ASPIRED: ASPirin Intervention for the REDuction of Colorectal Cancer Risk

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02394769
Collaborator
National Cancer Institute (NCI) (NIH)
180
Enrollment
1
Location
3
Arms
167.9
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study is investigating the use of aspirin as a potential chemopreventive agent to reduce risk of colorectal cancer

Condition or DiseaseIntervention/TreatmentPhase
N/A

Detailed Description

This research study, is investigating the use of aspirin as a potential chemopreventive agent to reduce risk of colorectal cancer. Within the gastroenterology practice of Massachusetts General Hospital (MGH), we will conduct a prospective, double-blind, placebo-controlled, randomized clinical trial to measure the effects of daily low-dose (81 mg/day) and standard-dose (325 mg/day) aspirin on urine, plasma, stool, and tissue biomarkers associated with colorectal cancer.

Aspirin is part of the non-steroidal anti-inflammatory drug (NSAID) family, which are drugs routinely used for their pain-killing (analgesic), fever-reducing (antipyretic), or anti-inflammatory properties. Most NSAIDs are available as over-the-counter formulations. Substantial evidence has conclusively demonstrated that aspirin reduces the risk of colorectal neoplasia, yet there remains uncertainty surrounding its mode of action. Aspirin has already been established to reduce the risk of cardiovascular disease. Prospective studies as well as randomized clinical trials demonstrate that aspirin reduces the risk of precancerous polyps and colorectal cancer.

Study Design

Study Type:
Interventional
Actual Enrollment :
180 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
ASPIRED: ASPirin Intervention for the REDuction of Colorectal Cancer Risk
Actual Study Start Date :
Jul 6, 2015
Actual Primary Completion Date :
Apr 11, 2019
Anticipated Study Completion Date :
Jul 1, 2029

Arms and Interventions

ArmIntervention/Treatment
Placebo Comparator: Placebo (For Aspirin)

The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks.

Drug: Placebo for Aspirin

Active Comparator: Low Dose Aspirin

The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks.

Drug: Aspirin
Other Names:
  • 2-Acetylsalicylic Acid
  • ASA
  • Active Comparator: Standard Dose Aspirin

    The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks.

    Drug: Aspirin
    Other Names:
  • 2-Acetylsalicylic Acid
  • ASA
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Urinary Prostaglandin Metabolites (PGE-M) [8-12 weeks]

      Measured using liquid chromatography/mass spectrometry

    Secondary Outcome Measures

    1. Plasma Macrophage Inhibitory Cytokine-1 (MIC-1), an Inflammatory Biomarker [8-12 weeks]

      Measured using an ELISA for MIC-1

    2. Chromatin Binding [8-12 weeks]

      Measured using ChIP-Seq of DNA extracted from colonic epithelium

    3. Expression of Wnt-associated Signaling Genes (CTNNB1, AXIN2 and MYC) [8-12 weeks]

      Measured using RNA-seq of colonic epithelium

    4. Spectral Biomarkers of Colorectal Cancer [8-12 weeks]

      Measured using Partial Wave Spectroscopy on rectal cytology brushing samples

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Underwent screening or surveillance colonoscopy at MGH within the last 9 months with removal of at least one adenoma.

    • Age 18-80 years.

    • This study will only include adult participants because colorectal carcinogenesis in children is more likely to be related to a cancer predisposition syndrome with distinct biological mechanisms compared with sporadic colorectal cancer in adults. Patients over age 80 will not be enrolled since the benefits and risks of a daily aspirin regimen over the age of 80 have not yet been well-characterized.

    • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

    • Not currently taking aspirin (any dose) within the last 6 months.

    • The effects of aspirin on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.

    • Ability to understand and the willingness to sign a written informed consent document.

    Exclusion Criteria:
    • Use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID) at any dose at least three times a week during the two months prior to randomization.

    • Diagnosis of inflammatory bowel disease, liver or kidney disease, bleeding diathesis

    • Any prior diagnosis of gastrointestinal cancer (including esophageal, small intestine, colon, pancreatic), or any diagnosis of other cancers (with the exception of non- melanoma skin) in which there has been any active treatment within the last three years

    • Participants who are receiving any other investigational agents.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to aspirin.

    • Known diagnosis of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch Syndrome).

    • Any adenoma that was not completely removed during previous colonoscopy.

    • History of aspirin intolerance, bleeding diathesis, peptic ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to colonoscopy.

    • Inability or unwillingness to abstain from non-protocol use of aspirin or NSAIDs or to provide blood, urine, or stool samples or colon biopsies during the study.

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    • Pregnant or breastfeeding.

    • Pregnant women are excluded from this study because aspirin is an FDA Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with aspirin, breastfeeding should be discontinued if the mother is treated with aspirin.

    • Participant must be able to swallow pills.

    • Participant is taking any anticoagulant agent (e.g. warfarin) or antiplatelet agent (e.g. clopidogrel).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Massachusetts General HospitalBostonMassachusettsUnited States02114

    Sponsors and Collaborators

    • Massachusetts General Hospital
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Andrew T Chan, MD, MPH, Massachusetts General Hospital

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Andrew T. Chan, MD, MPH, Principal Investigator, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT02394769
    Other Study ID Numbers:
    • 14-496
    • R01CA137178
    First Posted:
    Mar 20, 2015
    Last Update Posted:
    Mar 23, 2021
    Last Verified:
    Feb 1, 2021
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Andrew T. Chan, MD, MPH, Principal Investigator, Massachusetts General Hospital
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsPatients who meet the inclusion criteria will be identified through investigators during their routine clinical practice, supplemented by a periodic query of the MGH endoscopy and pathology databases. Potentially eligible participants are approached by letter from their treating physician. Two weeks after receiving the letter, study staff will contact eligible parties and screen for eligibility via phone interview. Enrollment began in July 2015 and ended in February 2019.
    Pre-assignment Detail
    Arm/Group TitlePlacebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Arm/Group DescriptionThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks. Placebo for AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. Aspirin
    Period Title: Overall Study
    STARTED606060
    COMPLETED585754
    NOT COMPLETED236

    Baseline Characteristics

    Arm/Group TitlePlacebo (For Aspirin)Low Dose AspirinStandard Dose AspirinTotal
    Arm/Group DescriptionThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks. Placebo for AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. AspirinTotal of all reporting groups
    Overall Participants606060180
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.1
    (9.2)
    56.1
    (8.7)
    57.5
    (8.3)
    56.9
    (8.7)
    Sex: Female, Male (Count of Participants)
    Female
    28
    46.7%
    29
    48.3%
    28
    46.7%
    85
    47.2%
    Male
    32
    53.3%
    31
    51.7%
    32
    53.3%
    95
    52.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    3.3%
    2
    3.3%
    1
    1.7%
    5
    2.8%
    Not Hispanic or Latino
    58
    96.7%
    58
    96.7%
    59
    98.3%
    175
    97.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.7%
    0
    0%
    2
    3.3%
    3
    1.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    5%
    4
    6.7%
    3
    5%
    10
    5.6%
    White
    55
    91.7%
    52
    86.7%
    53
    88.3%
    160
    88.9%
    More than one race
    0
    0%
    4
    6.7%
    2
    3.3%
    6
    3.3%
    Unknown or Not Reported
    1
    1.7%
    0
    0%
    0
    0%
    1
    0.6%
    Marital status (Count of Participants)
    Married
    40
    66.7%
    39
    65%
    37
    61.7%
    116
    64.4%
    Never married
    6
    10%
    12
    20%
    11
    18.3%
    29
    16.1%
    Separated
    2
    3.3%
    0
    0%
    1
    1.7%
    3
    1.7%
    Divorced
    8
    13.3%
    7
    11.7%
    7
    11.7%
    22
    12.2%
    Widowed
    4
    6.7%
    2
    3.3%
    4
    6.7%
    10
    5.6%
    Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m2]
    26.8
    (5.0)
    28.4
    (4.9)
    27.5
    (5.7)
    27.6
    (5.2)
    Body Mass Index, categories (Count of Participants)
    Normal, <18.5-24.9
    21
    35%
    16
    26.7%
    21
    35%
    58
    32.2%
    Overweight, 25.0-29.9
    26
    43.3%
    26
    43.3%
    23
    38.3%
    75
    41.7%
    Obese ≥30.0
    13
    21.7%
    18
    30%
    16
    26.7%
    47
    26.1%
    Smoking status (Count of Participants)
    Never
    38
    63.3%
    36
    60%
    32
    53.3%
    106
    58.9%
    Former
    18
    30%
    20
    33.3%
    19
    31.7%
    57
    31.7%
    Current
    4
    6.7%
    3
    5%
    8
    13.3%
    15
    8.3%
    Missing
    0
    0%
    1
    1.7%
    1
    1.7%
    2
    1.1%
    Alcohol consumption (Count of Participants)
    Never
    7
    11.7%
    11
    18.3%
    11
    18.3%
    29
    16.1%
    Rarely
    14
    23.3%
    16
    26.7%
    18
    30%
    48
    26.7%
    1-5 times/week
    29
    48.3%
    24
    40%
    23
    38.3%
    76
    42.2%
    Daily
    10
    16.7%
    8
    13.3%
    6
    10%
    24
    13.3%
    More than daily
    0
    0%
    1
    1.7%
    2
    3.3%
    3
    1.7%
    Personal cancer history, yes (Count of Participants)
    Count of Participants [Participants]
    10
    16.7%
    6
    10%
    4
    6.7%
    20
    11.1%
    Family history of colorectal cancer, yes (Count of Participants)
    Count of Participants [Participants]
    13
    21.7%
    10
    16.7%
    12
    20%
    35
    19.4%
    Type II diabetes, yes (Count of Participants)
    Count of Participants [Participants]
    2
    3.3%
    3
    5%
    2
    3.3%
    7
    3.9%
    Menopause status (participants) [Number]
    Premenopausal
    3
    5%
    9
    15%
    5
    8.3%
    17
    9.4%
    Perimenopausal
    4
    6.7%
    1
    1.7%
    2
    3.3%
    7
    3.9%
    Postmenopausal
    20
    33.3%
    17
    28.3%
    18
    30%
    55
    30.6%
    Missing
    1
    1.7%
    2
    3.3%
    3
    5%
    6
    3.3%
    History of 81 mg aspirin use (Count of Participants)
    Never
    55
    91.7%
    50
    83.3%
    53
    88.3%
    158
    87.8%
    Intermittently (<2x/week)
    2
    3.3%
    5
    8.3%
    5
    8.3%
    12
    6.7%
    Regularly (>2x/week)
    2
    3.3%
    2
    3.3%
    2
    3.3%
    6
    3.3%
    Missing
    1
    1.7%
    3
    5%
    0
    0%
    4
    2.2%
    History of 325 mg aspirin use (Count of Participants)
    Never
    40
    66.7%
    42
    70%
    42
    70%
    124
    68.9%
    Intermittently (<2x/week)
    17
    28.3%
    15
    25%
    17
    28.3%
    49
    27.2%
    Regularly (>2x/week)
    1
    1.7%
    1
    1.7%
    1
    1.7%
    3
    1.7%
    Missing
    2
    3.3%
    2
    3.3%
    0
    0%
    4
    2.2%
    History of non-steroidal anti-inflammatory drug use (Count of Participants)
    Never
    18
    30%
    13
    21.7%
    19
    31.7%
    50
    27.8%
    Intermittently (<2x/week)
    31
    51.7%
    36
    60%
    32
    53.3%
    99
    55%
    Regularly (>2x/week)
    10
    16.7%
    9
    15%
    8
    13.3%
    27
    15%
    Missing
    1
    1.7%
    2
    3.3%
    1
    1.7%
    4
    2.2%
    Proton pump inhibitor use (Count of Participants)
    Current and regular
    5
    8.3%
    6
    10%
    8
    13.3%
    19
    10.6%
    No, never regularly
    48
    80%
    49
    81.7%
    48
    80%
    145
    80.6%
    Missing
    7
    11.7%
    5
    8.3%
    4
    6.7%
    16
    8.9%
    H2-blocker use (Count of Participants)
    Current and regular
    2
    3.3%
    5
    8.3%
    2
    3.3%
    9
    5%
    No, never regularly
    56
    93.3%
    54
    90%
    57
    95%
    167
    92.8%
    Missing
    2
    3.3%
    1
    1.7%
    1
    1.7%
    4
    2.2%
    Antacid use (Count of Participants)
    Current and regular
    5
    8.3%
    3
    5%
    3
    5%
    11
    6.1%
    No, never regularly
    54
    90%
    57
    95%
    57
    95%
    168
    93.3%
    Missing
    1
    1.7%
    0
    0%
    0
    0%
    1
    0.6%
    Statin use (Count of Participants)
    Current and regular
    14
    23.3%
    11
    18.3%
    16
    26.7%
    41
    22.8%
    No, never regularly
    44
    73.3%
    48
    80%
    43
    71.7%
    135
    75%
    Missing
    2
    3.3%
    1
    1.7%
    1
    1.7%
    4
    2.2%

    Outcome Measures

    1. Primary Outcome
    TitleChange in Urinary Prostaglandin Metabolites (PGE-M)
    DescriptionMeasured using liquid chromatography/mass spectrometry
    Time Frame8-12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePlacebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Arm/Group DescriptionThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks. Placebo for AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. Aspirin
    Measure Participants585754
    Baseline urinary PGE-M
    15.5
    (12.6)
    17.7
    (17.1)
    14.3
    (13.7)
    Post-intervention urinary PGE-M
    16.4
    (15.8)
    13.1
    (13.4)
    9.4
    (7.9)
    Change in urinary PGE-M
    0.8
    (11.8)
    -4.6
    (17.7)
    -4.9
    (11.2)
    2. Secondary Outcome
    TitlePlasma Macrophage Inhibitory Cytokine-1 (MIC-1), an Inflammatory Biomarker
    DescriptionMeasured using an ELISA for MIC-1
    Time Frame8-12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleChromatin Binding
    DescriptionMeasured using ChIP-Seq of DNA extracted from colonic epithelium
    Time Frame8-12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleExpression of Wnt-associated Signaling Genes (CTNNB1, AXIN2 and MYC)
    DescriptionMeasured using RNA-seq of colonic epithelium
    Time Frame8-12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleSpectral Biomarkers of Colorectal Cancer
    DescriptionMeasured using Partial Wave Spectroscopy on rectal cytology brushing samples
    Time Frame8-12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame3 months
    Adverse Event Reporting Description
    Arm/Group TitlePlacebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Arm/Group DescriptionThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks. Placebo for AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. AspirinThe first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks. Aspirin
    All Cause Mortality
    Placebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/60 (0%) 0/60 (0%) 0/60 (0%)
    Serious Adverse Events
    Placebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/60 (0%) 0/60 (0%) 0/60 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo (For Aspirin)Low Dose AspirinStandard Dose Aspirin
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total14/60 (23.3%) 17/60 (28.3%) 17/60 (28.3%)
    Blood and lymphatic system disorders
    Extended bleeding/bruising0/60 (0%) 0/60 (0%) 2/60 (3.3%)
    Gastrointestinal disorders
    GI upset (i.e. heartburn/acid reflux/nausea/gas)4/60 (6.7%) 6/60 (10%) 3/60 (5%)
    Bleeding hemorrhoids0/60 (0%) 0/60 (0%) 1/60 (1.7%)
    Constipation0/60 (0%) 2/60 (3.3%) 1/60 (1.7%)
    General disorders
    Unrelated infection/cold symptoms/sinus related6/60 (10%) 5/60 (8.3%) 4/60 (6.7%)
    Seasonal allergies1/60 (1.7%) 2/60 (3.3%) 3/60 (5%)
    Fever1/60 (1.7%) 0/60 (0%) 2/60 (3.3%)
    Other, unrelated2/60 (3.3%) 1/60 (1.7%) 1/60 (1.7%)
    Nervous system disorders
    Headaches0/60 (0%) 1/60 (1.7%) 0/60 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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/TitleAndrew T. Chan, MD, MPH
    OrganizationMassachusetts General Hospital
    Phone(617) 726-3212
    Emailachan@partners.org
    Responsible Party:
    Andrew T. Chan, MD, MPH, Principal Investigator, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT02394769
    Other Study ID Numbers:
    • 14-496
    • R01CA137178
    First Posted:
    Mar 20, 2015
    Last Update Posted:
    Mar 23, 2021
    Last Verified:
    Feb 1, 2021