Red Clover and Lifestyle Changes to Contrast Menopausal Symptoms in Premenopausal Breast Cancer Patients Given Tamoxifen

NCT03844685 | Completed Phase 2

• 1 other identifier: INT 101/11
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective double-blind randomized trial of red clover extract (Promensil) vs placebo in surgically-treated premenopausal women with estrogen receptor-positive breast cancer taking tamoxifen

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Menopause Rating Scale (MRS)

  Full name of questionnaire is "Menopause Rating Scale" ; The total score of the MRS ranges between 0 (asymptomatic) and 44 (highest degree of complaints). the ranges are: 0-4 no/little symptoms, 5-8 mild, 9-15 moderate and 16/16+ severe. The sub-scale are: Psychological score, (Question N° 4-7), Somatic score (Question N° 1-3; 11), Urogenital score (Question N° 8-10). The subscales are combined in a total MRS score.

  24 months

• weight gain (kg)

  24 months

• insulin resistance

  fasting blood glucose x fasting blood insulin (HOMA-IR)

  24 months

Secondary Outcomes (4)

• endometrial thickness

  24 months

• breast density

  24 months

• growth of breast cancer cell lines highly expressing estrogen receptors

  24 months

• transcript expression of estrogen-regulated genes in breast cancer cell lines highly expressing estrogen receptors

  24 months

Study Arms (2)

Treatment group

EXPERIMENTAL

1 tablet /day of MCE-11 (Promensil) taken orally for 24 months

Drug: Promensil

Placebo group

PLACEBO COMPARATOR

Placebo tablet (without active principle) given once a day for 24 months

Drug: Placebo Oral Tablet

Interventions

Promensil DRUG

1 tablet (80 mg) /day of MCE-11 (Promensil) taken orally for 24 months

Treatment group

Placebo Oral Tablet DRUG

Placebo tablet (80 mg) (without active principle) given once a day for 24 months

Placebo group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Histologically confirmed operable ER-positive breast cancer
• Can be ductal carcinoma in situ (DCIS)
• Absence of locoregional relapse or distant metastasis
• Normal ovarian function
• Menopause Rating Score \> or equal to 8
• Signed informed consent to participate

You may not qualify if:

• Menopause Rating Score \<8
• Menopausal at diagnosis or at surgery
• Previous malignancies other than in situ cervical carcinoma or non-melanoma skin cancer
• Breast cancer recurrence
• Metastatic breast cancer
• Non-epithelial breast cancer at histological examination
• In situ lobular breast cancer
• Participation in other randomized clinical trials that could interfere with current study
• Living distant from center and unable to attend for check-ups and meetings.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Cristina Ferraris

Milan, 20133, Italy

Location

Related Publications (19)

• Dornstauder E, Jisa E, Unterrieder I, Krenn L, Kubelka W, Jungbauer A. Estrogenic activity of two standardized red clover extracts (Menoflavon) intended for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol. 2001 Jul;78(1):67-75. doi: 10.1016/s0960-0760(01)00075-9.

  PMID: 11530286 RESULT

• Piersen CE, Booth NL, Sun Y, Liang W, Burdette JE, van Breemen RB, Geller SE, Gu C, Banuvar S, Shulman LP, Bolton JL, Farnsworth NR. Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model. Curr Med Chem. 2004 Jun;11(11):1361-74. doi: 10.2174/0929867043365134.

  PMID: 15180571 RESULT

• Imhof M, Molzer S, Imhof M. Effects of soy isoflavones on 17beta-estradiol-induced proliferation of MCF-7 breast cancer cells. Toxicol In Vitro. 2008 Sep;22(6):1452-60. doi: 10.1016/j.tiv.2008.04.018. Epub 2008 May 4.

  PMID: 18554862 RESULT

• Howes J, Waring M, Huang L, Howes LG. Long-term pharmacokinetics of an extract of isoflavones from red clover (Trifolium pratense). J Altern Complement Med. 2002 Apr;8(2):135-42. doi: 10.1089/107555302317371424.

  PMID: 12006121 RESULT

• Kawakita S, Marotta F, Naito Y, Gumaste U, Jain S, Tsuchiya J, Minelli E. Effect of an isoflavones-containing red clover preparation and alkaline supplementation on bone metabolism in ovariectomized rats. Clin Interv Aging. 2009;4:91-100. doi: 10.2147/cia.s4164. Epub 2009 May 14.

  PMID: 19503771 RESULT

• Atkinson C, Compston JE, Day NE, Dowsett M, Bingham SA. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2004 Feb;79(2):326-33. doi: 10.1093/ajcn/79.2.326.

  PMID: 14749241 RESULT

• Lipovac M, Chedraui P, Gruenhut C, Gocan A, Stammler M, Imhof M. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas. 2010 Mar;65(3):258-61. doi: 10.1016/j.maturitas.2009.10.014. Epub 2009 Nov 30.

  PMID: 19948385 RESULT

• Imhof M, Gocan A, Reithmayr F, Lipovac M, Schimitzek C, Chedraui P, Huber J. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Maturitas. 2006 Aug 20;55(1):76-81. doi: 10.1016/j.maturitas.2006.01.006. Epub 2006 Mar 2.

  PMID: 16513301 RESULT

• Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol. 2005 Nov;21(5):257-64. doi: 10.1080/09513590500361192.

  PMID: 16373244 RESULT

• Terzic MM, Dotlic J, Maricic S, Mihailovic T, Tosic-Race B. Influence of red clover-derived isoflavones on serum lipid profile in postmenopausal women. J Obstet Gynaecol Res. 2009 Dec;35(6):1091-5. doi: 10.1111/j.1447-0756.2009.001059.x.

  PMID: 20144173 RESULT

• Chedraui P, San Miguel G, Hidalgo L, Morocho N, Ross S. Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index. Gynecol Endocrinol. 2008 Nov;24(11):620-4. doi: 10.1080/09513590802288283.

  PMID: 19031218 RESULT

• Mueller M, Jungbauer A. Red clover extract: a putative source for simultaneous treatment of menopausal disorders and the metabolic syndrome. Menopause. 2008 Nov-Dec;15(6):1120-31. doi: 10.1097/gme.0b013e31817062ce.

  PMID: 18724264 RESULT

• Simoncini T, Fornari L, Mannella P, Caruso A, Garibaldi S, Baldacci C, Genazzani AR. Activation of nitric oxide synthesis in human endothelial cells by red clover extracts. Menopause. 2005 Jan-Feb;12(1):69-77. doi: 10.1097/00042192-200512010-00013.

  PMID: 15668603 RESULT

• Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ. Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1066-71. doi: 10.1161/01.ATV.0000072967.97296.4A. Epub 2003 Apr 24.

  PMID: 12714433 RESULT

• Guha N, Kwan ML, Quesenberry CP Jr, Weltzien EK, Castillo AL, Caan BJ. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2009 Nov;118(2):395-405. doi: 10.1007/s10549-009-0321-5. Epub 2009 Feb 17.

  PMID: 19221874 RESULT

• Chlebowski RT, Schwartz AG, Wakelee H, Anderson GL, Stefanick ML, Manson JE, Rodabough RJ, Chien JW, Wactawski-Wende J, Gass M, Kotchen JM, Johnson KC, O'Sullivan MJ, Ockene JK, Chen C, Hubbell FA; Women's Health Initiative Investigators. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009 Oct 10;374(9697):1243-51. doi: 10.1016/S0140-6736(09)61526-9. Epub 2009 Sep 18.

  PMID: 19767090 RESULT

• Cross HS, Kallay E, Lechner D, Gerdenitsch W, Adlercreutz H, Armbrecht HJ. Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas. J Nutr. 2004 May;134(5):1207S-1212S. doi: 10.1093/jn/134.5.1207S.

  PMID: 15113973 RESULT

• Horn-Ross PL, John EM, Canchola AJ, Stewart SL, Lee MM. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst. 2003 Aug 6;95(15):1158-64. doi: 10.1093/jnci/djg015.

  PMID: 12902445 RESULT

• Horn-Ross PL, Hoggatt KJ, Lee MM. Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomarkers Prev. 2002 Jan;11(1):43-9.

  PMID: 11815400 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Promensil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patient and personnel involved in trial masked to treatment vs. placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, double-blind clinical trial

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: February 18, 2019
• Study Start: July 5, 2012
• Primary Completion: March 25, 2014
• Study Completion: February 23, 2016
• Last Updated: February 20, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)