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

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ClinicalTrials.gov Identifier: NCT00908791
Recruitment Status : Completed
First Posted : May 27, 2009
Results First Posted : April 1, 2019
Last Update Posted : April 1, 2019
Sponsor:
Collaborator:
Dartmouth College
Information provided by (Responsible Party):
Lionel.D.Lewis, MD, Dartmouth-Hitchcock Medical Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Breast Cancer
Intervention Drug: Conjugated Linoleic Acid (CLA)
Enrollment 24
Recruitment Details Women with invasive breast cancer were recruited from the Breast Oncology Clinic at the Norris Cotton Cancer Center at the Geisel School of Medicine at Dartmouth from June 2009 to March 2011. All patients gave written informed consent before entry into the study.
Pre-assignment Details Participants must have been able to take the study drug for a minimum of 10 days prior to tumor resection. For some potential participants the surgery date was scheduled earlier than 10 days and the study drug was not dispensed.
Arm/Group Title Conjugated Linoleic Acid
Hide Arm/Group Description Women with histologically proven invasive non-metastatic breast cancer.
Period Title: Overall Study
Started 24
Completed 24
Not Completed 0
Arm/Group Title Single Arm Study
Hide Arm/Group Description Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
24 women completed study treatments. Not all tumors yeiled data for secondary endpoints.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
  62.5%
>=65 years
9
  37.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
57.36  (11.14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
24
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
1.Primary Outcome
Title 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
Hide Description 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).
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre CLA Post CLA
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 24 24
Measure Type: Number
Unit of Measure: participants
Spot 14 Expression Grade 0 0 0
Spot 14 Expression Grade 1 10 22
Spot 14 Expression Grade 2 14 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pre CLA, Post CLA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method McNemar
Comments exact McNemar test for paired binary data.
2.Secondary Outcome
Title Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
Hide Description 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).
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre CLA Post CLA
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 24 24
Measure Type: Number
Unit of Measure: participants
FASN Expression Grade 0 0 0
FASN Expression Grade 1 12 14
FASN Expression Grade 2 12 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pre CLA, Post CLA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method McNemar
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
Hide Description 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).
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre CLA Post CLA
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 24 24
Measure Type: Number
Unit of Measure: participants
LPL Expression Grade 0 4 1
LPL Expression Grade 1 16 20
LPL Expression Grade 2 4 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pre CLA, Post CLA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method bowker's test of symmetry
Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
Hide Description To determine whether ≥ 10 days of CLA consumption impacts the status of tumor proliferation by calculating the percentage of cells expressing Ki67.
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Study Participants
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Increased expression from Baseline
5
  23.8%
Decreased expression from Baseline
16
  76.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Study Participants
Comments The Sign-Rank test for paired data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Sign test
Comments [Not Specified]
5.Secondary Outcome
Title Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
Hide Description 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.
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean # of Stained Cells Per Microscope Field Pre CLA
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 21
Mean (Standard Deviation)
Unit of Measure: stained cells/field
Mean # of Stained Cells Pre CLA 1.09  (0.34)
Mean # of Stained Cells Post CLA 1.32  (0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mean # of Stained Cells Per Microscope Field Pre CLA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
Hide Description [Not Specified]
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Correlation of CLA Isomers Matched to Spot 14 Expression
Hide Arm/Group Description:
Number of participants demonstrating a change in concentrations of CLA isomers in correlation to Spot 14 expression.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Post-treatment changes
0
   0.0%
Incremental changes over baseline
0
   0.0%
No correlation
21
 100.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Correlation of CLA Isomers Matched to Spot 14 Expression
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Other
Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
Hide Description [Not Specified]
Time Frame Pre-CLA treatment and up to 2 years Post-CLA treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Correlation of CLA Isomers Matched to Ki-67 Expression
Hide Arm/Group Description:
Number of participants demonstrating a change in concentrations of CLA isomers in correlation to Ki-67 expression.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Post-treatment changes
0
   0.0%
Incremental changes over baseline
0
   0.0%
No correlation
21
 100.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Correlation of CLA Isomers Matched to Ki-67 Expression
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Other
Comments [Not Specified]
8.Secondary Outcome
Title Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Hide Description [Not Specified]
Time Frame 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
Reported toxicities deemed
Arm/Group Title # of Grade 1 AEs Deemed "Possibly Related" to CLA # of Grade 2 AEs Deemed "Possibly Related" to CLA # of Grade 3 AEs Deemed "Possibly Related" to CLA # of Grade 4 AEs Deemed "Possibly Related" to CLA
Hide Arm/Group Description:
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Women with histologically proven invasive non-metastatic breast cancer.
Overall Number of Participants Analyzed 24 24 24 24
Measure Type: Number
Unit of Measure: participants
Anorexia 1 0 0 0
Constipation 1 0 0 0
Diarrhea 1 0 0 0
Fatigue 2 0 0 0
Headache 1 0 0 0
Heartburn 1 0 0 0
Insomnia 1 0 0 0
Nausea 2 0 0 0
Time Frame 3 months
Adverse Event Reporting Description maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
 
Arm/Group Title Subjects Taking 1 or More Doses of CLA
Hide Arm/Group Description Women with histologically proven invasive, non metastatic breast cancer who received at least one day of CLA.
All-Cause Mortality
Subjects Taking 1 or More Doses of CLA
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Subjects Taking 1 or More Doses of CLA
Affected / at Risk (%) # Events
Total   0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Subjects Taking 1 or More Doses of CLA
Affected / at Risk (%) # Events
Total   14/24 (58.33%)    
Blood and lymphatic system disorders   
Edema - limbs * 1  1/24 (4.17%)  2
Elevated WBC * 1  1/24 (4.17%)  2
Cardiac disorders   
Palpitations * 1  1/24 (4.17%)  1
Gastrointestinal disorders   
Anorexia * 1  1/24 (4.17%)  11
constipation * 1  2/24 (8.33%)  11
Diarrhea * 1  2/24 (8.33%)  11
Heartburn * 1  2/24 (8.33%)  11
Nausea * 1  4/24 (16.67%)  11
General disorders   
Fatigue * 1  3/24 (12.50%)  7
insomnia * 1  4/24 (16.67%)  7
Infections and infestations   
Skin Infection * 1  2/24 (8.33%)  2
Injury, poisoning and procedural complications   
Seroma * 1  2/24 (8.33%)  2
Nervous system disorders   
abdominal pain  1  1/24 (4.17%)  5
Headache * 1  2/24 (8.33%)  5
Peripheral Neuropathy * 1  2/24 (8.33%)  5
Psychiatric disorders   
anxiety * 1  1/24 (4.17%)  1
Skin and subcutaneous tissue disorders   
alopecia * 1  1/24 (4.17%)  3
Rash * 1  1/24 (4.17%)  3
Ulceration * 1  1/24 (4.17%)  3
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Burton Eisenberg, MD, Deputy Director, Norris Cotton Cancer Center
Organization: Norris Cotton Cancer Center
Phone: 603-653-3613
Responsible Party: Lionel.D.Lewis, MD, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00908791     History of Changes
Other Study ID Numbers: D0906
First Submitted: May 20, 2009
First Posted: May 27, 2009
Results First Submitted: July 14, 2014
Results First Posted: April 1, 2019
Last Update Posted: April 1, 2019