Trial record 2 of 99 for:    curcumin

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by James Graham Brown Cancer Center
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
James Graham Brown Cancer Center
ClinicalTrials.gov Identifier:
NCT01294072
First received: February 3, 2011
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Colon Cancer
Dietary Supplement: curcumin
Dietary Supplement: Curcumin conjugated with plant exosomes
Other: No intervention
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by James Graham Brown Cancer Center:

Primary Outcome Measures:
  • Concentration of curcumin in normal and cancerous tissue [ Time Frame: 7 days after start of curcumin ingestion ] [ Designated as safety issue: Yes ]
    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:
  • safety and tolerability of curcumin alone as determined by adverse events [ Time Frame: 7 days after study enrollment ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • the immune system response to curcumin, measured by serum cytokine levels [ Time Frame: 7 days after patient enrollment in study ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • measurement of curcumin alone on metabolic characteristics of normal colon mucosa and colon tumors [ Time Frame: 7 days after patient enrollment ] [ Designated as safety issue: No ]
  • safety and tolerability of curcumin with plant exosomes as determined by adverse events [ Time Frame: 7 days after study enrollment ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: January 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01294072

Contacts
Contact: Donald M Miller, MD, Ph.D 502-562-4790 donald.miller@louisville.edu
Contact: Nagendra Natarajan, MD 502-562-4790 nagendra.natarajan@louisville.edu

Locations
United States, Kentucky
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Principal Investigator: Donald M Miller, MD, Ph.D         
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

No publications provided

Responsible Party: James Graham Brown Cancer Center
ClinicalTrials.gov Identifier: NCT01294072     History of Changes
Other Study ID Numbers: BCC-GI-10 Curcumin
Study First Received: February 3, 2011
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by James Graham Brown Cancer Center:
curcumin
plant exosomes
malignant colon tissue

Additional relevant MeSH terms:
Curcumin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014