- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00468910
Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer
Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. Determine whether acetylsalicylic acid (aspirin) will alter spectral markers (i.e., spectral slope and fractal dimension) in distal colonic mucosa of patients who are at increased risk for the development or recurrence of colorectal cancer.
SECONDARY OBJECTIVES:
I. Assess the effect of this drug on colonic epithelial apoptosis and cell proliferation in these patients.
II. Assess the effect of this drug on rectal prostaglandin levels in these patients.
III. Assess the effect of this drug on platelet cyclooxygenase activity in these patients.
IV. Correlate changes in spectral markers with UGT1A6 genotype in patients treated with this drug.
OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified by clinical site and adenoma/carcinoma maximal size. Patients with abnormal spectral biomarkers are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral acetylsalicylic acid (aspirin) once daily.
ARM II: Patients receive oral placebo once daily.
In both arms, treatment continues for 3 months in the absence of unacceptable toxicity.
Patients undergo flexible sigmoidoscopy and biopsies as well as blood collection at baseline (during prestudy colonoscopy) and at completion of study treatment for comparison of spectral signatures with biomarkers of both aspirin activity (including plasma cyclooxygenase activity and rectal prostaglandin levels) as well as with biomarkers associated with antineoplastic alteration (including apoptosis and cell proliferation). UGT1A6 genotyping analysis is also performed.
After completion of study treatment, patients are followed at 3 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Northwestern University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Criteria:
- No active or metastatic cancer within the past 6 months
- Scheduled to undergo colonoscopy for colonic neoplasia surveillance
- Hemoglobin >= 12.0 g/dL
- Platelet count >= 120,000/mm^3
- AST or ALT =< 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase =< 1.5 times ULN
- Bilirubin =< 1.5 times ULN
- BUN =< 40 mg/dL
- Glomerular filtration rate >= 45 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No coagulopathy
- No anemia
- No history of peptic ulcer disease or gastrointestinal hemorrhage
- No history of cerebrovascular accident
- No uncontrolled hypertension
- No history of intolerance or allergy to aspirin or to NSAIDs
- No liver disease as manifested by signs or symptoms of cirrhosis
- No endoscopic or radiographic evidence of portal hypertension
- No active colitis by endoscopy
- No history of inflammatory bowel disease
- No requirement for aspirin as medical therapy (i.e., post-myocardial infarction or transient ischemic attack)
- No untreated helicobacter pylori infection
History of significant colonic neoplasia, defined as 1 of the following:
- Adenoma within the past 6 years
- Colorectal cancer within the past 6 years
- Known adenoma on present exam
- Histologically confirmed polyps seen on imaging
- INR =< 1.5
- At least 6 months since prior cancer treatment
- No other concurrent acetylsalicylic acid (aspirin)-containing products or non-steroidal anti-inflammatory drugs (NSAIDs)
- No concurrent systemic corticosteroids
- No other concurrent anticoagulants or antiplatelet agents
- No concurrent investigational drugs
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I
Patients receive oral acetylsalicylic acid (aspirin) once daily.
|
Correlative study
Given orally
Other Names:
|
Placebo Comparator: Arm II
Patients receive oral placebo once daily.
|
Correlative study
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months.
Time Frame: 3 months from baseline colonoscopy to end of intervention.
|
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. |
3 months from baseline colonoscopy to end of intervention.
|
Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months.
Time Frame: 3 months from baseline colonoscopy to end of intervention.
|
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 |
3 months from baseline colonoscopy to end of intervention.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3
Time Frame: 3 months from baseline colonoscopy to end of intervention.
|
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.
|
3 months from baseline colonoscopy to end of intervention.
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Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67
Time Frame: 3 months from baseline colonoscopy to end of intervention.
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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.
|
3 months from baseline colonoscopy to end of intervention.
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Rectal Prostaglandin Levels as Measured by ELISA
Time Frame: 3 months from baseline colonoscopy to end of intervention.
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Evaluate the effect of aspirin on rectal prostaglandin levels.
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3 months from baseline colonoscopy to end of intervention.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay
Time Frame: 3 months from baseline colonoscopy to end of intervention.
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Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay.
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3 months from baseline colonoscopy to end of intervention.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hemant Roy, Northwestern University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Precancerous Conditions
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Aspirin
Other Study ID Numbers
- NCI-2009-00841 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- N01CN35157 (U.S. NIH Grant/Contract)
- CDR0000652929
- NCI 04-2-03 (Other Identifier: Northwestern University)
- NWU04-2-03 (Other Identifier: DCP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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