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An herbal combination used in traditional Chinese medicine failed to improve pain and function in knee osteoarthritis (OA) in a phase II clinical trial, researchers reported.
After 8 weeks of treatment with Huo-Luo-Xiao-Ling (HLXL)-Dan, the mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale was -1.2 for HLXL and -1.4 for placebo, a between-group difference that was not statistically significant (P=0.47), according to Lixing Lao, PhD, of the University of Hong Kong, and colleagues.
In addition, the change in WOMAC function score was -1.1 for HLXL and -1.3 for placebo (P=0.51), the researchers reported online in Osteoarthritis and Cartilage.
Various formulations of HLXL have long been used in the treatment of arthritis in China. While the original formulation included only four plant extracts, the HLXL used in this study contained 11 herbs such as Angelica sinensis, Paeonia lactiflora, and Gentiana macrophylla.
Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by patients with knee OA, but long-term use has been associated with potentially troublesome adverse effects.
One report found that almost one-third of older U.S. adults turned to some type of complementary or alternative medicine for symptom relief of this common problem, but evidence for these therapies has been inconclusive.
Some studies have suggested that this herbal product was effective for arthritic conditions, and animal studies had demonstrated reductions in inflammation through effects on pro-inflammatory cytokines such as tumor necrosis factor-alpha.
However, no randomized, placebo-controlled trials have thus far been done.
Therefore, the researchers enrolled 92 patients from the University of Maryland and the Chinese University of Hong Kong who had knee OA of at least 6 months’ duration and who were taking NSAIDs or analgesics.
Before embarking on the phase II trial, however, they performed a smaller study that included 28 patients randomized to placebo or low-dose (six capsules per day), medium-dose (10 capsules per day), or high-dose (14 capsules per day) for 6 weeks.
However, because no effect was seen with the low dose and no adverse events were reported, the data and safety monitoring board recommended that the medium and high-dose groups be combined and the study extended to 8 weeks.
Participants’ mean age was 60, and the majority were Asian women. Mean baseline WOMAC pain score was 4.4 and function score was 4.5. Patients on other arthritis medications were required to have been taking stable doses for the previous month.
Other efficacy endpoints also showed no significant between-group differences. For instance, on the overall normalized WOMAC score, changes from baseline were -3.6 for the HLXL group and -4.3 for the placebo group (P=0.45), and on the patient global assessment the change was 0.4 for the HLXL group and 0.5 for the placebo group (P=0.82).
On an earlier phase I pilot study, adverse reactions associated with the high dose had included gastrointestinal events, rash, and slight increases in liver enzymes. No new safety concerns emerged in this trial, with no liver enzyme elevations above the upper limit of normal. A few cases of nausea and bloating were reported, two patients had rashes, and one patient dropped out after having an allergic reaction.
While the study showed that the herbal formulation was safe, it was no more effective for pain and function than placebo. And despite its wide acceptance in Chinese medicine, “based on the results of this study, we cannot recommend HLXL as an adjunctive therapy for treating knee OA,” Lao and colleagues wrote.
Unlike previous studies of traditional Chinese medicine, which have often been criticized as being poorly designed, this trial used a rigorous design with standard WOMAC outcomes, adequate blinding, and sufficient duration. The dosage had been determined based on earlier animal studies.
The authors noted that there were several possible explanations for the lack of efficacy seen in the trial. “The formula might not be potent enough to provide additional symptom relief for patients already on background analgesics and/or NSAIDs. The classic formula was used in ancient times when no other analgesics were available,” they observed.
Another possible reason could be that in traditional Chinese medicine, treatment is individualized according to the patient’s symptoms, so a conventional randomized trial design might not be the optimal way of evaluating efficacy.
Furthermore, the herbal formulation used was based on acetone extraction, rather than the water extraction used traditionally.
“Future studies employing individualized treatment and medications might be more appropriate to assess the efficacy of Chinese medicine treatment,” they concluded.
The study was supported by the NIH’s National Center for Complementary and Alternative Medicine.
The authors reported no financial conflicts.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 06.30.2015
Source: Med Page Today
