Bear Bile Pill as add-on the Treatment of MDD

Study Overview
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Brief Summary
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This is a single-center, double blind, randomized, placebo-controlled, parallel group study of bear bile pill, as add-on therapy in MDD patients conducted in Shang Hai Mental Health Center. The purpose of this study is to determine the efficacy and safety of bear bile pill in reducing symptoms of depression in Major Depressive Disorder (MDD)patients with inadequate response to current antidepressant therapy. Following a screening period, subjects who meet the entry criteria will be randomized to treated with either placebo or 450mg bear bile pill three times daily for 8 weeks.

Official Title
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Add-on Study of Bear Bile Pill for Patients With Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: bear bile pill
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition, Text Revision (DSM-V) criteria for Major Depressive Disorder (MDD); a single or recurrent episode without psychotic features ;Codes are as follows: F32.0、F32.1、F32.2、F33.0、F33.1 、F33.2. Outpatients or inpatients. Male or female subjects aged 18-65 years. Patients have got standard treatment of SSRI/SNRI monotherapy for more than 4 weeks in current episode of depression before trial entry. MADRS score greater than 20. Women of childbearing potential must be willing to use acceptable methods of contraception throughout the study period and the following one month. The patient the patient fully understand and signed the informed consent form Exclusion Criteria: Patient has survived a suicide attempt or has acute suicidal tendencies (MADRS Item 10 > 4). Comorbidity according to DSM-V, axis I except major depressive disorder. Failed 3 or more adequate antidepressant courses in current episode of depression. MADRS reduction ratio ≥25% within one week from the screening to the baseline Visit. Depressive episode secondary to psychiatric illness or somatic disease. Serious and instable body disease such as cerebrovascular disease, liver and kidney disease, disease of internal secretion (abnormal thyroid function), blood disease; any history of seizures or other organic brain diseases. History of alcohol or drug abuse over the last 6 months Allergic history to bear bile pills, or serious drug allergic history. Pregnant or lactating women and women of childbearing potential throughout the study period; men who have the desire of fertility within six months; Clinically significant changes in ECG or laboratory tests, including >1.5X upper limit of normal liver function、over the limit of normal renal function and blood sugar、abnormal cardiac troponins、obvious abnormity in the thyroid function Treatment with MECT or rTMS in nearly three months. Treatment with a systematic psychological treatment in nearly three months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bear bile pill<br>Patients randomized to the bear bile pill arm will receive treatment with 15 pills, three times daily of bear bile pill (1350mg per day) plus on-going antidepressant therapy (SSRI/SNRI). | Drug: bear bile pill<br>* Bear bile pill (15 pills) taken orally three times a day after meals with water.<br>|
| Placebo Comparator: placebo<br>Patients randomized to the placebo arm will receive 15 pills, three times daily of placebo plus on-going antidepressant therapy (SSRI/SNRI). | Drug: placebo<br>* Placebo(15 pills) taken orally three times a day after meals with water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the total Montgomery-Asberg Depression Rating Scale (MADRS) score between randomization and end of study. | The main objective is to explore whether bear bile pill add on SSRI or SNRI will improve the MDD symptoms after 8 weeks of treatment, and investigators assess the scale at baseline and week 1, 2, 4, 8. | assessed from baseline to week 8(end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective treatment | effectivity：MADRS or HAMD reduction ratio ≥50% reductive ratio: [（Baseline score- Endpoint score）／Baseline score]×100% | assessed from baseline to week 8 (end of study) | 
| Clinical remission rate | patients who are in remission at the end of the study will be summarized by treatment group, MADRS score ≤12 or HAMD-17≤7. | assessed from baseline to week 8 (end of study) | 
| The Montgomery-Asberg Depression Rating Scale (MADRS) reduction ratio | MADRS reduction ratio were used to evaluate the effectiveness of the treatment,and investigators assess the scale at baseline and week 1, 2, 4, 8. | assessed from baseline to week 8 (end of study) | 
| The Hamilton Depression Rating Scale (HAM-D17) reduction ratio | the Hamilton Depression Rating Scale reduction ratio were used to evaluate the effectiveness of the treatment,and investigators assess the scale at baseline and week 1, 2, 4, 8. | assessed from baseline to week 8 (end of study) | 
| change in the total score of the Hamilton Anxiety Scale(HAMA) |  | assessed from baseline to week 8 (end of study) | 
| change in total score of the Clinical Global Impression-Severity (CGI-S) scale. |  | assessed from baseline to week 8 (end of study) | 
| change in total score of the Clinical Global Impression-Improvement (CGI-I) scale. |  | assessed from baseline to week 8 (end of study) |