A Phase 2/3 interventional study of Shu Bi Ning (modified Si Miao Xiao Bi) and Methotrexate in Rheumatoid Arthritis (RA), sponsored by Singapore General Hospital. Recruiting at 1 site in Singapore. Open to participants aged 21 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-08-17.
Sponsored by Singapore General Hospital · Phase 2/3, Interventional, and Treatment
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.
From the Traditional Chinese Medicine (TCM) perspective, RA is part of the Bi Syndrome. Si Miao Xiao Bi Tang is one of the formulas listed in the guidelines for treatment of Damp-Heat syndrome. Till date, few studies have explored use of CHM, in particular Si Miao Xiao Bi Tang, in treating RA. According to past systematic reviews of radnomised controlled trials performed on Chinese herbs in RA patients, most studies were of low methodological quality and small numbers, resulting in lack of generalizability. Studies looking into cost effectiveness are also lacking.
Proposed project is a randomised double-blind placebo-controlled trial to be conducted over a period of three years, anchored to the Consolidated Standards of Reporting Trials (CONSORT) guidelines and CONSORT extension for CHM. Eligible patients will be randomly allocated to receive CHM and methotrexate or methotrexate and placebo on a 1:1 basis via random permuted block randomization.
Intervention group and control group patients receive methotrexate and CHM or methotrexate and placebo respectively for 12 weeks. They will attend rheumatologist reviews at weeks 0, 4, 8, and 12, including physical exams and disease monitoring. Safety is tracked through blood tests, and further tests are ordered as needed. TCM physicians participate by counselling and diagnosing TCM syndrome and monitoring for side effects during study visits at weeks 0, 4, 8 and 12.
American College of Rheumatology 20% improvement criteria (ACR20) at week 8 is the primary outcome. 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.
Secondary outcomes include ACR20 response ACR50 response, ACR70 response, 28-joint disease activity score using ESR (DAS28-ESR), impact of RA on disability as measured using the Health Assessment Questionnaire Disability Index (HAQ-DI), severity of synovitis as determined using the EULAR-OMERACT ultrasound scoring system, quality of life as measured using the Medical Outcomes Study Short-Form (36-item) Health Survey (SF-36), fatigue level as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and safety of the trial.
Exploratory outcome is improvement in ultrasound inflammation at week 8 as compared to baseline, based on EULAR-OMERACT ultrasound scoring system.
3,332 studies on the registry are indexed under Arthritis, Rheumatoid; 443 are open to participants now.
This study's planned enrollment of 132 is above the median of 96 across 2,220 interventional studies indexed under Arthritis, Rheumatoid.
Browse Arthritis, Rheumatoid studies →Singapore General Hospital is the lead sponsor of 270 studies on the registry; 57 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Exclusion Criteria:
Any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Shu Bi Ning (modified Si Miao Xiao Bi) is a chinese herbal medication for treatment of damp-heat syndrome.
Patients receive standard dose of oral methotrexate that is ordered by their attending rheumatologist.
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.
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.
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.
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.
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.
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.
Impact of RA on disability as measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI) at weeks 8, 12.
The HAQ-DI is a self-reported measure of functional status. It consists of 20 questions across eight categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each item is scored on a scale from 0 (no difficulty) to 3 (unable to do). The overall HAQ-DI score, ranging from 0 to 3, is calculated by averaging the eight category scores, with higher scores indicating greater disability.
Time frame: Enrollment to week 8, 12.
Quality of life as measured using the Medical Outcomes Study Short-Form (36-item) Health Survey (SF-36) at week 8, 12
The SF-36 measures health-related quality of life (HRQoL). It comprises 36 questions that assesses eight health domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These domains can be further summarized into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The SF-36 uses a scoring system ranging from 0 to 100 for each domain, with higher scores indicating better health status.
Time frame: Enrollment to week 8, 12.
Fatigue level as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale at week 8, 12.
The FACIT-F is a 13-item measure designed to assess self-reported fatigue and its impact on daily activities and function. Scores range from 0 to 52, where higher scores indicate less fatigue.
Time frame: Enrollment to week 8, 12.
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.
Plan to share: No
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Started Jun 2026 (actual). Primary completion is estimated for May 2029, 35 months after the start.
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