Breast CancerEarly Phase 1NCT00908791
Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
A Early Phase 1 study testing Conjugated Linoleic Acid (CLA) in people with Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Conjugated Linoleic Acid (CLA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to Mar 2013
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756
About this study
Official title: 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.
- Conditions
- Breast Cancer
- Being tested
- Conjugated Linoleic Acid (CLA)
- Keywords
- Conjugated Linoleic Acid, Proof of Principle, Lipogenic Pathway, Clarinol
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conjugated Linoleic Acid (CLA)Drug
Also called Clarinol
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.
| Study group | Role | What they receive |
|---|---|---|
| CLA | Experimental | open-label, single-institution proof of principle study of oral CLA in patients with newly diagnosed adenocarcinoma of the breast. Receives: Drug: Conjugated Linoleic Acid (CLA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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).
Measured: Up to 28 days
Secondary outcomes (7)
Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
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).
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
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).
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
To determine whether ≥ 10 days of CLA consumption impacts the status of tumor proliferation by calculating the percentage of cells expressing Ki67.
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
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.
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
Measured: Pre-CLA treatment and up to 2 years Post-CLA treatment
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2009 (estimated)
- Study startJun 2009
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dartmouth College
- Responsible party
- Principal investigator, Lionel.D.Lewis, MD, Dartmouth-Hitchcock Medical Center
- Investigators
- Burton L Eisenberg, MD, Principal investigator, Norris Cotton Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00908791
- Sponsor's protocol ID
- D0906
- Status last verified
- Jun 2018
- First submitted
- 20 May 2009
- Last updated
- 1 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00908791
- Acronym / sponsor ID
- D0906
- Conditions
- Breast Cancer
- Keywords
- Conjugated Linoleic Acid, Proof of Principle, Lipogenic Pathway, Clarinol
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- Dartmouth College
- Study start
- Jun 2009 (actual)
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 27 May 2009 (estimated)
- Results
- Posted 1 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CLA | Experimental | Drug: Conjugated Linoleic Acid (CLA)open-label, single-institution proof of principle study of oral CLA in patients with newly diagnosed adenocarcinoma of the breast. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conjugated Linoleic Acid (CLA)Also: ClarinolConjugated 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. | Drug | CLA |
Primary outcome
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
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).
7 secondary outcomes
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
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
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
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
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
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
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Time frame: 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Burton L Eisenberg, MD principal investigator
Norris Cotton Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Conjugated Linoleic Acid (CLA) in people with Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
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 4 inclusion and 5 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 1 Apr 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 United States. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2019.