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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00491595
Recruitment Status : Completed
First Posted : June 26, 2007
Last Update Posted : June 26, 2007
National Cancer Institute (NCI)
Information provided by:
University of North Carolina, Chapel Hill

Brief Summary:
The purpose of this research study is to examine the safety of specific soy components, known as isoflavones, and to find out what effects (good and bad) these components have on tissues that are sensitive to the hormone estrogen in healthy, post-menopausal women. Isoflavones are compounds that occur naturally in soybeans and can be extracted to put in to capsule form or add to foods. The capsule formulation being used in this study is considered an investigational drug. This research is being done because many scientists believe that isoflavones may play a role in the prevention of some kinds of cancer. While isoflavones have been safely consumed in foods for centuries, we need to know if these soy components are safe to take in higher doses when they are extracted from foods and provided in a supplement form. We plan to test the safety and effects of the soy isoflavones known as genistein, daidzein and glycitein.

Condition or disease Intervention/treatment Phase
Drug Toxicity Drug: High Dose Soy isoflavones Phase 1

Expanded Access : University of North Carolina has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Detailed Description:
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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Official Title: Phase I Multiple-Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women
Study Start Date : March 2004
Actual Study Completion Date : July 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Primary Outcome Measures :
  1. DNA damage, apoptosis, estrogenic effects and changes in gene expression [ Time Frame: 112 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00491595

Sponsors and Collaborators
University of North Carolina
National Cancer Institute (NCI)
Principal Investigator: Steven H Zeisel, MD, PhD UNC at Chapel Hill Identifier: NCT00491595     History of Changes
Other Study ID Numbers: NCI-N01-CN-75035
First Posted: June 26, 2007    Key Record Dates
Last Update Posted: June 26, 2007
Last Verified: June 2007

Keywords provided by University of North Carolina, Chapel Hill:
Soy isoflavones
Estrogenic effects

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders