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Twelve patients found to be colonized with C. difficile will undergo twice a day potato starch supplementation.

Potato starch will be given twice a day for up to 14 days, discharge, or death, whichever occurs first.

Potato starch

Clostridium difficile causes \~453,000 infections and \~29,300 deaths per year in the US, making it the most common hospital acquired infection in the country. C. difficile is an anaerobic bacterium that has the capacity to inhabit the colon of humans and other mammals. Initially thought to be a commensal, it was later found to be associated with antibiotic induced enterocolitis. Since then, it has gradually become one of the most important healthcare associated pathogens. C. difficile infection (CDI) causes colitis, which is inflammation of the colonic mucosa with a spectrum of severity from mild to more protracted diarrhea, abdominal pain, fever, toxic megacolon, sepsis, and in some instances death. Mortality occurs despite the existence of three antibiotic options. CDI is also associated with higher hospital readmission rates, and associated healthcare costs in the US are estimated at 4.8 billion dollars annually. Due to the significance of C. difficile in healthcare, hospital level C. difficile rates are publically reported and closely scrutinized by the Centers for Medicare and Medicaid. Standard infection control bundles are proving to be insufficient for controlling the national C. difficile problem. Better understanding of the biological steps preceding clinical infection and reversal of the underlying gut dysbiosis will allow us to curtail our C. difficile epidemic. The present study aims to manipulate the gut microbiota to halt the biological progression of C. difficile.

CDI is a serious problem in hematology-oncology patients. The incidence of CDI in the hematology-oncology population is much higher than in other populations and hematology-oncology inpatient units frequently have the highest incidence of CDI cases within an institution. Additionally, hematology-oncology patients have high rates of C. difficile colonization upon hospitalization and more than 50% of patients detected with C. difficile colonization before bone marrow transplantation end up diagnosed with hospital associated CDI. This finding is not trivial as CDI treatment with oral vancomycin causes major and prolonged perturbations of their intestinal microbiota, which has been associated with higher mortality. In addition to the usual complications of CDI, a higher incidence of graft-versus-host-disease has been described in patients with CDI.

Aim 1/Objective 1. Establish the feasibility of oligosaccharide supplementation and twice a week stool collections among 12 C. difficile colonized hematology-oncology inpatients. It will be determined if at least 70% of the oligosaccharide dosages are taken by at least 8 (\>=66%) of the 12 enrolled patients. Additionally, the ability to collect at least 50% of the scheduled stool samples will be evaluated.

Aim 1 will provide important information about the ideal food/drink to mix the potato starch supplemented in this study. The knowledge gained in this pilot will be used to design a future phase II or III clinical trial.

Aim 2. Explore the impact of oligosaccharide supplementation on C. difficile loads and relative abundance of Firmicutes. All stool samples will undergo 16S ribosomal ribonucleic acid (rRNA) and bioinformatics at the MCW's Genomic and Precision Medicine Center and C. difficile quantitative polymerase chain reaction (qPCR) at the PI's research laboratory. Historical controls will be obtained from a group of over 450 hematology-oncology inpatients who underwent at least one C. difficile surveillance test and whose stool samples are currently being processed for 16S rRNA by the PI's team. Controls at a 3:1 ratio with cases will be matched based on underlying disease, unit of admission, antibiotic use, baseline C. difficile fecal loads, and baseline relative abundance of Firmicutes.

Objective 2a. Evaluate the impact of oligosaccharide supplementation on the change of C. difficile fecal loads when compared to historical controls.

Objective 2b. Explore the effect of oligosaccharide supplementation on the change in relative abundance of Firmicutes when compared to historical controls.

It is expected a reduction will occur in C. difficile fecal loads during oligosaccharide supplementation when compared to matched controls. Conversely, it is expected an increase in the relative abundance of Firmicutes (or some of its operational taxonomic units; OTUs) during oligosaccharide replacement will occur when compared to matched controls. The knowledge gained with Objectives 2a and 2b will be used to determine the sample size needed to design future phase II or phase III clinical trials.

Oligosaccharide for Cdiff(+) Heme-onc Patients

Oligosaccharide Supplementation Among Hematology-Oncology Clostridium Difficile Colonized Patients

Samples will be collected twice a week (4-5 times during supplementation) and one time at day 21 or discharge, whichever happens first.

Patients will be provided with a diary in which they will document compliance with oligosaccharide intake. It is anticipated ≥70% of intended doses to be fully administered by the patient.

It is expected ≥50% of stool samples to be correctly collected and processed.

Stool samples collected for diagnosis and any additional stool collections will be thawed in batches and one cc aliquot will be extracted refreezing the remaining sample at -80 degrees F. One cc aliquot will then be divided into 4 sub-samples of equal volume and with the same unique identifier. This identifier will be able to chronologically cluster samples by each unique patient. A sample will be used for C. difficile qPCR quantitative determination.

Sub-sample of stool from diagnosis, and additional stool collections will be used for 16S ribosomal ribonucleic acid gene sequencing to determine the microbiome community structure

Medical College of Wisconsin

Professor

Antineoplastic Agents

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Immune Checkpoint Inhibitors

Patients undergoing cancer treatment with dual immune checkpoint inhibitors (ICI) will receive potato-based dietary starch supplements.

Starting 5-7 days before treatment with dual-ICI, participant will consume 20g of potato starch (Bob's Red Mill®) once a day for 3 days, then increase to 20g twice a day, continuing throughout dual-ICI treatment (total duration approximately 13 weeks).

Leslie Fecher

This is a pilot study designed to assess the safety and feasibility of administering a dietary supplement to patients undergoing cancer treatment with a dual immune checkpoint inhibitors (ICIs) for solid cancer.

Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors

Pilot Study of Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors

Feasibility will be determined by calculating the number of patients who have taken 70% or more of scheduled dose of dietary intervention. Patients will be asked to record doses of starch taken and will be provided a table in which doses can be checked off.

Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency of known serious effects of ICIs will be compared to historical rates.

Adverse events will be assessed using the NCI CTCAE, version 5.0.

Graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Weekly stool samples will be compared to the baseline sample (prior to starting starch-based dietary supplement). Stool samples will be analyzed for microbial nucleic acids to characterize the components of the stool microbiome.

Weekly stool samples will be compared to the baseline sample (prior to starting starch-based dietary supplement). Key metabolic byproducts will be identified in stool specimens using liquid chromatography and mass spectrometry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oligosaccharide for Cdiff(+) Heme-onc Patients	NCT03778606	Clostridium Dif... Hematologic Dis...	Potato starch	18 Years -	Medical College of Wisconsin
Oligosaccharide for Cdiff(+) Heme-onc Patients	NCT03778606	Clostridium Dif... Hematologic Dis...	Potato starch	18 Years -	Medical College of Wisconsin
Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors	NCT04552418	Solid Tumor	Potato starch	18 Years -	University of Michigan Rogel Cancer Center
Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors	NCT04552418	Solid Tumor	Potato starch	18 Years -	University of Michigan Rogel Cancer Center

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