Probiotics for the Prevention of Immunotherapy Induced Colitis in Patients Receiving Immunotherapy

January 19, 2026 updated by: Mayo Clinic

Probiotics Preventing Immune Checkpoint Inhibitor-Induced Colitis

The clinical trial tests the use of over-the-counter probiotics VSL#3® 450B in patients receiving immunotherapy. Immunotherapy with monoclonal antibodies, helps the body's immune system attack tumor cells, and interferes with the ability of tumor cells to grow and spread. Immunotherapy can also cause an unfortunate side effect of inflammation of the colon and diarrhea, also known as immune checkpoint inhibitor induced colitis. Immune checkpoint inhibitor induced colitis can occur in up to 45% of patients receiving immunotherapy. Taking probiotics VSL#3® 450B may reduce the chances of developing immune checkpoint inhibitor induced colitis in patients receiving immunotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) in patients with solid malignancies receiving over-the-counter multi-strain probiotic blend and ICIs in both cohorts: (1) anti-Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) +/- anti-programmed cell death-1 (PD-1)/programmed cell death-1 ligand 1 (PD-L1), and (2) anti-PD-1/PD-L1 +/- chemo.

SECONDARY OBJECTIVES:

I. To evaluate the safety of multi-strain probiotic blend in cancer patients receiving ICIs.

II. To evaluate the clinical outcomes related to IIC, including the incidence of IIC, hospitalization, treatment delays, and administration of immunosuppressants.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in gut microbiome with ICIs and multi-strain probiotic blend.

II. To evaluate changes in immune response with ICIs and multi-strain probiotic blend.

OUTLINE:

Patients receive VSL#3® 450B (live freeze-dried lactic acid bacteria probiotic) orally (PO) once daily (QD) at least 3 days prior or 1-2 weeks prior to starting standard care ICIs or receiving the next cycle of ICIs and then continue for 12 weeks. Patients also undergo stool and blood sample collections on study.

After completion of study treatment, patients are followed up at 30 days and 1 year.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Histologically confirmed solid malignancy

  • Will be starting on ICIs or have started ≤ 2 cycles of ICIs

    • For cohort 1: Ipilimumab with or without anti-PD-1/PD-L1 including but not limited to pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, or durvalumab
    • For cohort 2: Anti-PD-1/PD-L1 described above with or without chemotherapy
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine ≤ 2 x upper limit of normal (ULN)
  • Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate transaminase (AST)] ≤ 2 x ULN
  • Albumin ≥ 3 g/dL
  • Willing and able to provide research stool and blood samples
  • Negative serum pregnancy test done ≤ 7 days prior to enrollment, for women of childbearing potential only
  • Capable of providing valid informed consent
  • Willing to return to enrolling institution for all study visits (blood draws, etc)

Exclusion Criteria:

  • Requires prolonged systemic antibiotic therapy for other condition and recent systemic antibiotic within the past 2 weeks
  • Fecal microbiota transplant (FMT) within the past 6 months
  • FMT with an associated serious adverse event related to the FMT product or procedure
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of over-the-counter probiotics
  • Immunocompromised patients including patients known to be HIV positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted
  • History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis
  • History of chronic diarrhea
  • History of celiac disease
  • Currently has a colostomy
  • Intraabdominal surgery related to gastrointestinal tract within the last 60 days
  • Evidence of active, severe colitis
  • History of short gut syndrome or motility disorders
  • Requires the regular use of medications to manage bowel hypermotility
  • Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (VSL#3® 450B)
Patients receive VSL#3® 450B (live freeze-dried lactic acid bacteria probiotic) PO QD at least 3 days prior or 1-2 weeks prior to starting standard care or receiving the next cycle of ICIs and then continue for 12 weeks. Patients also undergo stool and blood sample collections on study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo stool and blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Dietary supplement: Live Freeze-Dried Lactic Acid Bacteria Probiotic
Given PO
Other Names:
  • VSL#3
  • VSL3

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) with VSL#3 and ICIs
Time Frame: Up to 14 weeks
Will be evaluated in patients with solid malignancies in 2 cohorts, including 1) anti-CTLA4 ± anti-PD-1/PD-L1, 2) anti-PD-1/PD-L1 ± chemotherapy respectively. Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Will be estimated by the number of patients who had IIC divided by the total number of evaluable patients. Two-sided 90% exact confidence intervals for the true incidence rate will be calculated according to the approach of Clopper and Pearson.
Up to 14 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 30 days post treatment
Will be evaluated by the safety profile of multi-strain probiotic blend in cancer patients receiving ICIs. Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize toxicity.
Up to 30 days post treatment
Incidence of hospitalization related to IIC
Time Frame: Up to 14 weeks
Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.
Up to 14 weeks
Incidence of treatment delays related to IIC
Time Frame: Up to 14 weeks
Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.
Up to 14 weeks
Incidence of administration of immunosuppressants related to IIC
Time Frame: Up to 14 weeks
Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.
Up to 14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Saranya Chumsri, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 31, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 12, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 21, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MC210304 (Other Identifier: Mayo Clinic in Florida)
  • NCI-2024-05551 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 21-012363 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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