Trial Outcomes & Findings for ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension (NCT NCT05056896)

NCT ID: NCT05056896

Last Updated: 2026-05-15

Results Overview

All patients with available pre- and post-treatment samples containing high-quality RNA sequencing reads from at least 1,000 EPCAM+ single cells per time point were included in the analysis. Single cells were clustered according to cell type. The proportion (%) of cells expressing LGR5 (LGR5+), an accepted intestinal stem cell (ISC) marker of cell stemness, among the ISC cluster was calculated for each participant at each time point. The change in proportion of LGR5+ ISCs within each individual in post-treatment samples from pre-treatment samples was calculated.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

EARLY_PHASE1

Target enrollment

161 participants

Primary outcome timeframe

2 months

Results posted on

2026-05-15

Participant Flow

Potentially eligible patients were contacted by letter or directly approached by a treating physician if they were identified as having a recent history of colorectal adenoma by their treating physician or via natural language processing searches of the pathology database at Mass General Brigham. If no response to the letter is received, participants are contacted by phone (unless they have otherwise opted out) by a member of the study team. If interested, they are then screened for eligibility

Participants are screened for eligibility criteria by a member of the study staff and provide written informed consent prior to any research activities. Eligible and consented participants are stratified according to age group: younger (18-55 years of age) or older (65+ years of age), prior to randomization.

Participant milestones

Participant milestones
Measure
Adults 18-55 Years of Age Randomized to Low Dose Aspirin
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Adults 18-55 Years of Age Randomized to Placebo
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to placebo and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Adults 65+ Years of Age Randomized to Low Dose Aspirin
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Older: Adults 65+ Years of Age or Older Randomized to Placebo
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to placebo and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Overall Study
STARTED
40
40
41
40
Overall Study
COMPLETED
34
39
37
39
Overall Study
NOT COMPLETED
6
1
4
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Low Dose Aspirin
n=81 Participants
Participants will be randomly assigned to aspirin group and receive a daily low dose aspirin (81 mg) for the duration of the study up to 12 weeks. Aspirin: Capsule taken orally
Placebo
n=80 Participants
Participants will be randomly assigned to placebo group and receive a daily placebo capsule for the duration of the study up to 12 weeks. Placebo: Capsule taken orally
Total
n=161 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Age, Categorical
Between 18 and 65 years
40 Participants
n=11 Participants
40 Participants
n=9 Participants
80 Participants
n=20 Participants
Age, Categorical
>=65 years
41 Participants
n=11 Participants
40 Participants
n=9 Participants
81 Participants
n=20 Participants
Age, Continuous
60 years
n=11 Participants
59.7 years
n=9 Participants
59.85093168 years
n=20 Participants
Sex: Female, Male
Female
45 Participants
n=11 Participants
40 Participants
n=9 Participants
85 Participants
n=20 Participants
Sex: Female, Male
Male
36 Participants
n=11 Participants
40 Participants
n=9 Participants
76 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
7 Participants
n=11 Participants
6 Participants
n=9 Participants
13 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
73 Participants
n=11 Participants
74 Participants
n=9 Participants
147 Participants
n=20 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=11 Participants
0 Participants
n=9 Participants
1 Participants
n=20 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Race (NIH/OMB)
Asian
4 Participants
n=11 Participants
3 Participants
n=9 Participants
7 Participants
n=20 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=11 Participants
0 Participants
n=9 Participants
0 Participants
n=20 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=11 Participants
2 Participants
n=9 Participants
3 Participants
n=20 Participants
Race (NIH/OMB)
White
72 Participants
n=11 Participants
73 Participants
n=9 Participants
145 Participants
n=20 Participants
Race (NIH/OMB)
More than one race
2 Participants
n=11 Participants
1 Participants
n=9 Participants
3 Participants
n=20 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=11 Participants
1 Participants
n=9 Participants
3 Participants
n=20 Participants
Region of Enrollment
United States
81 participants
n=11 Participants
80 participants
n=9 Participants
161 participants
n=20 Participants
BMI
27.17 kg/m^2
n=11 Participants
27.8615461 kg/m^2
n=9 Participants
27.5129332 kg/m^2
n=20 Participants

PRIMARY outcome

Timeframe: 2 months

Population: The primary outcome analysis was performed in 25 individuals who had available single-cell RNA sequencing data from at least 1,000 high quality EPCAM+ cells at both the pre- and post-treatment timepoint. This is a subset of the total study population. Randomization is preserved among those remaining in the final analysis and they are representative of the final study population. Future analyses will validate positive primary findings in the remaining study population using correlative approaches

All patients with available pre- and post-treatment samples containing high-quality RNA sequencing reads from at least 1,000 EPCAM+ single cells per time point were included in the analysis. Single cells were clustered according to cell type. The proportion (%) of cells expressing LGR5 (LGR5+), an accepted intestinal stem cell (ISC) marker of cell stemness, among the ISC cluster was calculated for each participant at each time point. The change in proportion of LGR5+ ISCs within each individual in post-treatment samples from pre-treatment samples was calculated.

Outcome measures

Outcome measures
Measure
Adults 18-55 Years of Age Randomized to Low Dose Aspirin
n=5 Participants
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Adults 18-55 Years of Age Randomized to Placebo
n=7 Participants
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to placebon and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Adults 65+ Years of Age Randomized to Low Dose Aspirin
n=7 Participants
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Adults 65 Years of Age or Older Randomized to Placebo
n=6 Participants
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to placebo and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Change of Intestinal Stem Cell Marker Gene Expression
3.4 Percent Change of LGR5+ Stem Cells
Standard Deviation 7.6
-9.1 Percent Change of LGR5+ Stem Cells
Standard Deviation 7.0
-0.36 Percent Change of LGR5+ Stem Cells
Standard Deviation 12.2
6.4 Percent Change of LGR5+ Stem Cells
Standard Deviation 5.1

SECONDARY outcome

Timeframe: 2 months

Comparing change in PGE-M between treatment groups (aspirin and placebo) using a two-sample t-test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months

Comparing change inGDF-15 between aspirin and placebo groups, using a two-sample t-test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months

Analysis of the ChIP-seq data (\>60 million reads, 50-bp paired end) using the publicly available Cistrome Analysis Pipeline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months

RNA-seq sequence data (\> 50 million reads) will be mapped to hg19 through use of TopHat2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 months

Aspirin use and dose will be associated with microbial operational taxonomic units (OTUs) using the Biobakery3 computational analysis pipeline.

Outcome measures

Outcome data not reported

Adverse Events

Adults 18-55 Years of Age Randomized to Low Dose Aspirin

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

Adults 18-55 Years of Age Randomized to Placebo

Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths

Adults 65+ Years of Age Randomized to Low Dose Aspirin

Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths

Adults 65 Years of Age or Older Randomized to Placebo

Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Adults 18-55 Years of Age Randomized to Low Dose Aspirin
n=40 participants at risk
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Adults 18-55 Years of Age Randomized to Placebo
n=40 participants at risk
Participants are stratified according to age group prior to randomization. These participants are adults between 18 and 55 years of age and randomized to placebon and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Adults 65+ Years of Age Randomized to Low Dose Aspirin
n=41 participants at risk
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to Low Dose Aspirin and receive blinded capsules containing 81 mg of aspirin to be taken daily for at least 8 weeks.
Adults 65 Years of Age or Older Randomized to Placebo
n=40 participants at risk
Participants are stratified according to age group prior to randomization. These participants are adults 65+ years of age and randomized to placebo and receive blinded capsules containing placebo to be taken daily for at least 8 weeks.
Injury, poisoning and procedural complications
Rotator Cuff injury
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Infections and infestations
Wound infection
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
Skin and subcutaneous tissue disorders
Dog Bite
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Gastroesophageal reflux disease
2.5%
1/40 • 3 months
2.5%
1/40 • 3 months
2.4%
1/41 • 3 months
2.5%
1/40 • 3 months
Gastrointestinal disorders
Nausea
2.5%
1/40 • 3 months
5.0%
2/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
General disorders
Fatigue
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
2.5%
1/40 • 3 months
General disorders
Fever
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
5.0%
2/40 • 3 months
Renal and urinary disorders
Urinary Tract Infection
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
5.0%
2/40 • 3 months
Gastrointestinal disorders
Bloating
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
2.5%
1/40 • 3 months
Gastrointestinal disorders
Constipation
2.5%
1/40 • 3 months
2.5%
1/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/40 • 3 months
2.5%
1/40 • 3 months
4.9%
2/41 • 3 months
0.00%
0/40 • 3 months
Nervous system disorders
Dizziness
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/40 • 3 months
2.5%
1/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
General disorders
Pain
5.0%
2/40 • 3 months
7.5%
3/40 • 3 months
4.9%
2/41 • 3 months
10.0%
4/40 • 3 months
Psychiatric disorders
Psychiatric disorders, other
0.00%
0/40 • 3 months
2.5%
1/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Rectal Hemorrhage
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
Ear and labyrinth disorders
Ear and labyrinth disorders, other
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
4.9%
2/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Flatulence
0.00%
0/40 • 3 months
2.5%
1/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
Skin and subcutaneous tissue disorders
Urticaria
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
Ear and labyrinth disorders
Vertigo
0.00%
0/40 • 3 months
5.0%
2/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Investigations
Weight gain
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
5.0%
2/40 • 3 months
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
0.00%
0/40 • 3 months
2.5%
1/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Musculoskeletal and connective tissue disorders
Arthritis
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Eye disorders
Conjunctivitis infective
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Dysphagia
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Enterocolitis
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
General disorders
Generalized Edema
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
2.5%
1/40 • 3 months
Ear and labyrinth disorders
Hearing impaired
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Skin and subcutaneous tissue disorders
Hematoma
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Musculoskeletal and connective tissue disorders
Hip Fracture
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Metabolism and nutrition disorders
Hyperglycemia
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Vascular disorders
Hypertension
0.00%
0/40 • 3 months
0.00%
0/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Reproductive system and breast disorders
Menorrhagia
2.5%
1/40 • 3 months
0.00%
0/40 • 3 months
0.00%
0/41 • 3 months
0.00%
0/40 • 3 months
Gastrointestinal disorders
Diarrhea
0.00%
0/40 • 3 months
5.0%
2/40 • 3 months
9.8%
4/41 • 3 months
2.5%
1/40 • 3 months
Nervous system disorders
Headache
7.5%
3/40 • 3 months
5.0%
2/40 • 3 months
2.4%
1/41 • 3 months
0.00%
0/40 • 3 months
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
0.00%
0/40 • 3 months
5.0%
2/40 • 3 months
4.9%
2/41 • 3 months
5.0%
2/40 • 3 months
Infections and infestations
Flu like symptoms
20.0%
8/40 • 3 months
15.0%
6/40 • 3 months
9.8%
4/41 • 3 months
17.5%
7/40 • 3 months
Infections and infestations
Infections and infestations - other, specify
7.5%
3/40 • 3 months
2.5%
1/40 • 3 months
12.2%
5/41 • 3 months
5.0%
2/40 • 3 months

Additional Information

Marina Magicheva-Gupta

Massachusetts General Hospital

Phone: 617 726 2426

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place