Trial Information

A Taiwan Isoflavone Multicenter Study (TIMS)

Consumption of soy-based foods is associated with a number of health benefits, including
lower risk of cardiovascular disease, breast and prostate cancer, attenuated menopausal
symptoms and prevention of bone loss with age.

In order to investigate the effect of isoflavone on bone mineral density (BMD) and in Taiwan
women with postmenopausal osteopenia, a Taiwan Isoflavone Multicentric Enrollment Study
(TIMS) is designed. Included in the study will be Taiwanese, postmenopausal women aged >45
and < 65 years, menopaused for at least 12 months and less than 10 years. Three medical
centers will participate and enroll 140 women in every center. Inclusion will be on the
basis of a lumbar bone mineral density (BMD) lower than 1 SD compared with young age women
(T score) by DXA. Women with prevalent fractures (any kind of fragility fracture, vertebral
or nonvertebral fracture) are excluded as well as those presenting secondary osteoporosis or
having been treated with medications that could affect bone metabolism. This study is
designed as a 2-year, double-blind, placebo-controlled, two-arm, parallel group study that
randomizes the women to the oral administration of 300 mg isoflavone aglycone/day or
placebo. All patients receive a daily supplement of 600 mg calcium and 300U of Vit D3. The
primary endpoint of the study is to evaluate the effect of isoflavone aglycone on BMD. The
secondary endpoint of the study will be to evaluate the effect of Isoflavone aglycone on the
metabolic indicators of osteoporosis, blood pressure, blood sugar and insulin level, insulin
resistance (HOMA-IR), lipid profile, markers of arthrosclerosis (adiponectin and hsCRP),
myocardial infarction rate, cardiovascular mortality, cerebrovascular accident rate,
cerebrovascular mortality, all cause mortality and symptomatic relief of menopausal
syndrome, BMD reading will be done concomitantly by 3 experts, e.g. one from each
participating center. All blood test and urine examination will be done at one center for
control of quality. The blood count, biochemistry (including: GOT, GPT, BUN, creatinine),
mammography, and gynecological sonography (especially uterus) will be performed to monitor
the side effects.

Power calculations have been based on the hypothesis that isoflavone-treated patients would
get 2.5% benefit in BMD than placebo-treated patients in postmenopausal women. Statistical
tests have been designed to have a power of 80%, with a type I error equal to 5%. This study
should verify the hypothesis that isoflavone significantly increase the BMD in Asian
postmenopausal osteopenic women.