Testing the Bioavailability of Phytonutrients, Curcumin and Ursolic Acid

Study Overview
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Brief Summary
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The primary objective of this research is to investigate the bioavailability of curcumin (CURC) and ursolic acid (UA) in a phase I clinical trial in healthy men and obtain biological material for bioavailability analysis.

Detailed Description
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Once a subject is consented and assigned to a cohort, the subject may undergo a digital rectal exam (DRE) and rectal swab fecal collection and provide research blood (including CBC and CMP safety labs) and urine. Medical history data will be collected and reviewed. The PI and/or study staff will provide supplement administration and supplement diary education prior to the subject starting their dose of UA, CURC, or UA and CURC combination. Pharmacokinetic (PK) and pharmacodynamic (PD) assessments will be collected at pre-dose and 6 and 24 hours after the first dose. Urine will also be collected at pre dose and 24 hours post dose. The dosing period will be for a total of 2 weeks (± 3 days). On the last day of dosing, subjects will attend a research only visit at which the subject may undergo a digital rectal exam (DRE) and rectal swab fecal collection and provide research blood and urine. At this time, the subject's supplement diary will be reviewed and a safety/AE assessment will be completed. In addition, research CBC and CMP safety labs will be collected. If a subject initially enrolled in Cohort 1 or 2 decides to continue in Cohort 3, the subject will undergo a wash out period of at least 4 weeks and repeat all study procedures for Cohort 3.

Official Title
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Phase I Clinical Trial Testing the Bioavailability of Phytonutrients, Curcumin and Ursolic Acid

Conditions
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Bioavailability of Phytonutrients

Intervention / Treatment
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* Drug: Ursolic Acid
* Drug: Curcumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to give informed consent Be men age 18 or older Able to stop supplements Exclusion Criteria: Unable to give informed consent Age < 18 Woman Prisoners Diagnosed cancer Unable to swallow pills Unable to stop supplements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Cohort 1 and 2 will receive either UA or CURC and Cohort 3 will receive a combination of UA and CURC. Subjects initially enrolled in Cohorts 1 and 2 may have the option to continue in Cohort 3.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ursolic Acid<br>Administration of Ursolic Acid twice a day for 2 weeks | Drug: Ursolic Acid<br>* Ursolic Acid 150mg<br>|
| Experimental: Curcumin<br>Administration of Curcumin twice a day for 2 weeks | Drug: Curcumin<br>* Curcumin 600mg<br>|
| Experimental: Ursolic Acid and Curcumin<br>Administration of Ursolic Acid and Curcumin. If subjects from Cohort 1 or 2 wish to continue in the study, they will undergo a washout period of at least 4 weeks before participating in Cohort 3 | Drug: Ursolic Acid<br>* Ursolic Acid 150mg<br>Drug: Curcumin<br>* Curcumin 600mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, frequency, duration, and relation of toxicity events | Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC and UA, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. | Baseline to 2 weeks | 
| Peak serum concentration | Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed. | Baseline to 2 weeks | 
| Time to reach peak serum concentration | The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed. | Baseline to 2 weeks | 
| Half-life | The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed. | Baseline to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome Alpha Diversity | Number of bacteria collected from rectal culture sample will be assessed before and after each exposure | Baseline to 2 weeks | 
| Microbiome Beta Diversity | Proportions of bacteria collected from rectal culture sample will be assessed before and after each exposure | Baseline to 2 weeks | 
| Metabolite Panels | Metabolite panels will be placed into quartiles and compared to predicted function from the bioinformatics tool Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. | Baseline to 2 weeks |