Study Investigating the Ability of Plant Exosomes to Deliver Curcumin to Normal and Colon Cancer Tissue

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colon Cancer	Dietary Supplement: curcumin; Dietary Supplement: Curcumin conjugated with plant exosomes; Other: No intervention	Phase 1

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	7 participants
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
Study Start Date :	January 2011
Estimated Primary Completion Date :	January 2020
Estimated Study Completion Date :	December 2020

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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; no treatment

Outcome Measures

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Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. safety and tolerability of curcumin alone as determined by adverse events [ Time Frame: 7 days after study enrollment ]
   Curcumin will be taken orally.
2. effects of curcumin on normal and cancerous colon cells by measuring the biomarkers using histochemical staining [ Time Frame: 7 days after patient enrollment ]
3. the immune system response to curcumin, measured by serum cytokine levels [ Time Frame: 7 days after patient enrollment in study ]
4. 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 ]
5. measurement of curcumin alone on metabolic characteristics of normal colon mucosa and colon tumors [ Time Frame: 7 days after patient enrollment ]
6. 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.
7. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202

Sponsors and Collaborators

James Graham Brown Cancer Center

University of Louisville

Investigators

Principal Investigator:	Donald M Miller, MD, Ph.D	James Graham Brown Cancer Center
Principal Investigator:	Kelli B Dunn, MD	James Graham Brown Cancer Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wu K, Xing F, Wu SY, Watabe K. Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside. Biochim Biophys Acta. 2017 Dec;1868(2):538-563. doi: 10.1016/j.bbcan.2017.10.001. Epub 2017 Oct 18. Review.

Responsible Party:	James Graham Brown Cancer Center
ClinicalTrials.gov Identifier:	NCT01294072 History of Changes
Other Study ID Numbers:	BCC-GI-10 Curcumin
First Posted:	February 11, 2011
Last Update Posted:	March 3, 2017
Last Verified:	March 2017

Keywords provided by James Graham Brown Cancer Center:

curcumin; plant exosomes; malignant colon tissue

Additional relevant MeSH terms:

Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Curcumin	Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action