- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00908791
Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
January 7, 2019 updated by: Lionel.D.Lewis, MD, Dartmouth-Hitchcock Medical Center
An in Vivo Proof of Principle Trial to Determine Whether the Nutritional Supplement Conjugated Linoleic Acid (CLA, Clarinol™) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: CLA
open-label, single-institution proof of principle study of oral CLA in patients with newly diagnosed adenocarcinoma of the breast.
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Spot 14 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
Time Frame: Up to 28 days
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To determine whether ≥ 10 days of CLA consumption suppresses Spot 14 expression in breast cancer tissue in vivo.
The staining intensities scoring system used is: no immuostaining (0), weak staining (1), and strong staining (2).
The scoring system used objectively and quantitatively assesses the expression of Spot 14, fatty acid synthase, and lipoprotein lipase using the image processing and analysis software Image-Pro Plus™ (MediaCybernetics).
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Up to 28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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To determine whether ≥ 10 days of CLA consumption suppresses FASN expression in breast cancer tissue in vivo.
The staining intensities scoring system used is: no immuostaining (0), weak staining (1), and strong staining (2).
The scoring system used objectively and quantitatively assesses the expression of Spot 14, fatty acid synthase, and lipoprotein lipase using the image processing and analysis software Image-Pro Plus™ (MediaCybernetics).
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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To determine whether ≥ 10 days of CLA consumption suppresses LPL expression in brest cancer tissue in vivo.
The staining intensities scoring system used is: no immuostaining (0), weak staining (1), and strong staining (2).
The scoring system used objectively and quantitatively assesses the expression of Spot 14, fatty acid synthase, and lipoprotein lipase using the image processing and analysis software Image-Pro Plus™ (MediaCybernetics).
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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To determine whether ≥ 10 days of CLA consumption impacts the status of tumor proliferation by calculating the percentage of cells expressing Ki67.
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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To determine whether ≥ 10 days of CLA consumption impacts the status of tumor cell apoptosis by measuring the presence of immunostaining for cleaved caspase 3.
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
Time Frame: Pre-CLA treatment and up to 2 years Post-CLA treatment
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Pre-CLA treatment and up to 2 years Post-CLA treatment
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Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Time Frame: 2 months
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2 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Burton L Eisenberg, MD, Norris Cotton Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2009
Primary Completion (Actual)
March 1, 2013
Study Completion (Actual)
March 1, 2013
Study Registration Dates
First Submitted
May 20, 2009
First Submitted That Met QC Criteria
May 26, 2009
First Posted (Estimate)
May 27, 2009
Study Record Updates
Last Update Posted (Actual)
April 1, 2019
Last Update Submitted That Met QC Criteria
January 7, 2019
Last Verified
June 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D0906
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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