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Breast CancerPhase 2NCT03844685

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

A Phase 2 study testing Promensil in people with Breast Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 60 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Promensil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
88 participants
Where
1 siteItaly
Study dates
5 Jul 2012to 23 Feb 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Cristina Ferraris

    Milan, 20133

Other trials in Italy

About this study

Official title: RED CLOVER EXTRACT (PROMENSIL) AND LIFESTYLE CHANGES TO CONTRAST MENOPAUSAL SYMPTOMS IN PREMENOPAUSAL WOMEN WITH HORMONE-SENSITIVE BREAST CANCER RECEIVING ADJUVANT ANTI-ESTROGEN THERAPY

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

Read the detailed description

Premenopausal women with ER-positive breast cancer treated by surgery and receiving postoperative tamoxifen with or without LHRH analogues, who may have received pre or postoperative chemotherapy, or immunotherapy (for HER2-positive disease), are recruited to a double-blind randomized clinical trial, to receive either a dry extract of red clover (Promensil) as one tablet/day orally containing 80 mg isoflavones (treatment group), or one oral tablet/day without active principle (placebo group) for 24 months. All patients receive a diet-lifestyle intervention involving meetings with a dietician (physician) scheduled once a month for the first 6 months, and every 3 months thereafter. The dietician encourages patients to adhere to a macronutrient-balanced, low glycaemic load Mediterranean-type diet with personalized recommendations to increase intakes of unrefined cereals, pulses, vegetables, unrefined vegetable fats (e.g. olive oil, nuts, oil-containing seeds), and fish, and reduce intake of high-glycaemic-index foods and saturated animal fats. Patients are also encouraged to undertake regular physical activity. Outcomes are Menopausal Rating Score (MRS), body mass index (BMI), waist and hip girth, insulin resistance, and levels of cholesterol, triglycerides, and sex hormones.

The safety of the red clover preparation is assessed by pelvic ultrasound and mammograms for endometrial thickness and breast density, and by evaluation of the effects of the serum from treated and placebo patients on ER-positive BC cell lines.

Conditions
Breast Cancer
Being tested
Promensil, Placebo Oral Tablet
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PromensilDrug

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

  • Placebo Oral TabletDrug

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

Study groups in NCT03844685
Study groupRoleWhat they receive
Treatment groupExperimental1 tablet /day of MCE-11 (Promensil) taken orally for 24 months
Receives: Drug: Promensil
Placebo groupPlacebo comparatorPlacebo tablet (without active principle) given once a day for 24 months
Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 months

  2. weight gain (kg)

    Measured: 24 months

  3. insulin resistance

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

    Measured: 24 months

Secondary outcomes (4)

  1. endometrial thickness

    assessed by annual pelvic ultrasound (mm)

    Measured: 24 months

  2. breast density

    assessed by annual mammography (BI-RADS)

    Measured: 24 months

  3. growth of breast cancer cell lines highly expressing estrogen receptors

    OD Units

    Measured: 24 months

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

    transcript levels

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2019
  2. Study start5 Jul 2012
  3. Primary completion25 Mar 2014
  4. Study completion23 Feb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomized, double-blind clinical trial
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03844685
Sponsor's protocol ID
INT 101/11
Status last verified
Feb 2019
First submitted
20 Dec 2018
Last updated
20 Feb 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 11530286

  • 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.

    PubMed 15180571

  • 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.

    PubMed 18554862

  • 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.

    PubMed 12006121

  • 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.

    PubMed 19503771

  • 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.

    PubMed 14749241

  • 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.

    PubMed 19948385

  • 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.

    PubMed 16513301

  • 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.

    PubMed 16373244

  • 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.

    PubMed 20144173

  • 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.

    PubMed 19031218

  • 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.

    PubMed 18724264

  • 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.

    PubMed 15668603

  • 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.

    PubMed 12714433

  • 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.

    PubMed 19221874

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Promensil in people with Breast Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Menopause Rating Scale (MRS) (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03844685, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2019.

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