Graft Versus Host Disease, Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm
Conditions
Brief summary
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.
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.
Interventions
PROCEDUREBiospecimen Collection
Undergo collection of blood samples
DRUGMicroencapsulated Sodium Butyrate
Given PO
DRUGMicroencapsulated Sodium Propionate
Given PO
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects' ability to take at least 75% of the specified dose on a weekly basis (feasibility) | During 2 week intervention period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | 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 | Adverse events will be categorized by type, frequency, severity, attribution, onset, and duration. Safety summaries will inform dosing decisions. |
| blood and stool - Propionate content | At baseline and up to 3 weeks | 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. |
| blood and stool - Butyrate content | At baseline and up to 3 weeks | 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. |
| Dosing adherence measures | During 2 week intervention period | assessed by compliance subject's ability to take at least 75% of the specified dose on a weekly basis |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKaramjeet S Sandhu
City of Hope Medical Center
Outcome results
None listed