFF) [change from baseline neuroimaging data at 2,4,6,8,12 week]
The investigators in our study use region-of-interest(ROI)to record fLAFF.
Neuroelectrophysiological examination: electroencephalogram(EEG) [at baseline]
EEG is used to record individual's brain activity. The investigators in our study record individual's brain wave.
Neuroelectrophysiological examination:electrocardiograph(ECG) [at baseline.]
ECG is used to record the individual's cardiac cycle.