Study Investigating the Ability of Plant Exosomes to Deliver Curcumin to Normal and Colon Cancer Tissue
| Status: | Completed |
|---|---|
| Conditions: | Colorectal Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 20 - Any |
| Updated: | 4/2/2016 |
| Start Date: | January 2011 |
| End Date: | December 2015 |
| Contact: | Donald M Miller, MD, Ph.D |
| Email: | donald.miller@louisville.edu |
| Phone: | 502-562-4790 |
Phase I Clinical Trial Investigating the Ability of Plant Exosomes to Deliver Curcumin to Normal and Malignant Colon Tissue
This clinical trial will investigate the ability of plant exosomes to more effectively
deliver curcumin to normal colon tissue and colon tumors. Curcumin is the yellow pigment of
turmeric, a natural product with diverse biological activities. Exosomes are small
endosome-derived vesicles (50-100 nanometers [nm] in size). Previous clinical trials
conducted with oral curcumin have demonstrated only limited bioavailability even at very
high doses of 8-12 grams per day. This trial plans to address this problem of curcumin
delivery by using plant exosomes to deliver the drug to colon tumors and normal colon
tissue.
deliver curcumin to normal colon tissue and colon tumors. Curcumin is the yellow pigment of
turmeric, a natural product with diverse biological activities. Exosomes are small
endosome-derived vesicles (50-100 nanometers [nm] in size). Previous clinical trials
conducted with oral curcumin have demonstrated only limited bioavailability even at very
high doses of 8-12 grams per day. This trial plans to address this problem of curcumin
delivery by using plant exosomes to deliver the drug to colon tumors and normal colon
tissue.
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.
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.
Inclusion Criteria:
- Subjects must have definitive diagnosis of colon cancer.
- Surgical resection of the primary tumor must be an option for the newly diagnosed
cancer.
- No history of diabetes
- Subjects must be informed of the investigational nature of this study and sign and
give written informed consent in accordance with institutional and federal
guidelines.
- Absence of life-limiting medical conditions
- Ability to understand and willingness to sign a written informed consent document.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Karnofsky >
60%; see Appendix A).
- Subjects must have adequate bone marrow function. ANC > 1000/microliters (microL) and
Platelet count >100,000/microL
- Age >20 years
Exclusion Criteria:
- Known familial colon cancer syndrome
- Pregnancy
- Known Human Immunodeficiency Virus (HIV)
- Patients receiving immunosuppressive drugs
- Inflammatory bowel disease
- Active second malignancy in the last 5 years
- Patients receiving any other investigational agent(s)
- Patients who have received any prior chemotherapy or radiation therapy to the primary
colon cancer
- Intolerance to grapes, grapefruit, or curcumin
- History of diabetes mellitus
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