Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue

NCT ID: NCT00908791

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2013-03-31

Brief Summary

Conjugated Linoleic Acid (CLA) is obtained in the human diet by consumption of foods containing ruminant fat. Milk and dairy products have shown the highest amounts of CLA. Clarinol (CLA), is considered a natural supplement and is not regulated by the Food and Drug Administration (FDA). CLA is known to inhibit proliferation of human breast cancer cells and tumors in rodent breast cancer models and reduced Spot 14 (THRSP, S14) and Fatty Acid Synthase (FASN) gene expression in breast cancer cells and tht the two major CLA isomers used in nutritional supplements (C9, t11 and t10, c12) were equipotent in reducing breast cancer cell growth. This study looks at the hypothesis that S14 expression is decreased by CLA and will characterize the major pharmacodynamic (PD) effects of CLA in newly diagnosed Breast cancer patients on Tumor tissue lipogenic pathway. FASN, S14 and Lipoprotein Lipase (LPL), Ki67 and apoptotic index expression will be assessed by quantitative immunohistochemistry (IHC) in initial breast cancer biopsies and compared to that in resected breast tumor tissue after the study subject has been taking CLA for ten to twenty-eight days. Tissue from adjacent breast adipocytes will also be analyzed to determine whether adipose tissue effects can serve as a surrogate marker for those in tumor tissue. A sample of the original biopsy will be compared to the tumor resection sample to determine the levels of CLA in the breast cancer cells.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CLA

open-label, single-institution proof of principle study of oral CLA in patients with newly diagnosed adenocarcinoma of the breast.

Group Type: EXPERIMENTAL

Conjugated Linoleic Acid (CLA)

Intervention Type: DRUG

Conjugated linoleic acid (CLA, Clarinol™) oral soft gel capsules will be administered in an open-labeled, manner to all subjects enrolled in the study. Subjects will be treated with 7.5 grams of oral CLA daily, taken in divided dose, twice daily between 8 am and 12 noon and between 8 pm and 12 midnight. CLA will be taken for a minimum of ten days prior to surgical resection of their breast malignancy. In the event that the subject's surgical resection date is delayed, subjects may take CLA for up to 28 days. The last dose of CLA prior to the surgical resection will be taken at 12 midnight or as close as possible to that time and the patient will record the time of the last dosing.

Interventions

Conjugated Linoleic Acid (CLA)

Conjugated linoleic acid (CLA, Clarinol™) oral soft gel capsules will be administered in an open-labeled, manner to all subjects enrolled in the study. Subjects will be treated with 7.5 grams of oral CLA daily, taken in divided dose, twice daily between 8 am and 12 noon and between 8 pm and 12 midnight. CLA will be taken for a minimum of ten days prior to surgical resection of their breast malignancy. In the event that the subject's surgical resection date is delayed, subjects may take CLA for up to 28 days. The last dose of CLA prior to the surgical resection will be taken at 12 midnight or as close as possible to that time and the patient will record the time of the last dosing.

Intervention Type: DRUG

Other Intervention Names

Clarinol

Eligibility Criteria

Inclusion Criteria

• All study patients must have histologically confirmed invasive adenocarcinoma of the breast. Their breast cancer must be resectable clinical stage I or II breast cancer as defined by the current AJCC TNM Staging System (Greene FL, Page DL, Fleming ID, et al.: editors. AJCC cancer staging manual, 6th edition. New York: Springer; 2002).
• All patients must be able to and give informed consent indicating they are aware of the investigational nature of this treatment, prior to entry into the study.
• All subjects must be Age >18 years.
• All subject must have adequate hepatic and renal function documented prior to study entry to include: hepatic transaminases (AST or ALT) ≤ 1.5 times the upper limits of normal, total bilirubin ≤ 1.5 times the upper limits of normal, serum creatinine ≤ 1.5 times the upper limit of normal or eCRCl ≥ 60 mL/min.

Exclusion Criteria

• Patients who have received prior or be receiving radiation therapy for their breast cancer will be excluded.
• Patients who have received prior chemotherapy or receiving chemotherapy or hormonal therapy for their breast cancer will not be included.
• Women must be surgically sterilized or post-menopausal or women of childbearing potential must be using an adequate method of contraception. Women of childbearing potential must be using at least one of the following: oral, implanted, injectable contraceptive hormones, or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or have a partner that is sterile (e.g., vasectomy). Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study therapy. Women who are pregnant or breast-feeding and women of childbearing potential not using an adequate method of birth control will be excluded.
• Patients with gastrointestinal abnormalities including: inability to take oral medication, requirement for intravenous alimentation, or prior surgical procedures affecting nutrient /drug absorption will be excluded.
• A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded. Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, and congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrhythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth College

OTHER

Sponsor Role: collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Lionel.D.Lewis, MD

•Professor of Pharmacology and Toxicology, Geisel School of Medicine, Dartmouth

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Burton L Eisenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Norris Cotton Cancer Center

Locations

Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

D0906

Identifier Type: -

Identifier Source: org_study_id