Effect of Aspirin on Gut Microbiome

NCT ID: NCT02761486

Last Updated: 2020-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-08-29

Brief Summary

Regular use of aspirin may reduce the incidence of colorectal cancer (CRC). However, it is unclear through which mechanism aspirin exerts its effect, in whom it decreases CRC risk and in whom it causes side effects. Recently, the imbalanced gut microbiome was linked to inflammation and CRC risk. The main hypothesis for this study is that aspirin may decrease CRC risk via targeting the gut microbiome. The study will be a randomized placebo-controlled double-blinded design, recruiting 50 healthy subjects, 50-75 years old, from the PRospective Evaluation of SEPTin 9 (PRESEPT) cohort living in the greater Twin Cities area, who will receive either aspirin or placebo for 6 weeks.

Detailed Description

The pilot study will evaluate the feasibility of conducting a large randomized trial and estimate the effects of aspirin on the gut microbiome. The study will recruit 50 healthy subjects, 50-75 years old, from the PRospective Evaluation of SEPTin 9 (PRESEPT) cohort living in the greater Twin Cities area.

The Primary Aim is to estimate the impact of a 3- and 6-week intake of once daily 325 mg aspirin on the composition of the gut microbiome using a randomized placebo-controlled double-blinded design, i.e. examine the change of microbiome over time within and between the subjects. The hypothesis for this aim is that in the aspirin arm versus the placebo arm, gut microbiome composition will shift towards a lower proportion of pro-inflammatory, CRC-predisposing bacteria (e.g. Fusobacteria) and higher proportion of anti-inflammatory, CRC-protective bacteria (e.g. butyrate-producing bacteria).

The Secondary Aims are to examine the correlation between the aspirin-related changes in microbiome profile with the levels of circulating inflammatory biomarkers in urine and plasma. Within-individual and between-arm differences in microbiome composition will be compared after 3 and 6 weeks of aspirin intake. Also, the microbiome composition will be compared after 3-week and 6-week wash-out periods to test whether these periods are sufficient to restore gut microbiome composition to a pre-treatment level. This study will inform future crossover randomized studies focusing on CRC preventive interventions that will enable clinicians to identify optimal candidates for aspirin therapy for the purposes of CRC prevention using this accessible and cheap drug.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Aspirin

The subjects will receive 325 mg of aspirin once a day for 6 weeks followed by a 6-week washout.

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

325mg aspirin per day

Placebo

The subjects will receive placebo once a day for 6 weeks followed by a 6-week washout.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo in matching capsules

Interventions

Aspirin

325mg aspirin per day

Intervention Type: DRUG

Placebo

placebo in matching capsules

Intervention Type: DRUG

Other Intervention Names

Acetylsalicylic acid (ASA)

Eligibility Criteria

Inclusion Criteria

• Healthy adults aged 50-75 years who reside within the greater Twin Cities area
• Capable and willing to comply with the entire study protocol
• Able to give voluntary written informed consent.

Exclusion Criteria

• Use of any aspirin-containing products or other non-steroidal anti-inflammatory drugs (NSAIDs) (≥ 2 days per week on a regular basis)
• Known hypersensitivity to NSAIDs
• Any active cancer, history of gastrointestinal cancer, or chronic disease such as peptic ulcer, irritable bowel syndrome, inflammatory bowel disease, intestinal malabsorption syndrome or other gastrointestinal disorder
• History of any coagulation, bleeding, or blood disorders (e.g. Anemia)
• History of stroke/ Transient Ischemic Attack
• Acute heart disease or history of heart attack, atrial fibrillation, or angina
• Diagnosis of dementia
• Use of antibiotics, antiplatelets (e.g. clopidogrel), or anticoagulants (e.g. warfarin) within the last 3 months. A complete list of contraindicated medications will be provided (Appendix A)
• Regular use of laxatives (e.g. Ex-lax, Dulcolax, Miralax) that may affect the microbiome ≥2 days a week (Appendix B)
• Body mass index (BMI) greater than or equal to 40 or less than or equal to 17 kg/m2 at screening visit
• Unexplained change in weight (>4.5 kg) within the past 6 months
• Major changes in eating habits within the past 3 months

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Prizment, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

Epidemiology Clinical Research Center

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

2016NTLS049

Identifier Type: OTHER

Identifier Source: secondary_id

2016NTLS049

Identifier Type: -

Identifier Source: org_study_id