A clinical surrogate model for proof of efficacy of external phytomedicines for muscle pain. Results of a randomized, placebo-controlled clinical study in volunteers with muscle pain due to physical training

Abstract

PURPOSE: Surrogate models have been postulated for (re-)registration of external remedies for pain, whose active substances are in accordance to monographs. In a new human model, we investigated an ointment consisting of high dosed herbal ingredients. METHODS: We conducted a clinical study in 32 healthy volunteers. Four muscle regions were treated with the ointments (verum on the one side and placebo on the other) in a randomized and doubleblinded manner immediately after a standardized physical exercise with individual intensity, as well as after 1, 2 and 24 h. Acute muscle pain and muscle tension for each region was documented repeatedly during the following two days by visual analogue scale (VAS). Primary outcome parameter was the difference of pain during the follow up given as area under the curve (AUC) of VAS for corresponding right and left regions, treated with verum or placebo. Also the difference of muscle tension was documented and evaluated in an analogous way. RESULTS: 30 out of 32 included patients finished the study, but developed only moderate muscle pain, with highest pain scores for extension muscles of the arm. There was less pain in the course for the verum in 3 of the 4 regions, the mean difference of individual AUCs was at highest for the extension (triceps) muscles of the arm, but between-group differences failed significance. Feeling of muscle tension was higher than that of pain, with smaller mean AUCs of verum in all 4 regions; the differences were significant in total (p<0.02) and in 2 of 4 single regions. CONCLUSIONS: Physical exercise was not intensive enough to exert clear symptoms. Our volunteers with sportive background seem not to show severe symptoms of muscle pain and muscle tension even after an intensive training. Despite low levels of symptoms, verum showed better courses of muscle tension and muscle pain. For future studies it seems better not to use volunteers with sportive background but totally untrained persons in order to achieve pronounced symptoms. The model is feasible, sensitive, inexpensive and is much more clinically relevant than those, focusing on perfusion parameters of skin.