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Phase I Multiple-Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women

Phase 1
Not Enrolling
Drug Toxicity

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Trial Information

Phase I Multiple-Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women

This will be a double blind, Phase I, multiple dose clinical trial of orally administered
soy isoflavones (PTI G-2535, 70% unconjugated isoflavones containing genistein, daidzein,
and glycitein). This preparation will be referred to as soy isoflavones in this and all
study related documents to more accurately reflect the study drug’s content. The multiple
dose trial will last four months (112 days) and will include healthy, post-menopausal women
as determined by FSH levels and lack of spontaneous bleeding for at least one year. After
eligibility is determined, all potential subjects will ingest a soy shake to determine if
they are producers of the daidzein metabolite, equol. We expect to find approximately 30% of
our eligible subjects to be equol-producers as published in the literature. Equol producers
will be defined as individuals with plasma levels >20ug/L; non-equol producers as those with
<10ug/L 37. Individuals with intermediate equol values (> 10 ug/L to < 20 ug/L) will be
excluded from the study. Stratified randomization will assign the subjects to one of the two
groups, aiming for 30-40% equol producers in each group. Group 1 (20 subjects) will receive
a dietary supplement containing 600 mg of genistein in two doses of 300 mg (as part of a
soy isoflavones mixture) per day orally administered over an 84-day period. Group 2 (10
subjects) will receive a placebo supplement (excipients from the active formulation), orally
administered over an 84-day period. These women will be recruited from the local population
within the Research Triangle area. The study will be conducted at the UNC Hospital General
Clinical Research Center (GCRC).

Inclusion Criteria:

- Performance status 0, 1, or 2 on ECOG scale

- Acceptable hematopoietic, hepatic, and renal function (WBC≥3500 µL, platelet count ≥
100,000/ml, serum creatinine < 2.0 mg/dl, serum bilirubin ≤ 2.0 mg/dl,
transaminases < two times normal limits)

- Post-menopausal status - FSH level > 27 mIU/ml, no spontaneous bleeding > 1 year

- Normal mammogram within the last 13 months

- Normal Papanicolaou Test within the last 13 months

Exclusion Criteria:

- Serious intercurrent medical illnesses or history of seizure

- Significant cardiac disease (New York Heart Association Class III or IV)

- Abnormalities on the physical examination screen including significant abnormality of
the heart, lungs, liver, spleen, or other abdominal organs, or neurologic abnormality
Abnormalities on the biochemical screen that could be metabolically significant

- Individuals with intermediate equol values (> 10 ug/L to < 20 ug/L) on soy challenge

- Use of antibiotics within the last 3 months

- Use of hormone/estrogen therapy or SERMs within the last 3 months

- Abnormal thyroid or endocrine function tests; or current use of thyroid medication

- BMI at or above 35

- History of complete hysterectomy or oophorectomy

- High risk of breast cancer (5-year risk of >1.9%) based on NCI’s Breast Cancer Risk
Assessment Tool

- A history of a malignancy active or initially diagnosed within 2 years other than
curatively treated non-melanoma carcinoma of the skin

- History of substance abuse or addiction

- Alcohol intake of greater than 2 drinks/day or 14 drinks/week

- Tobacco use

- Diets containing more than estimated intake of 20 mg genistein/day or 40mg
isoflavone/day AND unwilling/unable to reduce soy intake to below this level during
the study period

- Use of supplements containing phytoestrogens or that have estrogenic side effects
within 1 month of study

- Pre-menopausal or pregnant

- Inability to read and comprehend the Informed Consent

- Life expectancy < 6 months

- History of breast cancer

- Known soy intolerance

- On chemotherapy within the last 2 years

- Inability to obtain an endometrial biopsy

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind

Outcome Measure:

DNA damage, apoptosis, estrogenic effects and changes in gene expression

Outcome Time Frame:

112 days

Principal Investigator

Steven H Zeisel, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC at Chapel Hill


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

July 2005

Related Keywords:

  • Drug Toxicity
  • Soy isoflavones
  • Genotoxicity
  • Apoptosis
  • Estrogenic effects
  • Drug Toxicity