Efficacy and Safety of HQGZWWT Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling, pain, and synovial damage. Effective methods lack in the treatment of RA. A traditional prescription in use for thousands of years in China, Huang Qi Gui Zhi Wu Wu Tang(HQGZWWT)granule is still chosen to relive pain and prevent joint malformation in RA patients. However, no evidence-based medical research has been organized to assess the effectiveness and safety of HQGZWWT granules for RA.

Detailed Description
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Investigators will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether HQGZWWT granules can relieve pain and protect joints. Investigators will randomly divide 120 patients with active arthritis for 3 months. Main measurements include ratio of 50 of ACR (American College of Rheumatology), change of DAS (28) from baseline to 3 months, and SHARP scores of van der Heijde from baseline to 12 months. SecondarymeasurementsincludeACR20, ACR70, Health Assessment Questionnaire-Disability Index (HAQ-DI), arthritis pain score, and Patient Global Assessment of Arthritis. The time points are set as baseline, 2 weeks, 1 month, 2 months, 3 months, 6 months and 12 months. In addition, the rate of change (score) in the ACR50 and DAS28 from the baseline to 2-week, 1-month, 2-month, 6-month, and 12-month follow-up are also the secondary outcome measures.

Official Title
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A Multicenter, Randomized, Double-blind,Placebo-controlled Trial Evaluating the Efficacy and Safety of Huang Qi GuiZhi Wu Wu Tang Granulesin Patients With Rheumatoid Arthritis

Conditions
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Huang Qi Gui Zhi Wu Wu Granule, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Huang qi gui zhi wu wu granule
* Drug: Huang qi gui zhi wu wu granule placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with rheumatoid arthritis (score more then 5 of ACR (American College Of Rheumatology) /EULAR (European League Against Rheumatism), 2009 ) moderate-to-severe disease activity (Disease Activity Score for 28-joint counts (DAS28) of more than 3.2 an onset of symptoms within 12 months before enrollment, no prior exposure to more than 10mg oral glucocorticoids or biologic agents paid employment or unpaid but measurable work (e.g. caring for a family and home) Exclusion Criteria: combined with other disease such as adjuvant arthritis, lupus arthritis, osteoarthritis and et al. abnormal liver and my kidney function pregnancy or have a plan of pregnancy,breast feeding women severe chronic or acute disease interfering with therapy attendance alcohol or substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 group<br>Patients are given HQGZWWT granules (orally twice a day for 3 months and instructed to dissolve one package (4 g) with hot water (200 mg). | Drug: Huang qi gui zhi wu wu granule<br>* Patients are given HQGZWWT granules (orally twice a day for 3 months and instructed to dissolve one package (4 g) with hot water (200 mg)<br>|
| Placebo Comparator: Placebo group<br>Patients are given HQGZWWT granules placebo (orally twice a day for 3 months and instructed to dissolve one package (4 g) with hot water (200 mg). | Drug: Huang qi gui zhi wu wu granule placebo<br>* Patients are given HQGZWWT granules placebo (orally twice a day for 3 months and instructed to dissolve one package (4 g) with hot water (200 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 3 months | 
| changes of The Disease Activity Score (DAS) 28 | The DAS28 is an index calculating the number of painful and swollen joints (28 joints, i.e. shoulders, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints, and knees), erythrocyte sedimentation rate and the score of global assessment. The formula of DAS 28 is 0.56×√(28 painful joint count) + 0.28×√(28 swollen joint count) + 0.70× (ln ESR) + 0.014 ×GH. ESR refers to erythrocyte sedimentation rate. GH is the patient's general health visual analog scale (0-10 mm) | from baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of The Disease Activity Score (DAS) 28 | The DAS28 is an index calculating the number of painful and swollen joints (28 joints, i.e. shoulders, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints, and knees), erythrocyte sedimentation rate and the score of global assessment. The formula of DAS 28 is 0.56×√(28 painful joint count) + 0.28×√(28 swollen joint count) + 0.70× (ln ESR) + 0.014 ×GH. ESR refers to erythrocyte sedimentation rate. GH is the patient's general health visual analog scale (0-10 mm) | from baseline to 2 weeks | 
| changes of The Disease Activity Score (DAS) 28 | The DAS28 is an index calculating the number of painful and swollen joints (28 joints, i.e. shoulders, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints, and knees), erythrocyte sedimentation rate and the score of global assessment. The formula of DAS 28 is 0.56×√(28 painful joint count) + 0.28×√(28 swollen joint count) + 0.70× (ln ESR) + 0.014 ×GH. ESR refers to erythrocyte sedimentation rate. GH is the patient's general health visual analog scale (0-10 mm) | from baseline to 1 month | 
| changes of The Disease Activity Score (DAS) 28 | The DAS28 is an index calculating the number of painful and swollen joints (28 joints, i.e. shoulders, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints, and knees), erythrocyte sedimentation rate and the score of global assessment. The formula of DAS 28 is 0.56×√(28 painful joint count) + 0.28×√(28 swollen joint count) + 0.70× (ln ESR) + 0.014 ×GH. ESR refers to erythrocyte sedimentation rate. GH is the patient's general health visual analog scale (0-10 mm) | from baseline to 6 months | 
| changes of The Disease Activity Score (DAS) 28 | The DAS28 is an index calculating the number of painful and swollen joints (28 joints, i.e. shoulders, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints, and knees), erythrocyte sedimentation rate and the score of global assessment. The formula of DAS 28 is 0.56×√(28 painful joint count) + 0.28×√(28 swollen joint count) + 0.70× (ln ESR) + 0.014 ×GH. ESR refers to erythrocyte sedimentation rate. GH is the patient's general health visual analog scale (0-10 mm) | from baseline to 12 months | 
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 2 weeks | 
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 1 month | 
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 2 months | 
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 6 months | 
| Rate of ACR (American College of Rheumatology) 50 | ACR (American College of Rheumatology) 50 is a standard to describe RA symptoms. ACR 50 is met when the number of tender joints reduces by ≥50%, the number of swollen joints by ≥50%, and at least 3 of the following 5 indexes improves by ≥50%: Patient's assessment on arthritis pain using a visual analogue scale (VAS) of 0-100 mm, Patient global assessment on disease activity using VAS scale (0-10), Patient's assessment on physical function and disability (Health Assessment Questionnaire - Disability Index (HAQ-DI)), Acute phase reactant value, such as erythrocyte sedimentation rate (ESR) or C-reactive Protein (CRP) level | at 12 months | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 2 weeks | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 1 month | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 2 months | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 3 months | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 6 months | 
| change score of Health Assessment Questionnaire - Disability Index | The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. 0 refers to no functional difficulty, 1 to a bit of functional difficulty, 2 to very much functional difficulty, and 3 to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability | from baseline to 12 months | 
| change score of Patient Assessment of Arthritis Pain |  | from baseline to 2 weeks | 
| change score of Patient Assessment of Arthritis Pain | VAS score, the range is 0-10, more pain then bigger number | from baseline to 1 month | 
| change score of Patient Assessment of Arthritis Pain | VAS score, the range is 0-10, more pain then bigger number | from baseline to 2 months | 
| change score of Patient Assessment of Arthritis Pain | VAS score, the range is 0-10, more pain then bigger number | from baseline to 3 months | 
| change score of Patient Assessment of Arthritis Pain | VAS score, the range is 0-10, more pain then bigger number | from baseline to 6 months | 
| change score of Patient Assessment of Arthritis Pain | VAS score, the range is 0-10, more pain then bigger number | from baseline to 12 months | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 2 weeks | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 1 month | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 2 months | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 3 months | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 6 months | 
| change score of Patient Global Assessment of Arthritis | the range is 0-10, more pain then bigger number | from baseline to 12 months | 
| change score of 36-item Short-Form Health Survey Questionnaire |  | from baseline to 2 weeks | 
| change score of 36-item Short-Form Health Survey Questionnaire | The SF-36 measures eight dimensions, including vitality, body function, body aches, general health perceptions, body functions, emotional function, social function and mental health. SF-36 is widely used in the evaluation of quality of life in patients with rheumatoid arthritis | from baseline to 1 month | 
| change score of 36-item Short-Form Health Survey Questionnaire | The SF-36 measures eight dimensions, including vitality, body function, body aches, general health perceptions, body functions, emotional function, social function and mental health. SF-36 is widely used in the evaluation of quality of life in patients with rheumatoid arthritis | from baseline to 2 months | 
| change score of 36-item Short-Form Health Survey Questionnaire | The SF-36 measures eight dimensions, including vitality, body function, body aches, general health perceptions, body functions, emotional function, social function and mental health. SF-36 is widely used in the evaluation of quality of life in patients with rheumatoid arthritis | from baseline to 3 months | 
| change score of 36-item Short-Form Health Survey Questionnaire | The SF-36 measures eight dimensions, including vitality, body function, body aches, general health perceptions, body functions, emotional function, social function and mental health. SF-36 is widely used in the evaluation of quality of life in patients with rheumatoid arthritis | from baseline to 6 months | 
| change score of 36-item Short-Form Health Survey Questionnaire | The SF-36 measures eight dimensions, including vitality, body function, body aches, general health perceptions, body functions, emotional function, social function and mental health. SF-36 is widely used in the evaluation of quality of life in patients with rheumatoid arthritis | from baseline to 12 months | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 2 weeks | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 1 month | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 2 months | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 3 months | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 6 months | 
| change score of AIS Sleep Scale | The Athens Insomnia Scale (AIS) can help patients quantitatively self-evaluate sleep disorders with a psychometric instrument that includes eight indicators for sleep induction, awakenings during the night, final awakening, total sleep duration, sleep quality during the night, wellbeing during the night, functioning capacity during the day time, and sleepiness during the day time. The score for each indicator ranges from 0 to 3, and the total score is 24 points. The higher the score, the worse the sleep quality, and vise versa | from baseline to 12 months | 
| rate of ACR20 |  | at 2 weeks | 
| rate of ACR20 | ACR20 is met when ≥20% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 1 month | 
| rate of ACR20 | ACR20 is met when ≥20% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 2 months | 
| rate of ACR20 | ACR20 is met when ≥20% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 3 months | 
| rate of ACR20 | ACR20 is met when ≥20% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 6 months | 
| rate of ACR20 | ACR20 is met when ≥20% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 12 months | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 2 weeks | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 1 month | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 2 months | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 3 months | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 6 months | 
| rate of ACR70 | ACR70 is met when ≥70% is achieved in the reduction of tender joint number, swollen joint number, and indexes of 3 of the 5 other measurements | at 12 months |