Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention

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.
ClinicalTrials.gov Identifier: NCT00723398
Recruitment Status : Completed
First Posted : July 28, 2008
Results First Posted : November 1, 2018
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Andrea Manni, Milton S. Hershey Medical Center

Brief Summary:
The overall hypothesis is that the combination of a low dose of the antiestrogen Raloxifene with omega-3 fatty acids will exert a synergistic breast cancer chemopreventive effect due to the crosstalk of their downstream cellular effects leading to decreased proliferation and increased apoptosis of premalignant mammary cells. Based on the investigators hypothesis that upregulation of functional estrogen receptors in the premalignant lesions is also responsible for the development of hormone independent tumors, the investigators postulate that the combination of antiestrogens and omega-3 fatty acids will reduce the development of both hormone-dependent and -independent tumors. At present, there are no known interventions able to decrease the development of hormone-independent tumors, which are more prevalent, more aggressive, leading to the patient's demise. In addition, the investigators postulate that this approach will be safe since it will combine a lower and hence a less toxic dose of Raloxifene with the administration of omega-3 fatty acids which are known to have health benefits, i.e., reduction in cardiovascular risk, beyond their possible chemo preventive effect in breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Dietary Supplement: Lovaza 4gm oral Drug: Raloxifene 60 Mg Oral Tablet Drug: Raloxifene 30 Mg Oral Tablet Drug: Lovaza 4gm & Raloxifene 30mg Not Applicable

Detailed Description:

The main objectives of this study are to determine the individual and combined effects of Raloxifene and omega-3 fatty acids on surrogate markers of breast cancer development in healthy, postmenopausal women. The primary endpoint will be mammographic density for which the study has been powered. Breast density is a major risk factor for breast cancer and hence it is chosen to evaluate the potential chemopreventive efficacy of our interventions. Secondary endpoints would include markers of oxidative stress, parameters of estrogen metabolism, markers of inflammation, and markers of IGF-I signaling, all of which have been shown in the literature to have an influence on mammary carcinogenesis.

Study Population: Healthy, postmenopausal women between the ages of 35-70 years, undergoing yearly mammograms as part of routine screening practice.

Method of Identification of Subjects/Samples/Medical Records: Women reporting for yearly mammograms will be considered for this protocol. They will be given first a screening questionnaire to rule out any co-existing medical condition that would predispose them to thromboembolic events.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Combination of Low Dose Antiestrogens With Omega-3 Fatty Acids for Prevention of Hormone-independent Breast Cancer
Study Start Date : March 2009
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Raloxifene

Arm Intervention/treatment
No Intervention: Group 1: Control
Control, no intervention
Experimental: Group 2: Raloxifene 60 Mg Oral Tablet
Raloxifene 60 mg Orally Daily
Drug: Raloxifene 60 Mg Oral Tablet
60 mg orally every day for two years
Other Name: Evista 60 Mg Oral Tablet

Experimental: Group 3: Raloxifene 30 Mg Oral Tablet
Raloxifene 30 mg Orally Daily
Drug: Raloxifene 30 Mg Oral Tablet
30 mg orally daily for two years
Other Name: Evista 30 Mg Oral Tablet

Experimental: Group 4: Lovaza 4 gm oral
Lovaza 4 gm/day Orally with Meals
Dietary Supplement: Lovaza 4gm oral
Dietary supplement; Take 4 mg oral capsules daily
Other Name: Omega-3 Fatty Acid Capsules; Fish Oil capsules; Triklo

Experimental: Group 5: Lovaza 4gm & Raloxifene 30mg
Lovaza 4 gm/day oral capsule with meals plus Raloxifene 30 mg oral tablet daily
Drug: Lovaza 4gm & Raloxifene 30mg
Lovaza 4gm and Raloxifene 30 Mg orally once per day for 2 years
Other Name: Pitavastatin 4 gm and Evista 30 mg oral tablet




Primary Outcome Measures :
  1. Change in Absolute Breast Density [ Time Frame: 2 years ]
    Change of absolute breast density as indicated by mammography from baseline to Year +1 and completion of study (Year +2). No other mammograms will be obtained or used for the purpose of this study. Absolute breast density volume is based on breast thickness and the x-ray attenuation at each pixel of the image.


Secondary Outcome Measures :
  1. Changes in Biomarkers for Oxidative Stress:Urinary 8-(Isoprostane) F-2α [ Time Frame: 1 year ]
    Changes in biomarkers for oxidative stress. Specific time points for evaluation are baseline and Year +1 (only). Urinary 8-(isoprostane) F-2α as measured through urine analysis.

  2. Changes in Biomarkers for Oxidative Stress: Urinary 8-hydroxy-deoxyguansine [ Time Frame: 1 year ]
    Changes in biomarkers for oxidative stress. Specific time points for evaluation are baseline and Year +1 (only). Urinary 8-hydroxy-deoxyguansine as measured through urinary analysis.

  3. Changes in Biomarkers for Estrogen Metabolism: 2-hydroxy Estrone (Urinary 2-OHE1) and 16-α-hydroxy Estrone (16α-OHE1) [ Time Frame: 1 year ]
    Changes in biomarkers for estrogen metabolism: 2-hydroxy estrone (Urinary 2-OHE1) and 16-α-hydroxy estrone (16α-OHE1) as measured by urinary analysis. Specific time points for evaluation are baseline and Year +1 (only).

  4. Changes in Serum Biomarkers for Inflammation From Levels of High Sensitivity C-reactive Protein (hsCRP) and Interleukin 6 (IL-6) [ Time Frame: 1 Year ]
    Changes in serum biomarkers for inflammation including highly sensitive C-reactive protein and IL-6 obtained through a blood draw. Specific time points for evaluation are baseline and Year +1 (only).

  5. Changes in Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor-1 Binding Protein-3 (IGFBP-3) [ Time Frame: 1 year ]
    Changes in insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 binding protein-3 (IGFBP-3) obtained through blood sample. Specific time points for evaluation are baseline and Year +1 (only).

  6. Changes in Serum Lipid Levels [ Time Frame: 2 years ]
    Changes in serum lipid levels as measured through total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Specific time points for evaluation are baseline, Year +1, and Year 2.

  7. Changes in Complete Blood Count: Red Blood Cells [ Time Frame: 2 years ]
    Changes in complete blood count levels as measured through red blood cells (RBC). Specific time points for evaluation are baseline, Year +1, and Year 2.

  8. Changes in Complete Blood Count: Hemoglobin [ Time Frame: 2 years ]
    Changes in complete blood count levels as measured through hemoglobin. Specific time points for evaluation are baseline, Year +1, and Year 2.

  9. Changes in Complete Blood Count: Hematocrit [ Time Frame: 2 years ]
    Changes in complete blood count levels as measured through hematocrit percentage. Specific time points for evaluation are baseline, Year +1, and Year 2.

  10. Changes in Complete Blood Count: White Blood Cells and Platelets [ Time Frame: 2 years ]
    Changes in complete blood count levels as measured through white blood cells (WBC) and platelets. Specific time points for evaluation are baseline, Year +1, and Year 2.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal status defined as history of at least 12 months without spontaneous menstrual bleeding or a documented hysterectomy and bilateral salpingo oophorectomy
  • Breast density greater than 25%
  • No hormone replacement therapy for at least six months prior to entry into this study
  • Non-smokers.

Exclusion Criteria:

  • History of stroke, pulmonary embolism or deep vein thrombosis
  • History of atherosclerotic heart disease
  • Presence of any known hypercoagulable state either congenital (e.g., protein S deficiency) or acquired (e.g., corticosteroid treatment)
  • Diabetes mellitus
  • Uncontrolled hypertension (BP ≥140/90)
  • Presence of a psychiatric condition that would interfere with adherence to the protocol.

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 ClinicalTrials.gov identifier (NCT number): NCT00723398


Locations
Layout table for location information
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Andrea Manni, MD Penn State University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Andrea Manni, Professor and Chief Division of Endocrinology, Diabetes, and Metabolism, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00723398     History of Changes
Other Study ID Numbers: 26970
First Posted: July 28, 2008    Key Record Dates
Results First Posted: November 1, 2018
Last Update Posted: November 1, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Andrea Manni, Milton S. Hershey Medical Center:
omega-3 fatty acids
antiestrogens
breast cancer prevention
breast density
biomarkers of mammary carcinogenesis

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pitavastatin
Raloxifene Hydrochloride
Estrogen Receptor Modulators
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents