Clinical Trial of Osteoarthritis Jamu Formula Compare to Piroxicam

Background: Indonesian herbs have several formulas which have been used traditionally to reduce pain of osteoarthritis (OA). However, there is a lack of evidence of its efficacy and safety. The objectives of study were to investigate the efficacy and safety of a traditional formula for OA. Methods: Design of the study was a randomized clinical trial (RCT) involved 123 patients (subjects) for 28 days intervention. This study was conducted between March - December 2014 with 30 physicians were participated at 20 regencies in Indonesia. The variables measured were VAS score, PGAP functional status assessment (FSA), and Short Form (SF-36) to assess jamu efficacy in comparison to piroxicam. To evaluate the safety of jamu formula using values of SGOT, SGPT, BUN, and creatinine. Result: The jamu formula administration effects can reduce VAS significantly (p<0.05) if it was compared to baseline. FSA score of jamu formula group was decreased significantly (p=0.000) when compared to the start of intervention. Short Form (SF)-36 of jamu formula group were significantly improved when compared with baseline value. The result of the three parameters between jamu group and piroxicam group should not significantly different. There was no difference in those parameters between both groups (p>0.05). In biological parameters, SGPT, SGOT, BUN, and creatinine level, showed normal range in both groups. Conclusion: This study showed that the efficacy and safety of jamu formula was clinically comparable to piroxicam after 28 days of treatment.

Steoarthritis (OA) results from an imbalance between breakdown, repair of the tissues in the synovial joint organ and occurs as a result of multiple risk factors including trauma, overuse, and genetic predisposition. It was estimated that 9.9 million adults had symptomatic osteoarthritis of the knee in 2010. Risk factors of the condition increase with age, especially in women. Genetics, large body mass, certain occupations, repetitive knee bending or heavy lifting, and hereditary vulnerability are other factors that increase one's risk of developing the disease. 1 Some alternative therapy can be used to reduce OA. Neuromuscular electrical stimulation (NMES) is presented as a technique used by physical therapists, 2 and moderate pressure massage therapy can reduce pain and increase motion. 3 Yoga and tai chi showed VLJQL¿FDQW UHGXFWLRQV LQ SDLQ FDXVHG E\ 2$> 4 ]. Hundreds of herbal remedies are used for treating 2$ DQG WKH UHVHDUFK OLWHUDWXUH LW UHÀHFW RQO\ D VPDOO percentage of them. It seems that herbal remedies could effective to lower or stop the consumption of Nonstreroidal Antiinlammatory Drugs (NSAIDs) and to reduce the incidence of adverse effect of NSAIDs. 5 Randomized controlled trial (RCT) of traditional herbal formulation administrated by topical from chamomile oil, can decrease pain and consumption of analgesic. 6 A lot of studies about oral herbal administrated are increasing and also interesting because it is compare with NSAIDs such as Chinese herbal recipes versus diclofenac. It shows that herbal recipes are as effective than conventional drug to reduce OA. 7 Previous study of jamu formula has been done before with pre post design and it shows jamu formula can decrease the joint pain. 8 Indonesia has several herbs formulas which have been used traditionally to reduce pain of OA. The present study was FRQGXFWHG WR LQYHVWLJDWH WKH HI¿FDF\ DQG safety of traditional herbs formula that consist of &XUFXPD [DQWKRUUKL]D rhizome, &HQWHOOD DVLDWLFD herbs, &XUFXPD GRPHVWLFD rhizome, )RHQLFXOXP vulgare seeds, Orthosiphon stamineus leaves, Phyllantus niruri herbs, Equisetum debile herbs. The HI¿FDF\ RI IRUPXOD ZRXOG EH FRPSDUHG WR SLUR[LFDP The safety of formula would investigated by examined the kidney and heart function through evaluate the values of SGOT, SGPT, BUN, and creatinine.
Ten mg capsule of commercially marketed generic piroxicam were provided by PT. Indofarma (Indonesia). Subjects were selected randomly which use piroxicam, are presribed once daily 1 capsule, after meal.

Inclusion and exclusion criteria
Inclusion criteria of subject for this study were as follow: age within 50 -70 years old, Visual Analogue 6FDOH 9$6 WKDW FODVVL¿HG DV PHGLXP RU OLJKW cathegory with VAS 70 9$6 ! VFRUH QR KLVWRU\ of allergic to herbal drugs, and did not take any other medication (analgesic, NSAIDs, etc) at least 2 weeks before intervention (washed out period). Exclusion criteria of subject included having complication diseases (subject's medical record), gastritic disorder, ulcus pepticus or ulcus duodenum, allergic of bitter herbs, hypersentitive of curcumin, and taking medication during the study. Among 30 physicians and 123 patients were participated in this study. The physicians were from 20 regencies in Indonesia, who involved in 6DLQWL¿NDVL -DPX 6-SURJUDP KHOG E\ 0LQLVWU\ RI Health Republic of Indonesia (Fig. 1). Prior to receive treatment , all patient were checked on VAS score, PGAP functional status assessment (FSA), Short Form (SF-36), SGOT, SGPT, BUN, and creatinine. Every subject who had inclusion criteria, received form of compliance, and they should signed the form after they taken the jamu formula or piroxicam as well as when they forgot to take it.
Besides VAS, this study used PGAP functional status assessment (FSA) to demonstrates its reliability in the dimension of degree of dependence in performing basic activities of daily living. There are three dimensions of this measurement namely dependency, GLI¿FXOW\ DQG SDLQ IRU GLIIHUHQW DFWLYLWLHV RI GDLO\ living (Table 1) (Table 8).

DISCUSSION
A challenge osteoarthritis treatment is deciding which medications will provide the greatest symptom relief ZLWK ORZHVW VHULRXV DGYHUVH HIIHFWV> 11 ]. Meanwhile, people who use of complementary and alternative medicine (CAM) belief that using"natural" treatments are safer than conventional medical WUHDWPHQWV> 12 ]. This study indicates the excellent HI¿FDF\ DQG VDIHW\ RI WKH MDPX IRUPXOD DQG these promising OA symptoms relief result when compared with piroxicam as standart drug. Pain of WKH 2$ SDWLHQW ZDV VLJQL¿FDQWO\ UHGXFHG DIWHU RQH week of formula intervention and much better after the end of intervention (day 28). The formula was found to be safe based on SGPT, SGOT, BUN, and creatinine level, showed in normal range.   25 ] activities. Although, piroxicam group was an increased biological parameters but it still showed in normal range.
The knowledge of Jamu is part of the public health sector within the Indonesian health system. Jamu or herbal medicine in Indonesia has a important role in achieving a better equity of primary health care. Jamu  in the daily life of many Indonesians have been used mainly for self-medication. Traditional/herbal medicine has its own market, providing medication to some of the QHHG RI ,QGRQHVLDQ SHRSOH 'LYHUVLW\ ÀH[LELOLW\ HDV\ accessibility, broad continuing acceptance, relative low cost, low levels of technological input, relative low side effects and growing economic importance are some of the positive features of Jamu.
In conclusion, the study found that osteoarthritis herb formula is effective and safe alternative for pain UHOLHI RI 2$ DQG FOLQLFDOO\ FRPSDUDEOH HI¿FDF\ DQG safety to piroxicam after 28 days intervention.