Randomized Clinical Trial of Shugan Jieyu Capsule in Generalized Anxiety Disorder

Study Overview
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Brief Summary
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This trial was a multi-center, randomized, double-blind, two-stage clinical trial in patients with generalized anxiety disorder (TCM differentiated as liver Qi stagnation and spleen deficiency syndrome), consisting of a exploratory study(stage 1) and a confirmatory study(stage 2). In stage 1, 120 subjects were enrolled and randomly assigned to high-dose group, low-dose group and placebo group at a ratio of 1:1:1. In stage 2, 440 subjects (final sample size was re-estimated based on the results of stage 1) were randomly assigned to the experimental and placebo groups at a ratio of 1:1.

Official Title
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A Multi-center, Randomized, Double-Blind Clinical Trial of Shugan Jieyu Capsule in Generalized Anxiety Disorder

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: Shugan Jieyu Capsules
* Drug: Shugan Jieyu Capsules+Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of generalized anxiety disorder (GAD) as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as confirmed by the MINI at Screening, The duration of illness must be ≥ 6 months； Age 18-65 years old； Hamilton Anxiety Rating Scale (HAM-A) Total Score of ≥ 14 at both Screening and Baseline，Anxious Mood (item 1) score ≥2； Clinical Global Impression of Severity Scale (CGI-S) score of ≥ 3 at both Screening and Baseline The TCM syndrome is liver Qi stagnation and spleen deficiency syndrome. Exclusion Criteria: Diagnosed with a psychiatric disorder other than GAD that meets DSM-5 criteria within 6 months prior to screening； Alcohol or drug abuse or dependence in the 6 months prior to screening, or urine positive for multiple drugs combined at screening Hamilton Depression Rating Scale (HAMD-17) Total Score of > 17 at Screening or Baseline，or Depressive Mood (item 1) score ≥2； Patients with Severe Insomnia.

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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No

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: Experimental: Shugan Jieyu Capsules<br>Participants received Shugan Jieyu Capsules 4 capsules,BID,once in the morning and once in the evening, at an interval of more than 8 hours, for up tp 12 weeks. | Drug: Shugan Jieyu Capsules<br>* Oral, 4 Capsules, BID<br>|
| Experimental: Experimental: Shugan Jieyu Capsules+Placepo<br>Participants received Shugan Jieyu Capsules 3 capsules + Placebo 1 capsules,BID,once in the morning and once in the evening, at an interval of more than 8 hours, for up tp 12 weeks. | Drug: Shugan Jieyu Capsules+Placebo<br>* Drug: Shugan Jieyu Capsules, Oral，3 capsules，BID Drug: Placebo, Oral, 1 capsule, BID<br>|
| Placebo Comparator: Experimental: Placebo<br>Participants received placebo 4 capsules,BID,once in the morning and once in the evening, at an interval of more than 8 hours, for up tp 12 weeks. | Drug: Placebo<br>* Oral，4 capsules，BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the HAM-A Total Score at Week 12 | The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-administered scale which consists of 14 items, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The highest possible score is 56, which represents the most severe form of anxiety; the lowest possible score is 0, which represents an absence of anxiety. | Change from Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the HAM-A Total Score at Week 2, 4, and 8 | The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-administered scale which consists of 14 items, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The highest possible score is 56, which represents the most severe form of anxiety; the lowest possible score is 0, which represents an absence of anxiety. | Change from Baseline to Week 2, 4, and 8 | 
| The Proportion of Subjects with HAM-A Total Score Reduction Rate ≥50% at week 2, 4, 8 and 12; | The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-administered scale which consists of 14 items, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The highest possible score is 56, which represents the most severe form of anxiety; the lowest possible score is 0, which represents an absence of anxiety. | Change from Baseline to Week 2, 4, 8 and 12 | 
| The Proportion of Subjects with HAM-A Total Score ≤7 at week 2, 4, 8 and 12 | The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-administered scale which consists of 14 items, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The highest possible score is 56, which represents the most severe form of anxiety; the lowest possible score is 0, which represents an absence of anxiety. | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the HAM-A Mental Anxiety Score at Week 2, 4, 8 and 12 | HAM-A Mental Anxiety Score was the sum of Items 1 to 6 and Item 14 and could have ranged from 0 to 28. | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the HAM-A Somatic Anxiety Score at Week 2, 4, 8 and 12 | The HAM-A Somatic Anxiety Factor Score was the sum of Items 7 to 13 and could have ranged from 0 to 28. | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the The World Health Organization Quality of Life (WHOQOL)-BREF at Week 2, 4, 8 and 12 | The scale evaluates the quality of life in four areas: physiology, psychology, social relations and environment. | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at Week 2, 4, 8 and 12 | The CGI-S is measures the clinician's impression of a subject's current anxiety severity considering their total clinical experience with the patient population. This measure uses a 0-7 scale, with higher scores indicating greater anxiety severity. | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the Clinical Global Impression of Improvement Scale (CGI-I) at Week 2, 4, 8 and 12 | CGI-I measured the clinician's perception of the participant's improvement at the time of assessment compared with the baseline. Scores could have ranged from 1 (very much improved) to 7 (very much worse). | Change from Baseline to Week 2, 4, 8 and 12 | 
| Change From Baseline in the Traditional Chinese Medicine Syndrome Score Scale at Week 2, 4, 8 and 12 | TCM syndrome scale was used to evaluate the changes of TCM symptoms and signs before and after treatment. | Change from Baseline to Week 2, 4, 8 and 12 |