Trial Outcomes & Findings for Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer (NCT NCT00468910)
NCT ID: NCT00468910
Last Updated: 2017-05-31
Results Overview
Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. SPEC characterizes the size distribution of macromolecular complexes and other intracellular structures, with a decrease of the spectral slope implying a shift of the size distribution of intracellular structures toward smaller sizes. Spectral markers SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture.
COMPLETED
PHASE2
79 participants
3 months from baseline colonoscopy to end of intervention.
2017-05-31
Participant Flow
The study opened to accrual 02/22/2007 and closed to accrual 08/10/2009. Subjects were recruited at Northwestern University and University of Chicago.
A total of 110 subjects met the clinical definition of high risk for colorectal cancer, were entered onto the trial, and underwent initial spectral analysis. Of these, 81 had a cancer-associated spectral signature in histologically normal colonic mucosa.79 of these 81 subjects were randomized and began the study intervention
Participant milestones
| Measure |
Acetylsalicylic Acid
Patients receive oral acetylsalicylic acid (aspirin) once daily.
|
Placebo
Patients receive oral placebo once daily.
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
39
|
|
Overall Study
Randomization
|
40
|
39
|
|
Overall Study
Treatment
|
36
|
36
|
|
Overall Study
Post-Treatment Biopsy
|
36
|
36
|
|
Overall Study
Follow-up
|
36
|
36
|
|
Overall Study
COMPLETED
|
36
|
36
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
Reasons for withdrawal
| Measure |
Acetylsalicylic Acid
Patients receive oral acetylsalicylic acid (aspirin) once daily.
|
Placebo
Patients receive oral placebo once daily.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Medical Contraindication
|
0
|
1
|
Baseline Characteristics
Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Acetylsalicylic Acid
n=40 Participants
Patients receive oral acetylsalicylic acid (aspirin) once daily.
|
Placebo
n=39 Participants
Patients receive oral placebo once daily.
|
Total
n=79 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
37 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. SPEC characterizes the size distribution of macromolecular complexes and other intracellular structures, with a decrease of the spectral slope implying a shift of the size distribution of intracellular structures toward smaller sizes. Spectral markers SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture.
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
Baseline
|
40.72 micron^-1
Standard Deviation 16.91
|
37.54 micron^-1
Standard Deviation 21.64
|
|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
Post Intervention
|
43.45 micron^-1
Standard Deviation 26.84
|
37.52 micron^-1
Standard Deviation 28.15
|
PRIMARY outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa
Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. FRAC characterizes the spatial autocorrelation function of mass density distribution in tissue. SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
Baseline
|
142.41 unitless
Standard Deviation 2570.86
|
23.28 unitless
Standard Deviation 2699.82
|
|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
Post Intervention
|
-407.78 unitless
Standard Deviation 3470.69
|
650.97 unitless
Standard Deviation 3201.77
|
SECONDARY outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of cleaved caspase 3 .These were performed on samples that had been previously analyzed for 4D-ELF.
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
Baseline
|
4.56 Percentage of Total Cells
Standard Deviation 4.27
|
5.24 Percentage of Total Cells
Standard Deviation 3.69
|
|
Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
At 3 Months
|
4.26 Percentage of Total Cells
Standard Deviation 4.44
|
7.26 Percentage of Total Cells
Standard Deviation 6.77
|
SECONDARY outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of Ki-67. These were performed on samples that had been previously analyzed for 4D-ELF.
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
Baseline
|
38.07 Percentage of Total Cells
Standard Deviation 16.83
|
40.45 Percentage of Total Cells
Standard Deviation 12.26
|
|
Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
3 Months Intervention
|
43.60 Percentage of Total Cells
Standard Deviation 14.77
|
37.74 Percentage of Total Cells
Standard Deviation 13.37
|
SECONDARY outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Evaluate the effect of aspirin on rectal prostaglandin levels.
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Rectal Prostaglandin Levels as Measured by ELISA
Baseline
|
305.93 pg/ml
Standard Deviation 300.01
|
654.64 pg/ml
Standard Deviation 1536.52
|
|
Rectal Prostaglandin Levels as Measured by ELISA
Post Intervention
|
211.97 pg/ml
Standard Deviation 134.32
|
209.02 pg/ml
Standard Deviation 134.33
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 months from baseline colonoscopy to end of intervention.Population: Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa.
Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay.
Outcome measures
| Measure |
Acetylsalicylic Acid
n=36 Participants
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily.
|
Placebo
n=36 Participants
Patients receive oral placebo once daily.
|
|---|---|---|
|
Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
Baseline
|
712976.73 pg/ml
Standard Deviation 2082413.36
|
430109.56 pg/ml
Standard Deviation 798782.31
|
|
Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
Post Intervention
|
6914.87 pg/ml
Standard Deviation 20891.41
|
200233.5 pg/ml
Standard Deviation 463029.1
|
Adverse Events
Acetylsalicylic Acid
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Acetylsalicylic Acid
n=40 participants at risk
Patients receive oral acetylsalicylic acid (aspirin) once daily.
acetylsalicylic acid: Given orally
laboratory biomarker analysis: Correlative study
|
Placebo
n=39 participants at risk
Patients receive oral placebo once daily.
placebo: Given orally
laboratory biomarker analysis: Correlative study
|
|---|---|---|
|
Blood and lymphatic system disorders
Blood/Bone Marrow: Hemoglobin
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 3 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow: Other
|
2.5%
1/40 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Blood and lymphatic system disorders
Hemorrhage with Surgery
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Cardiac disorders
Hypertension
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Gastrointestinal disorders
Diarrhea
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Gastrointestinal disorders
Nausea
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Gastrointestinal disorders
Heartburn
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Stomach
|
5.0%
2/40 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
5.1%
2/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Abdomen Nos
|
5.0%
2/40 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Head/Headache
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
10.3%
4/39 • Number of events 4 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Other
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Joint
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Extremity - Limb
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Pain: Uterus
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Constitutional Symptoms: Fever
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Constitutional Symptoms: Insomnia
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Gastrointestinal disorders
Constitutional Symptoms: Weight Gain
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
General disorders
Constitutional Symptoms: Other
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Immune system disorders
Rhinitis
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Infections and infestations
Upper Airway Nos
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
5.1%
2/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Infections and infestations
Infection - Other
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
5.1%
2/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Metabolism and nutrition disorders
Metabolic/Lab - Other
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Metabolism and nutrition disorders
AST
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Metabolism and nutrition disorders
ALT
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
0.00%
0/39 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
5.1%
2/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Renal and urinary disorders
Cystitis
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 2 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Reproductive system and breast disorders
Sexual - Other
|
0.00%
0/40 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.5%
1/40 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
2.6%
1/39 • Number of events 1 • 3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60