Evaluating the Effects of Propionate and Butyrate Supplementation on the Intestinal Health of Healthy Volunteers

A Pilot Feasibility Study of Oral Administration of Microencapsulated Propionate and Butyrate in Healthy Volunteers

This clinical trial evaluates how propionate and butyrate supplementation alters intestinal health in healthy volunteers and whether it would be feasible to administer these supplements to patients undergoing allogeneic hematopoietic stem cell transplant in the future. Propionate and butyrate are short chain fatty acids naturally produced in the intestines during the fermentation of dietary fibers. Greater levels of propionate and butyrate may improve intestinal barrier function, and propionate specifically has been shown to modulate immunity, energy metabolism, and gut-brain communication. The protective effects of propionate and butyrate supplementation on intestinal health may be especially beneficial for patients undergoing donor stem cell transplant, as these patients can experience significant gastrointestinal injury during treatment. The results of this study may help researchers determine whether propionate and butyrate supplementation positively alters the gut microbiome and whether or not supplementation could be used in the future for patients undergoing a donor stem cell transplant.

Study Overview

• Status: Not yet recruiting
• Conditions: Malignant Solid Neoplasm; Graft Versus Host Disease; Hematopoietic and Lymphatic System Neoplasm
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Microencapsulated Sodium Butyrate; Drug: Microencapsulated Sodium Propionate

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the feasibility of repeated microencapsulated propionate and butyrate (mPB) administration as assessed by compliance; ability to consume at least 75% of the scheduled doses on a weekly basis.

SECONDARY OBJECTIVES:

I. To determine the safety of repeated mPB administration. II. To estimate blood and stool levels of propionate and butyrate metabolite content with repeated administration of mPB.

III. To identify a feasible target dose (TD) of repeated mPB administration in transplant patients as determined by dosing adherence and pharmacokinetic measures in blood and stool of healthy volunteers.

OUTLINE:

Participants receive microencapsulated sodium propionate orally (PO) four times daily (QID) for 1 week. Participants then receive microencapsulated sodium propionate PO QID and microencapsulated sodium butyrate PO QID for 1 week. Participants also undergo collection of blood samples throughout the study.

After completion of study intervention, participants are followed up for 1 week.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Contact: Karamjeet S. Sandhu; Phone Number: 626-218-2405; Email: ksandhu@coh.org
      • Principal Investigator: Karamjeet S. Sandhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative
• Age: ≥ 18 years and ≤ 75 years old
• Ability to read and understand and willingness to sign a written informed consent
• Ability to understand English to fill out required forms (e.g. Pill Diary and Symptom Diary)

• Participants are not taking butyrate or propionate as supplement(s)

  • Those who are already taking butyrate or propionate as supplement(s) are allowed only if they are willing to stop the supplement(s) ≥ 7 days prior to baseline samples and for the duration of this study

Exclusion Criteria:

• History of migraines and chronic gastrointestinal diseases, such as inflammatory bowel disease or Crohn's disease
• History of allergic reactions to compounds of similar chemical or biologic composition to study agent
• Females only: Pregnant, breastfeeding, or planning to get pregnant
• Antibiotic exposure within 2 weeks prior to day 1 of study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Supportive care (mPB); Participants receive microencapsulated sodium propionate PO QID for 1 week. Participants then receive microencapsulated sodium propionate PO QID and microencapsulated sodium butyrate PO QID for 1 week. Participants also undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Microencapsulated Sodium Butyrate; Given PO; Other Names: MSB; Microencapsulated Formulation-containing Sodium Butyrate; Drug: Microencapsulated Sodium Propionate; Given PO; Other Names: Microencapsulated Formulation-containing Sodium Propionate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects' ability to take at least 75% of the specified dose on a weekly basis (feasibility)	Evaluated by assessment of subject's ability to take at least 75% of the specified dose on a weekly basis. Vomiting within an hour after taking a dose will be considered a missed dose. Participants who do not meet this criterion will be considered as feasibility failure.	During 2 week intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Adverse events will be categorized by type, frequency, severity, attribution, onset, and duration. Safety summaries will inform dosing decisions.	From the first dose of microencapsulated sodium propionate to the first observation of toxicities or by day +7 after the last dose of microencapsulated propionate and butyrate
blood and stool - Propionate content	Longitudinal blood and stool concentrations of propionate will be analyzed relative to baseline using complementary modeling approaches. First, repeated measurements over time will be analyzed using linear mixed-effects models with subject-specific random effects to account for within-individual correlation and irregular sampling, allowing estimation of population-level temporal exposure patterns following dosing. Second, cumulative metabolite exposure from baseline will be summarized at the subject level using area-under-the-curve (AUC) metrics, calculated using the trapezoidal rule. These AUC measures provide an integrated summary of longitudinal exposure and will be used to characterize dose-exposure relationships and inter-individual variability. Exposure estimates derived from healthy volunteers will inform dose selection and optimization for subsequent studies in transplant patients.	At baseline and up to 3 weeks
blood and stool - Butyrate content	Longitudinal blood and stool concentrations of butyrate will be analyzed relative to baseline using complementary modeling approaches. First, repeated measurements over time will be analyzed using linear mixed-effects models with subject-specific random effects to account for within-individual correlation and irregular sampling, allowing estimation of population-level temporal exposure patterns following dosing. Second, cumulative metabolite exposure from baseline will be summarized at the subject level using area-under-the-curve (AUC) metrics, calculated using the trapezoidal rule. These AUC measures provide an integrated summary of longitudinal exposure and will be used to characterize dose-exposure relationships and inter-individual variability. Exposure estimates derived from healthy volunteers will inform dose selection and optimization for subsequent studies in transplant patients.	At baseline and up to 3 weeks
Dosing adherence measures	assessed by compliance subject's ability to take at least 75% of the specified dose on a weekly basis	During 2 week intervention period

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Karamjeet S Sandhu, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling
• Other Study ID Numbers: 25518 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-03337 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No