Complementary Herbal Approach to Rheumatoid Management Study (CHARMS)

NCT07627893 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025/0161
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid Arthritis (RA) is a chronic disease characterised by symmetric, polyarticular pain and swelling, involving small joints of the hands and feet. RA can lead to irreversible joint damage without treatment, causing disability and impacting daily activities and work productivity. Some patients turn to Chinese Herbal Medication (CHM) for treatment. Since there is currently no well designed randomised controlled trial to support the 'real-world' use of Si Miao Xiao Bi Tang with anti-rheumatic drugs, such as methotrexate, the investigators are conducting a 12-week, randomised double-blinded placebo-controlled trial to determine the efficacy, safety and cost effectiveness of a modified Si Miao Xiao Bi Tang, a type of CHM, in the treatment of patients with active RA.

Conditions

Rheumatoid Arthritis (RA)

Keywords

Rheumatoid Arthritis; Chinese Herbal Medicine; Traditional Chinese Medicine; Si Miao Xiao Bi

Outcome Measures

Primary Outcomes (1)

• American College of Rheumatology 20% improvement criteria (ACR20) at week 8

  To achieve an ACR20 response, a patient with RA must demonstrate a 20% improvement in both tender and swollen joint counts, and 20% improvement in at least three of the following five criteria: patient's assessment of disease activity, physician's assessment of treatment response, patient's ability to perform daily activities based on Health Assessment Questionnaire-Disability Index (HAQ-DI), pain level, and serum inflammation markers.

  Enrollment to week 8.

Secondary Outcomes (7)

• ACR20 response at week 12

  Enrollment to week 12.

• ACR50 response at weeks 8 and 12

  Enrollment to week 8, 12.

• ACR70 response at weeks 8 and 12

  Enrollment to week 8, 12.

• 28-joint disease activity score using ESR (DAS28-ESR) at weeks 8, 12.

  Enrollment to week 8, 12.

• Impact of RA on disability as measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI) at weeks 8, 12.

  Enrollment to week 8, 12.

Other Outcomes (1)

• Severity of synovitis determined using the EULAR-OMERACT ultrasound scoring system at week 8

  Enrollment to week 8.

Study Arms (2)

Intervention

EXPERIMENTAL

In addition to usual rheumatological care, patients receive take Shu Bi Ning for a period of 12 weeks.

Other: Shu Bi Ning (modified Si Miao Xiao Bi); Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

In addition to usual rheumatological care, patients receive take a Shu Bi Ning placebo for a period of 12 weeks.

Drug: Methotrexate; Other: Shu Bi Ning placebo

Interventions

Shu Bi Ning (modified Si Miao Xiao Bi) OTHER

Shu Bi Ning (modified Si Miao Xiao Bi) is a chinese herbal medication for treatment of damp-heat syndrome.

Intervention

Methotrexate DRUG

Patients receive standard dose of oral methotrexate that is ordered by their attending rheumatologist.

Intervention; Placebo

Shu Bi Ning placebo OTHER

Placebo granules will be manufactured with no new herbal components (all herbal content is HSA certified). Placebo granules will comprise of 5% of the herbal components (using Modified Si Miao Xiao Bi), 95% black bean powder and 0.05% denatonium benzoate will be added as a bitterant. This is to ensure that the placebo possesses similar taste and smell of the herbal components. The placebo will be colour adjusted to match actual herbal granules, and the packaging for the herbal and placebo granules will be done using the same packaging material to ensure both are similar in appearance.

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients between the ages of 21 and 70 years, and diagnosed with RA by a rheumatologist and fulfilling the 2010 ACR/EULAR classification criteria for RA.
• Active disease with DAS28 ESR ≥3.2 at screening, with at least 6 swollen joints out of 66 and at least 6 tender joints out of 68.
• Receiving stable doses of methotrexate therapy for at least 3 months, and on stable dose for at least 4 weeks before trial entry ( ≥10mg per week), either subcutaneous or orally.
• Stable doses of non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, or oral corticosteroids (equivalent to prednisone ≤ 10 mg) for at least 4 weeks prior to first dose of study medication.
• Except for methotrexate, patients must have discontinued all csDMARDs, including, but not limited to: hydroxychloroquine, sulfasalazine, leflunomide prior to first dose of study medication as specified below:
• ≥ 4 weeks prior to Baseline Visit for sulfasalazine and hydroxychloroquine
• ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure (i.e., 11 days with cholestyramine, or 30 days washout with activated charcoal)
• A negative urine pregnancy test for women of childbearing potential on Day 1 (prior to administration of first dose of study drug).
• Use of a reliable method of contraception by all female patients of childbearing potential and male patients with procreative capacity during the study and up to 3 months after the last dose of the study medication.

You may not qualify if:

• Not able to provide informed consent.
• Previous lack of efficacy to Si Miao Xiao Bi Tang.
• History of inflammatory joint disease other than RA. Secondary Sjogren's Syndrome is permitted.
• Concurrent use of other immunosuppressant medications, except MTX and protocol allowed doses of steroids.
• Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point administration of corticosteroids in the preceding 4 weeks prior to the Baseline Visit.
• Subject has been treated with any investigational drug within a minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the Baseline Visit or is currently enrolling in another clinical study.
• Pregnant or breastfeeding females.
• Infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses, untreated malignancy, or evidence of active or untreated latent tuberculosis.
• Receipt of any live vaccine within 1 month prior to the Screening Visit, or expected need of live vaccination during study participation including up to 1 month after the last dose of study drug.
• History of clinically significant hematologic, pulmonary, renal, hepatic, or psychiatric disease that would interfere with the subject's participation in this study.
• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Day 1 or oral anti-infectives within 14 days prior to the Baseline Visit.
• Any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
• Evidence of hematopoietic disorder or hemoglobin \<9 g/dL
• White blood cell count \<3.0 x 10\^9/L (\<3000/mm\^3)
• Absolute neutrophil count \<1.2 x 10\^9/L (\<1000/mm\^3)

Sponsors & Collaborators

• Singapore General Hospital: lead
• Thong Chai Institute of Medical Research: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Warren Fong

CONTACT

+65 63214028; warren.fong.w.s@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: June 4, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)