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Hot flashes in menopausal women are an increasingly significant public health problem in the U.S. Current standard therapy includes estrogen and/or other hormones, the risks of which are more evident from recent clinical trials. TU-061 is a botanical medicinal product composed of aqueous extracts of cinnamon, rhubarb, licorice, and peach kernel, with Na2SO4. TU-061 is a “Kampo” (traditional medicine) therapeutic product, and was approved as a prescription drug in Japan in 1986, primarily for treatment of constipation and menopausal hot flashes.
Animal studies and clinical trials with TU-061 have provided limited information regarding its mechanisms of action, suggesting that TU-061 modulates calcitonin gene-related peptide (CGRP)-stimulated elevation of skin temperature, and can stimulate proliferation of estrogen-dependent human breast cancer (MCF-7) cells. Post-marketing surveillance data indicate that TU-061 is safe, with the incidence of adverse reactions since 1994 estimated to be less than 0.00475 %. An IND application for TU-061 will be submitted to the FDA in October, 2005.
In the study proposed herein, we hypothesize that TU-061 treatment will exert biological activities related to hot flashes that are detectable in blood and/or cervical tissue. The goal of this research is to investigate, in a pilot, exploratory protocol, the short-term (hours) and long-term (several weeks) effects of oral administration of TU-061 on circulating and tissue biomarkers in healthy, newly postmenopausal women. In this placebo-controlled study, the primary endpoints are changes in circulating levels of CGRP (and other biomarkers) and in the products of various genes important to reproductive function in cervical tissue. A single-dose intervention will be utilized, with a dose of TU-061 that has been found by Tsumura and Co. to be safe and effective. Data related to hot flashes, menopausal symptoms, QOL, and safety will be considered secondary outcome measures. This research will extend knowledge by identifying potentially useful circulating and tissue biomarkers of exposure to TU-061 that will be essential for consideration of a follow-up, more detailed dose-finding study.
