Complementary Herbal Approach to Rheumatoid Management Study (CHARMS)
ConditionRheumatoid Arthritis (RA)
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age21-70
SponsorSingapore General Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Shu Bi Ning (modified Si Miao Xiao Bi)
Other interventionShu Bi Ning (modified Si Miao Xiao Bi) is a chinese herbal medication for treatment of damp-heat syndrome.
Methotrexate
DrugPatients receive standard dose of oral methotrexate that is ordered by their attending rheumatologist.
Shu Bi Ning placebo
Other interventionPlacebo 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.
Treatment groups
132 Participants
are divided into 2 treatment groupsGroup A: InterventionExperimental treatment 2 interventions
Group B: PlaceboPlacebo comparator 2 interventions
Trial outcomes
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.
Time frame
Enrollment to week 8.Secondary outcomes
1
ACR20 response at week 12
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.
Time frame
Enrollment to week 12.2
ACR50 response at weeks 8 and 12
To achieve an ACR50 response, a patient with RA must demonstrate a 50% improvement in both tender and swollen joint counts, and 50% 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.
Time frame
Enrollment to week 8, 12.3
ACR70 response at weeks 8 and 12
To achieve an ACR70 response, a patient with RA must demonstrate a 70% improvement in both tender and swollen joint counts, and 70% 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.
Time frame
Enrollment to week 8, 12.4
28-joint disease activity score using ESR (DAS28-ESR) at weeks 8, 12.
The DAS28-ESR is a composite measure used to evaluate disease activity in RA. It incorporates four components: the tender joint count (TJC) and swollen joint count (SJC) out of 28 specified joints, the patient's global health assessment using a visual analog scale (VAS), and the erythrocyte sedimentation rate (ESR), which is a marker of inflammation. The score ranges from 0 to 9.4, with thresholds defining remission (\<2.6), low disease activity (2.6-3.2), moderate disease activity (\>3.2-5.1), and high disease activity (\>5.1).
Time frame
Enrollment to week 8, 12.Other outcomes
1
Severity of synovitis determined using the EULAR-OMERACT ultrasound scoring system at week 8
The EULAR-OMERACT ultrasound scoring is a standardized method for assessing synovitis, combining synovial hypertrophy (B-mode) and power Doppler signal (using semiquantitative scales from 0-3) to evaluate inflammation, developed collaboratively by the European League Against Rheumatism (EULAR) and the Outcome Measures in Rheumatology (OMERACT) group. Higher scores indicate more severe inflammation.
Time frame
Enrollment to week 8.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Singapore General Hospital
Lead sponsor
Thong Chai Institute of Medical Research
Collaborator
Source ClinicalTrials.gov