Trial Outcomes & Findings for Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue (NCT NCT00908791)
NCT ID: NCT00908791
Last Updated: 2019-04-01
Results Overview
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).
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Up to 28 days
Results posted on
2019-04-01
Participant Flow
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.
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.
Participant milestones
| Measure |
Conjugated Linoleic Acid
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
Baseline characteristics by cohort
| Measure |
Single Arm Study
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
|
Age, Continuous
|
57.36 years
STANDARD_DEVIATION 11.14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 28 daysTo 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).
Outcome measures
| Measure |
Pre CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
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
Spot 14 Expression Grade 1
|
10 participants
|
22 participants
|
—
|
—
|
|
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
Spot 14 Expression Grade 0
|
0 participants
|
0 participants
|
—
|
—
|
|
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
Spot 14 Expression Grade 2
|
14 participants
|
2 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentTo 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).
Outcome measures
| Measure |
Pre CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
FASN Expression Grade 0
|
0 participants
|
0 participants
|
—
|
—
|
|
Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
FASN Expression Grade 1
|
12 participants
|
14 participants
|
—
|
—
|
|
Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
FASN Expression Grade 2
|
12 participants
|
10 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentTo 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).
Outcome measures
| Measure |
Pre CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
LPL Expression Grade 0
|
4 participants
|
1 participants
|
—
|
—
|
|
Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
LPL Expression Grade 1
|
16 participants
|
20 participants
|
—
|
—
|
|
Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
LPL Expression Grade 2
|
4 participants
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentTo determine whether ≥ 10 days of CLA consumption impacts the status of tumor proliferation by calculating the percentage of cells expressing Ki67.
Outcome measures
| Measure |
Pre CLA
n=21 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
Increased expression from Baseline
|
5 Participants
|
—
|
—
|
—
|
|
Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
Decreased expression from Baseline
|
16 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentTo determine whether ≥ 10 days of CLA consumption impacts the status of tumor cell apoptosis by measuring the presence of immunostaining for cleaved caspase 3.
Outcome measures
| Measure |
Pre CLA
n=21 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
Mean # of Stained Cells Pre CLA
|
1.09 stained cells/field
Standard Deviation 0.34
|
—
|
—
|
—
|
|
Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
Mean # of Stained Cells Post CLA
|
1.32 stained cells/field
Standard Deviation 0.34
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentOutcome measures
| Measure |
Pre CLA
n=21 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
Post-treatment changes
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
Incremental changes over baseline
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
No correlation
|
21 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-CLA treatment and up to 2 years Post-CLA treatmentOutcome measures
| Measure |
Pre CLA
n=21 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
Post-treatment changes
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
Incremental changes over baseline
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
No correlation
|
21 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 monthsPopulation: Reported toxicities deemed
Outcome measures
| Measure |
Pre CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
Post CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 3 AEs Deemed "Possibly Related" to CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
# of Grade 4 AEs Deemed "Possibly Related" to CLA
n=24 Participants
Women with histologically proven invasive non-metastatic breast cancer.
|
|---|---|---|---|---|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Anorexia
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Constipation
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Diarrhea
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Fatigue
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Headache
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Heartburn
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Insomnia
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
Nausea
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Subjects Taking 1 or More Doses of CLA
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Subjects Taking 1 or More Doses of CLA
n=24 participants at risk
Women with histologically proven invasive, non metastatic breast cancer who received at least one day of CLA.
|
|---|---|
|
Nervous system disorders
abdominal pain
|
4.2%
1/24 • Number of events 5 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Skin and subcutaneous tissue disorders
alopecia
|
4.2%
1/24 • Number of events 3 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Gastrointestinal disorders
Anorexia
|
4.2%
1/24 • Number of events 11 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Psychiatric disorders
anxiety
|
4.2%
1/24 • Number of events 1 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Gastrointestinal disorders
constipation
|
8.3%
2/24 • Number of events 11 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
2/24 • Number of events 11 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Blood and lymphatic system disorders
Edema - limbs
|
4.2%
1/24 • Number of events 2 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
General disorders
Fatigue
|
12.5%
3/24 • Number of events 7 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Nervous system disorders
Headache
|
8.3%
2/24 • Number of events 5 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Gastrointestinal disorders
Heartburn
|
8.3%
2/24 • Number of events 11 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
General disorders
insomnia
|
16.7%
4/24 • Number of events 7 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
4/24 • Number of events 11 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Cardiac disorders
Palpitations
|
4.2%
1/24 • Number of events 1 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Nervous system disorders
Peripheral Neuropathy
|
8.3%
2/24 • Number of events 5 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.2%
1/24 • Number of events 3 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Injury, poisoning and procedural complications
Seroma
|
8.3%
2/24 • Number of events 2 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Blood and lymphatic system disorders
Elevated WBC
|
4.2%
1/24 • Number of events 2 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Infections and infestations
Skin Infection
|
8.3%
2/24 • Number of events 2 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
|
Skin and subcutaneous tissue disorders
Ulceration
|
4.2%
1/24 • Number of events 3 • 3 months
maximum allowed time frames include 4 weeks for screening, 28 days for study drug,and 4 weeks of follow up.
|
Additional Information
Burton Eisenberg, MD, Deputy Director, Norris Cotton Cancer Center
Norris Cotton Cancer Center
Phone: 603-653-3613
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place