Study Investigating the Ability of Plant Exosomes to Deliver Curcumin to Normal and Colon Cancer Tissue
|Colon Cancer||Dietary Supplement: curcumin Dietary Supplement: Curcumin conjugated with plant exosomes Other: No intervention||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Clinical Trial Investigating the Ability of Plant Exosomes to Deliver Curcumin to Normal and Malignant Colon Tissue|
- Concentration of curcumin in normal and cancerous tissue [ Time Frame: 7 days after start of curcumin ingestion ]Concentration of curcumin delivered with curcumin alone or curcumin conjugated with plant exosomes to normal and cancerous colon cells will be compared. This exploratory trial is designed to estimate the effect of a fixed concentration of curcumin when delivered by plant exosomes compared to oral tablets of curcumin alone.
- safety and tolerability of curcumin alone as determined by adverse events [ Time Frame: 7 days after study enrollment ]Curcumin will be taken orally.
- effects of curcumin on normal and cancerous colon cells by measuring the biomarkers using histochemical staining [ Time Frame: 7 days after patient enrollment ]
- the immune system response to curcumin, measured by serum cytokine levels [ Time Frame: 7 days after patient enrollment in study ]
- immune response in ex vivo cell cultures of colon cancer cells treated with curcumin and Exo-cur, to be evaluated by using histochemical staining [ Time Frame: 7 days after patient enrollment in study ]
- measurement of curcumin alone on metabolic characteristics of normal colon mucosa and colon tumors [ Time Frame: 7 days after patient enrollment ]
- safety and tolerability of curcumin with plant exosomes as determined by adverse events [ Time Frame: 7 days after study enrollment ]Curcumin and plant exosomes will be taken orally.
- measurement of curcumin mixed with plant exosomes on metabolic characteristics of normal colon mucosa and colon tumors [ Time Frame: 7 days after patient enrollment on study ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||January 2020 (Final data collection date for primary outcome measure)|
Experimental: Arm 1: Curcumin alone
Subjects take curcumin orally.
Dietary Supplement: curcumin
tablets-3.6 gram (gm) taken daily for 7 days - 15 subjects
Experimental: Arm 2: Curcumin with plant exosomes
Subjects take curcumin conjugated with plant exosomes.
Dietary Supplement: Curcumin conjugated with plant exosomes
tablets-taken daily for 7 days - 15 subjects
|Experimental: Arm 3: no treatment||
Other: No intervention
Curcumin is a constituent of the spice turmeric, which is one of the primary ingredients of curry powder. Curcumin has been shown to interfere with colon carcinogenesis in a variety of chemical and genetic rodent models. It has also been shown to have a strong inhibitory effect on the growth of colon cancer cell lines. There is considerable evidence that the effects of curcumin are mediated by changes in signal transduction. There is an extensive body of work showing effects on several signaling pathways, including the beta-catenin and NF-κB pathways. Although curcumin has been viewed as an ideal chemopreventative agent in colon cancer for many years, its application has been impeded by important issues with drug delivery and bioavailability in the reported clinical trials of this compound.
Work from the James Graham Brown Cancer Center published recently suggests that using exosomes as a delivery vehicle leads to overcoming all the major obstacles of using curcumin as an anti-inflammatory agent, including increased stability, solubility, and bioavailability of curcumin. The work was further extended to define the resource that can supply a large quantity of exosomes with a maximum binding capacity of curcumin. Emerging data indicate that exosomes derived from many fruits release exosome-like particles, strongly bind to many hydrophobic drugs including curcumin, and are taken up by the intestine cells as well as the immune cells in the intestine. These results suggest that these fruit-derived exosomes are potentially used as a delivery vehicle to treatment of intestinal diseases. Moreover, both fruit exosomes and curcumin should not generate any side-effects since they are consumed by humans daily.
In this clinical trial, the effect of exosomally delivered curcumin on the immune modulation, cellular metabolism, and phospholipid profile of normal and malignant colon cells in subjects who are undergoing surgery for newly diagnosed colon cancer will be characterized. In selected subjects, the effect of exosomally delivered curcumin on the production of cytokines, the changes of immune cells, and glucose metabolism by administration of 13C-glucose prior to surgical resection will also be characterized.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01294072
|United States, Kentucky|
|James Graham Brown Cancer Center|
|Louisville, Kentucky, United States, 40202|
|Principal Investigator:||Donald M Miller, MD, Ph.D||James Graham Brown Cancer Center|
|Principal Investigator:||Kelli B Dunn, MD||James Graham Brown Cancer Center|