Efficacy of Shinabro in Hand Osteoarthritis

Treatment Efficacy of 'Shinbaro Capsule' in the Treatment of Hand Osteoarthritis: Randomized, Double-blinded, Placebo-controlled, Multicenter Investigator Initiated Trial.

GCSB-5 ("Shinbaro capsule"), is a mixture of 6 oriental herbs that have anti-inflammatory and analgesic effects along with an excellent safety profile. This study is aimed at investigating efficacy of Shinbaro in the treatment of hand osteoarthritis which needs a long term treatment in a placebo controlled, double-blind randomized trial.

Study Overview

• Status: Completed
• Conditions: Hand Osteoarthritis
• Intervention / Treatment: Drug: Placebo; Drug: Shinbaro

Detailed Description

Osteoarthritis (OA) as a common musculoskeletal disease affects more than 30% of the elderly population. It frequently involves knees, hips, spines and hands. In hands, the distal and proximal interphalangeal and the first carpometacarpal joints are affected, leading often to significant disability and limitation in the daily activity. The chronic progressive nature of the disease requires a life-long treatment. The mainstay treatment of hand OA targets pain control. Non-steroidal anti-inflammatory drugs (NSAIDs) are often used. However, they are frequently associated with significant gastrointestinal side effects including gastritis, peptic ulcer diseases, and bleeding, especially with long term use. Further, they do not ameliorate pain completely, requiring additional medications such as acetaminophen or opioid-based analgesics.

Shibaro is a mixture of purified oriental herbs consisting of Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex. These herbs have been used for the treatment of diverse inflammatory conditions in Chines traditional medicine. All 6 herbs show an excellent safety profile and their anti-inflammatory and analgesic effects have been studied in both animals and humans. As such, given the excellent safety profile, anti-inflammatory and analgesic effects, Shinbaro might be ideal in the treatment of OA.

This study will investigate the efficacy and safety of Shinbaro in the treatment of hand OA in a placebo-controlled, randomized, double-blind, multi-center trial.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Gyeonggi-do
    • Bundang, Gyeonggi-do, Korea, Republic of, 463-870
      • Seoul National Univ. Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 40 years or older
• Osteoarthritis according to ACR 1990 criteria
• Mean joint visual analog pain score (VAS) > 30mm in the preceding 48 hours
• Patients who are will to participate

Exclusion Criteria:

• Any prior surgery of hand joints
• prior history of Shinbaro use
• Intra-articular injection of glucocorticosteroid or hyaluronic acid in the preceding 3 months
• Pregnancy or active breast feeding
• Prior hypersensitivity reaction to herbal medications
• AST or ALT elevation > 3 of upper normal limit
• GRF (MDRD) < 30 mg/min/1.73m2
• Nephrotic syndrome, other signficant kidney disease
• Patients who seem not to tolerate the study at investigator's discretion
• Patients who refuse to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo 2 capsules, twice daily, for 12 weeks.	Drug: Placebo; The study medication and placebo were identical in appearance.
ACTIVE_COMPARATOR: Shinbaro; Shinbaro, 2 capsules (300mg), twice daily, for 12 weeks	Drug: Shinbaro; GCSB-5 (Shinbaro) is a mixture of six purified oriental herb extracts in a fixed ratio, namely, Saposhnikovia divaricata Schischk, Glycine max Merrill, Cibotium barometz J. Smith, Eucommia ulmoides Oliver, Achyranthes japonica Nakai, and Acanthopanax sessiliflorus Seem; Other Names: GCSB-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUSCAN Pain Change at 4 Weeks From Baseline	Change in AUSCAN pain score at 4 weeks from baseline = Pain at 4 weeks (0-100) - Pain at baseline (0-100). AUSCAN Pain scale ranges from 0 (no pain) to 100 (worst possible pain).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUSCAN Pain Score at 8 Weeks From Baseline	Change in AUSCAN pain score at 8 weeks from baseline = Pain at 8 weeks (0-100)- Pain at baseline (0-100). AUSCAN Pain scale ranges from 0 (no pain) to 100 (worst possible pain).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline, 8 weeks
AUSCAN Pain Score at 12 Weeks From Baseline	Change in AUSCAN pain score at 12 weeks from baseline = Pain at 12 weeks (0-100)- Pain at baseline (0-100). AUSCAN Pain scale ranges from 0 (no pain) to 100 (worst possible pain).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline, 12 weeks
AUSCAN Pain Score at 16 Weeks From Baseline	Change in AUSCAN pain score at 16 weeks from baseline = Pain at 16 weeks (0-100)- Pain at baseline (0-100). AUSCAN Pain scale ranges from 0 (no pain) to 100 (worst possible pain).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
AUSCAN Stiffness at 4 Weeks Change From Baseline	Change in AUSCAN stiffness score at 4 weeks from baseline = Stiffness at 4 weeks (0-100)- Stiffness at baseline (0-100). AUSCAN Stiffness scale ranges from 0 (no stiffness) to 100 (worst possible stiffness).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 4 weeks
AUSCAN Stiffness at 8 Weeks Change From Baseline	Change in AUSCAN stiffness score at 8 weeks from baseline = Stiffness at 8 weeks (0-100)- Stiffness at baseline (0-100). AUSCAN Stiffness scale ranges from 0 (no stiffness) to 100 (worst possible stiffness).; Negative value means improvement from baseline; Positive value means deterioration from baseline	baseline and 8 weeks
AUSCAN Stiffness at 12 Weeks Change From Baseline	Change in AUSCAN stiffness score at 12 weeks from baseline = Stiffness at 12 weeks (0-100)- Stiffness at baseline (0-100). AUSCAN Stiffness scale ranges from 0 (no stiffness) to 100 (worst possible stiffness).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Basline and 12 weeks
AUSCAN Stiffness at 16 Weeks Change From Baseline	Change in AUSCAN stiffness score at 16 weeks from baseline = Stiffness at 16 weeks (0-100)- Stiffness at baseline (0-100). AUSCAN Stiffness scale ranges from 0 (no stiffness) to 100 (worst possible stiffness).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline, 16 weeks
AUSCAN Function Change at 4 Weeks From Baseline	Change in AUSCAN function score at 4 weeks from baseline = Function score at 4 weeks (0-100)- Function score at baseline (0-100). AUSCAN Function score scale ranges from 0 (no functional limitation) to 100 (worst possible functional limitation).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Basline and 4 weeks
AUSCAN Function Change at 8 Weeks From Baseline	Change in AUSCAN function score at 8 weeks from baseline = Function score at 8 weeks (0-100)- Function score at baseline (0-100). AUSCAN Function score scale ranges from 0 (no functional limitation) to 100 (worst possible functional limitation).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 8 weeks
AUSCAN Function Change at 12 Weeks From Baseline	Change in AUSCAN function score at 12 weeks from baseline = Function score at 12 weeks (0-100)- Function score at baseline (0-100). AUSCAN Function score scale ranges from 0 (no functional limitation) to 100 (worst possible functional limitation).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 12 weeks
AUSCAN Function Change at 16 Weeks From Baseline	Change in AUSCAN function score at 16 weeks from baseline = Function score at 16 weeks (0-100)- Function score at baseline (0-100). AUSCAN Function score scale ranges from 0 (no functional limitation) to 100 (worst possible functional limitation).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
Patient Global Assessment, Change From Baseline	Change in Patient global assessment (PGA) at 4 weeks from baseline = PGA at 4 weeks (0-100)- PGA score at baseline (0-100). PGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 4 weeks
Patient Global Assessment, Change From Baseline	Change in Patient global assessment (PGA) at 8 weeks from baseline = PGA at 8 weeks (0-100)- PGA score at baseline (0-100). PGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 8 weeks
Patient Global Assessment, Change From Baseline	Change in Patient global assessment (PGA) at 12 weeks from baseline = PGA at 12 weeks (0-100)- PGA score at baseline (0-100). GPA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 12 weeks
Patient Global Assessment, Change From Baseline	Change in Patient global assessment (PGA) at 16 weeks from baseline = PGA at 16 weeks (0-100)- PGA score at baseline (0-100). PGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
Physician Global Assessment, Change From Baseline	Change in Physician global assessment (PhGA) at 4 weeks from baseline = PhGA at 4 weeks (0-100)- PhGA score at baseline (0-100). GPA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	baseline and 4 weeks
Physician Global Assessment, Change From Baseline	Change in Physician global assessment (PhGA) at 8 weeks from baseline = PhGA at 8 weeks (0-100)- PhGA score at baseline (0-100). PhGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 8 weeks
Physician Global Assessment, Change From Baseline	Change in Physician global assessment (PhGA) at 12 weeks from baseline = PhGA at 12 weeks (0-100)- PhGA score at baseline (0-100). PhGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 12 weeks
Physician Global Assessment, Change From Baseline	Change in Physician global assessment (PhGA) at 16 weeks from baseline = PhGA at 16 weeks (0-100)- PhGA score at baseline (0-100). PhGA scale ranges from 0 (excellent condition) to 100 (worst possible worse possible condition).; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
Tender Joint Count, Change From Baseline	Change in Tender joint count (TJC) at 4 weeks from baseline = TJC at 4 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 4 weeks
Tender Joint Count, Change From Baseline	Change in Tender joint count (TJC) at 8 weeks from baseline = TJC at 8 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 8 weeks
Tender Joint Count, Change From Baseline	Change in Tender joint count (TJC) at 12 weeks from baseline = TJC at 12 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 12 weeks
Tender Joint Count, Change From Baseline	Change in Tender joint count (TJC) at 16 weeks from baseline = TJC at 16 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
Swollen Joint Count, Change From Baseline	Change in Swollen joint count (SJC) at 4 weeks from baseline = SJC at 4 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 4 weeks
Swollen Joint Count, Change From Baseline	Change in Swollen joint count (SJC) at 8 weeks from baseline = SJC at 8 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 8 weeks
Swollen Joint Count, Change From Baseline	Change in Swollen joint count (SJC) at 12 weeks from baseline = SJC at 12 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 12 weeks
Swollen Joint Count, Change From Baseline	Change in Swollen joint count (SJC) at 16 weeks from baseline = SJC at 16 weeks - TJC at baseline..; Negative value means improvement from baseline; Positive value means deterioration from baseline	Baseline and 16 weeks
Acetaminophen Rescue	yes = AAP rescue use, no = no AAP rescue use	Baseline 4 weeks
Acetaminophen Rescue	yes = AAP rescue use, no = no AAP rescue use	4 weeks and 8 weeks
Acetaminophen Rescue	yes = AAP rescue use, no = no AAP rescue use	8 weeks and 12 weeks
Acetaminophen Rescue	yes = AAP rescue use, no = no AAP rescue use	12 weeks and 16 weeks
Number of OMERACT-OARSI Responder	Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Number of patients who met OMERACT-OARSI criteria = significant clinical improvement in osteoarthritis symptom after treatment	Baseline and 4 weeks
Number of OMERACT-OARSI Responder	Number of patients who met OMERACT-OARSI criteria = significant clinical improvement in osteoarthritis symptom after treatment	Baseline and 8 weeks
Number of OMERACT-OARSI Responder	Number of patients who met OMERACT-OARSI criteria = significant clinical improvement in osteoarthritis symptom after treatment	Baseline and 12 weeks
Number of OMERACT-OARSI Responder	Number of patients who met OMERACT-OARSI criteria = significant clinical improvement in osteoarthritis symptom after treatment	Baselie and 16 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Green Cross Corporation
• Investigators: Study Director: Yun Jong Lee, MD PhD, Seoul National Universty Bundang Hospital; Study Director: Kichul Shin, MD PhD, SMG-SNU Boramae Medical Center

Publications and helpful links

General Publications

• Kloppenburg M. Hand osteoarthritis-nonpharmacological and pharmacological treatments. Nat Rev Rheumatol. 2014 Apr;10(4):242-51. doi: 10.1038/nrrheum.2013.214. Epub 2014 Jan 28.
• Shin K, Kim JW, Moon KW, Yang JA, Lee EY, Song YW, Lee EB. The efficacy of diacerein in hand osteoarthritis: a double-blind, randomized, placebo-controlled study. Clin Ther. 2013 Apr;35(4):431-9. doi: 10.1016/j.clinthera.2013.02.009. Epub 2013 Mar 6.
• Kim JK, Park SW, Kang JW, Kim YJ, Lee SY, Shin J, Lee S, Lee SM. Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced Osteoarthritis in Rats. Evid Based Complement Alternat Med. 2012;2012:730907. doi: 10.1155/2012/730907. Epub 2012 Mar 4.
• Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, Simon L, Strand V, Woodworth T, Dougados M. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004 May;12(5):389-99. doi: 10.1016/j.joca.2004.02.001.
• Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.
• Park YG, Ha CW, Han CD, Bin SI, Kim HC, Jung YB, Lim HC. A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint. J Ethnopharmacol. 2013 Oct 7;149(3):816-24. doi: 10.1016/j.jep.2013.08.008. Epub 2013 Aug 14.
• Coxib and traditional NSAID Trialists' (CNT) Collaboration; Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013 Aug 31;382(9894):769-79. doi: 10.1016/S0140-6736(13)60900-9. Epub 2013 May 30.
• Park JK, Shin K, Kang EH, Ha YJ, Lee YJ, Lee KH, Lee EY, Song YW, Choi Y, Lee EB. Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial. Clin Ther. 2016 Aug;38(8):1858-1868.e2. doi: 10.1016/j.clinthera.2016.06.016. Epub 2016 Jul 21.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (ESTIMATE): July 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 17, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: osteoarthritis; hand; Shinbaro; GCSB-5
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: GC6102F