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

NCT ID: NCT01294072

Last Updated: 2023-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colon Cancer

Keywords

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curcumin plant exosomes malignant colon tissue

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

curcumin alone in capsule form (Arm 1) curcumin combined with plant exosomes (Arm 2) will not take curcumin or plant exosomes (Arm 3)
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Arm 1: Curcumin alone

Subjects take curcumin orally.

Group Type EXPERIMENTAL

curcumin

Intervention Type DIETARY_SUPPLEMENT

tablets-3.6 gram (gm) taken daily for 7 days - 15 subjects

Arm 2: Curcumin with plant exosomes

Subjects take curcumin conjugated with plant exosomes.

Group Type EXPERIMENTAL

Curcumin conjugated with plant exosomes

Intervention Type DIETARY_SUPPLEMENT

tablets-taken daily for 7 days - 15 subjects

Arm 3: no treatment

subjects will not take curcumin or plant exosomes

Group Type EXPERIMENTAL

No intervention

Intervention Type OTHER

no treatment

Interventions

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curcumin

tablets-3.6 gram (gm) taken daily for 7 days - 15 subjects

Intervention Type DIETARY_SUPPLEMENT

Curcumin conjugated with plant exosomes

tablets-taken daily for 7 days - 15 subjects

Intervention Type DIETARY_SUPPLEMENT

No intervention

no treatment

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Louisville

OTHER

Sponsor Role lead

Responsible Party

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Gerald W. Dryden, Jr.

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gerald W Dryden Jr, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville

Locations

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University of Louisville Hospital

Louisville, Kentucky, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Gerald W Dryden Jr, MD, Ph.D

Role: CONTACT

Phone: 502-852-6991

Email: [email protected]

References

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

Reference Type DERIVED
PMID: 29054476 (View on PubMed)

Other Identifiers

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BCC-GI-10 Curcumin

Identifier Type: -

Identifier Source: org_study_id