Back to resultsTetrandrine in the Treatment of Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Tetrandrine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, tetrandrine
Eligibility Criteria
Inclusion Criteria:
- 18-65 years old.
- fulfilled the 1987 revised American College of Rheumatology (ACR) or 2010 ACR/EULAR classification criteria for RA.
- DAS28-ESR>3.2.
- MTX 7.5-20mg/w for at least 12 weeks before screening and keep stable doses for at least 4 weeks.
- Prednisone (≤10mg/d) or equivalent dose is allowed. However, the dose should be stable for at least 4 weeks before screening and should not increase during follow-up. If glucocorticoids are not used before screening, short- and intermediate-acting glucocorticoids should have been stopped at least 1 week and long-acting glucocorticoids should have been stopped at least 2 weeks.
Exclusion Criteria:
- Allergic to the drugs involved in the study, or allergic to more than two kinds of food or drugs or pollen.
- Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase.
- Any history or complication of other autoimmune diseases other than Sjogren's syndrome or Hashimoto Thyroiditis.
- Current active infections.
- Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis C virus antibody (HCV antibody), or history of AIDs.
- Females of childbearing or breastfeeding.
- Presence of any unstable cardiovascular disease (including congestive heart failure with NYHA class III or IV, unstable angina pectoris, history of myocardial infarction within one year), and the presence of conditions that can lead to QTc prolongation or arrhythmia.
- Presence of progressive, uncontrolled cerebrovascular disease, hematopoietic, endocrine (including diabetes), respiratory (including interstitial pneumonia and pulmonary fibrosis) and other serious diseases and psychiatric diseases, or the investigator believes that participation in the study would place the subject at unacceptable risk.
- History of malignancy.
- Laboratory tests during screening：i. WBC<3.5×109/L，PLT<90×109/L， Hb<90g/L; ii. ALT or AST>1.5ULN; iii. Scr>ULN.
- Use of iguratimod or disease-modifying antirheumatic drugs (DMARDs) other than MTX (such as leflunomide, sulfasalazine, hydroxychloroquine, D- penicillamine, azathioprine, cyclosporine, cyclophosphamide, Tripterygium, etc.) within 4 weeks before enrollment.
- Use of traditional Chinese medicines for rheumatoid arthritis within 4 weeks before enrollment.
- Use of b/tsDMARDs within 12 weeks.
- History of alcohol and drug abuse.
- The investigator or subinvestigator would compromise the participant's ability to safely complete the study.
- Participate in other clinical trial within 3 months prior to screening.
Sites / Locations
- Peking University People's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
tetrandrine
placebo
Arm Description
tetrandrine administered 40milligram (mg) orally thrice daily through Week 24.
Placebo administered orally thrice daily through Week 12. Starting at Week 12, participants were given tetrandrine 40 milligram (mg) orally thrice daily through Week 24.
Outcomes
Primary Outcome Measures
Proportion of Participants Achieving American College of Rheumatology (ACR) 20
The ACR20 was achieved if there was at least a 20% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Secondary Outcome Measures
Proportion of Participants Achieving American College of Rheumatology (ACR) 20
The ACR20 was achieved if there was at least a 20% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Proportion of Participants Achieving American College of Rheumatology (ACR) 50 and ACR70
The ACR50 or ACR70 was achieved if there was at least a 50% or 70% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Rates of European League Against Rheumatism (EULAR) Response Using DAS28-CRP
The Disease Activity Score Based on 28-joints Count based EULAR response criteria was used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28-CRP <=3.2; moderate responders: change from baseline >1.2 with DAS28-CRP >3.2 to <=5.1 or change from baseline >0.6 to <=1.2 with DAS28-CRP <=5.1; non-responders: change from baseline <=0.6 or change from baseline >0.6 and <=1.2 with DAS28-CRP >5.1.
Change From Baseline in Disease Activity Score 28 (DAS28)-CRP
The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and CRP value. A positive change in score indicates worsening, and a negative change indicates improvement.
Change From Baseline in Pain VAS Score
Pain assessments are reported by placing a mark on a 100 millimeter horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 represented maximum pain).
Change From Baseline in C-reactive Protein (CRP) Values
CRP (milligrams per deciliter) are blood tests.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
The degree of disability was self-evaluated by the participant using the HAQ-DI. The minimum value is 0, and the maximum values is 3. Higher scores mean a worse outcome.
Change From Baseline to Week 24 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema.
Bone edema was assessed at 25 locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. The maximum score per hand/wrist was 75 (range 0-75). Increasing score indicates greater severity.
Change From Baseline in immune cells
The percentages of immune cells, such as T/B/NK and Th subsets will be detected.
Change From Baseline in Simplified Disease Activity Index (SDAI) Score
The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. A positive change in score indicates worsening, and a negative change indicates improvement.
Change From Baseline in Clinical Disease Activity Index (CDAI) Score
The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score. A positive change in score indicates worsening, and a negative change indicates improvement.
Full Information
NCT ID
NCT05245448
First Posted
January 22, 2022
Last Updated
February 4, 2022
Sponsor
Peking University People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05245448
Brief Title
Tetrandrine in the Treatment of Rheumatoid Arthritis
Official Title
Comparing the Efficacy of Tetrandrine Combined With Methotrexate and Methotrexate Alone in the Treatment of Rheumatoid arthritis---a Randomized, Double-blinded, Placebo-controlled, Multicenter Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 22, 2022 (Anticipated)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of tetrandrine, compared with placebo in 12 week or 24 week in RA patients with inadequate response to methotrexate.
Detailed Description
The investigators designed a randomized, double-blinded, placebo-controlled, multicenter study. Adults with active rheumatoid arthritis and inadequate response to methotrexate will be enrolled, meeting the 1987 revised American College of Rheumatology (ACR) or 2010 ACR & European alliance of associations for rheumatology (EULAR) classification criteria. Two hundred forty patients at 18 to 65 years of age will be enrolled in the study, and be randomly assigned (in a 1:1 ratio) to one of the two arms (group1: tetrandrine 40mg tid for 24 weeks or group 2: placebo two tablets tid for 12 weeks, and then 40mg tid for 12 weeks). Follow-up visits will occur on weeks 4, 12 and 24. The end points were 20% improvement in American College of Rheumatology criteria (ACR20) in 12 week.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
rheumatoid arthritis, tetrandrine
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
tetrandrine
Arm Type
Experimental
Arm Description
tetrandrine administered 40milligram (mg) orally thrice daily through Week 24.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered orally thrice daily through Week 12. Starting at Week 12, participants were given tetrandrine 40 milligram (mg) orally thrice daily through Week 24.
Intervention Type
Drug
Intervention Name(s)
Tetrandrine
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Proportion of Participants Achieving American College of Rheumatology (ACR) 20
Description
The ACR20 was achieved if there was at least a 20% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Time Frame
week 12
Secondary Outcome Measure Information:
Title
Proportion of Participants Achieving American College of Rheumatology (ACR) 20
Description
The ACR20 was achieved if there was at least a 20% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Time Frame
week 4 and week 24
Title
Proportion of Participants Achieving American College of Rheumatology (ACR) 50 and ACR70
Description
The ACR50 or ACR70 was achieved if there was at least a 50% or 70% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP.
Time Frame
week 12 and week 24
Title
Rates of European League Against Rheumatism (EULAR) Response Using DAS28-CRP
Description
The Disease Activity Score Based on 28-joints Count based EULAR response criteria was used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28-CRP <=3.2; moderate responders: change from baseline >1.2 with DAS28-CRP >3.2 to <=5.1 or change from baseline >0.6 to <=1.2 with DAS28-CRP <=5.1; non-responders: change from baseline <=0.6 or change from baseline >0.6 and <=1.2 with DAS28-CRP >5.1.
Time Frame
week 12 and week 24
Title
Change From Baseline in Disease Activity Score 28 (DAS28)-CRP
Description
The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and CRP value. A positive change in score indicates worsening, and a negative change indicates improvement.
Time Frame
Baseline, week 4, week 12 and week 24
Title
Change From Baseline in Pain VAS Score
Description
Pain assessments are reported by placing a mark on a 100 millimeter horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 represented maximum pain).
Time Frame
Baseline, week 4, week 12 and week 24
Title
Change From Baseline in C-reactive Protein (CRP) Values
Description
CRP (milligrams per deciliter) are blood tests.
Time Frame
Baseline, week 4, week 12 and week 24
Title
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
Description
The degree of disability was self-evaluated by the participant using the HAQ-DI. The minimum value is 0, and the maximum values is 3. Higher scores mean a worse outcome.
Time Frame
Baseline, week 4, week 12 and week 24
Title
Change From Baseline to Week 24 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema.
Description
Bone edema was assessed at 25 locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. The maximum score per hand/wrist was 75 (range 0-75). Increasing score indicates greater severity.
Time Frame
Baseline and week 12
Title
Change From Baseline in immune cells
Description
The percentages of immune cells, such as T/B/NK and Th subsets will be detected.
Time Frame
Baseline, week 12 and week 24
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) Score
Description
The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. A positive change in score indicates worsening, and a negative change indicates improvement.
Time Frame
Baseline, week 4, week 12 and week 24
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) Score
Description
The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score. A positive change in score indicates worsening, and a negative change indicates improvement.
Time Frame
Baseline, week 4, week 12 and week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18-65 years old.
fulfilled the 1987 revised American College of Rheumatology (ACR) or 2010 ACR/EULAR classification criteria for RA.
DAS28-ESR>3.2.
MTX 7.5-20mg/w for at least 12 weeks before screening and keep stable doses for at least 4 weeks.
Prednisone (≤10mg/d) or equivalent dose is allowed. However, the dose should be stable for at least 4 weeks before screening and should not increase during follow-up. If glucocorticoids are not used before screening, short- and intermediate-acting glucocorticoids should have been stopped at least 1 week and long-acting glucocorticoids should have been stopped at least 2 weeks.
Exclusion Criteria:
Allergic to the drugs involved in the study, or allergic to more than two kinds of food or drugs or pollen.
Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase.
Any history or complication of other autoimmune diseases other than Sjogren's syndrome or Hashimoto Thyroiditis.
Current active infections.
Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis C virus antibody (HCV antibody), or history of AIDs.
Females of childbearing or breastfeeding.
Presence of any unstable cardiovascular disease (including congestive heart failure with NYHA class III or IV, unstable angina pectoris, history of myocardial infarction within one year), and the presence of conditions that can lead to QTc prolongation or arrhythmia.
Presence of progressive, uncontrolled cerebrovascular disease, hematopoietic, endocrine (including diabetes), respiratory (including interstitial pneumonia and pulmonary fibrosis) and other serious diseases and psychiatric diseases, or the investigator believes that participation in the study would place the subject at unacceptable risk.
History of malignancy.
Laboratory tests during screening：i. WBC<3.5×109/L，PLT<90×109/L， Hb<90g/L; ii. ALT or AST>1.5ULN; iii. Scr>ULN.
Use of iguratimod or disease-modifying antirheumatic drugs (DMARDs) other than MTX (such as leflunomide, sulfasalazine, hydroxychloroquine, D- penicillamine, azathioprine, cyclosporine, cyclophosphamide, Tripterygium, etc.) within 4 weeks before enrollment.
Use of traditional Chinese medicines for rheumatoid arthritis within 4 weeks before enrollment.
Use of b/tsDMARDs within 12 weeks.
History of alcohol and drug abuse.
The investigator or subinvestigator would compromise the participant's ability to safely complete the study.
Participate in other clinical trial within 3 months prior to screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ru Li, MD, PhD
Phone
+86 1861161621
Email
doctorliru123@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li
Organizational Affiliation
Department of Rheumatology and Immunology, Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
ZIP/Postal Code
100044
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li, MD, PhD
Phone
+86 10 88324178
Email
li99@bjmu.edu.cn
12. IPD Sharing Statement
Learn more about this trial
Tetrandrine in the Treatment of Rheumatoid Arthritis
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