Clinical Trial: Phase II A Trial of Curcumin Among Patients With Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase IIA Trial of Curcumin Among Patients With Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)

Brief Summary: Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. Curcumin is a compound found in plants that may prevent colon cancer from forming. This phase II trial is studying how well curcumin works in preventing colon cancer in smokers with aberrant crypt foci.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose.

SECONDARY OBJECTIVS:

I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose.

II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose.

III. To quantify corresponding enzyme changes in the cyclooxygenases (COX-1, COX-2,) and lipoxygenase (5-LOX) protein abundance. Semi-quantitative changes in these proteins will be measured by western blotting and correlated with changes in prostaglandins and leukotrienes respectively.

IV. Document changes in total ACF number. V. Determine proliferation by Ki-67 IHC in rectal mucosa pre and post therapy and correlate with changes in ACF number and size.

VI. Determine curcumin concentration in rectal mucosa after 30 days therapy and correlate with PGE2 and 5-HETE changes described above.

VII. Measure glutathione peroxidase (GPx) activity within the colon pre and post therapy as an indirect marker of reduced oxidative stress within the colonic epithelium.

VIII. Ensure safety of all participants during course of study investigation. IX. Determine the curcumin concentration in plasma before and after treatment.

  • Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) [ Time Frame: Baseline ]
    Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue
  • Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF) [ Time Frame: At 30 day ]
    Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue


    • Original Primary Outcome:

    Current Secondary Outcome:

    • Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) [ Time Frame: Baseline ]
      Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue
    • Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF) [ Time Frame: At 30 Day ]
      Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue
    • Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa [ Time Frame: Baseline ]
      Baseline prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue
    • Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa [ Time Frame: At 30 day ]
      Post-treatment prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue
    • Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa [ Time Frame: Baseline ]
      Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue
    • Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa [ Time Frame: At 30 day ]
      Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue
    • Change in Cyclooxygenases (COX-1, COX-2), and Lipoxygenase (5-LOX) Protein Abundance [ Time Frame: Baseline to 30 days ]
      The protein levels for each enzyme will be expressed as an absolute change from baseline and graphed against % change of its enzyme product in the same individual. The degree of correlation between these parameters will be assessed by either Pearson's correlation coefficient or Spearman's rank order correlation coefficient.
    • Changes in Total Aberrant Crypt Foci (ACF) Number [ Time Frame: Baseline to 30 days ]
      Changes in total aberrant crypt foci (ACF) number = Number of ACF at pre-treatment - Number of ACF at post-treatment
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third [ Time Frame: Baseline ]
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third [ Time Frame: At 30 day ]
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third [ Time Frame: Baseline ]
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third [ Time Frame: At 30 day ]
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third [ Time Frame: Baseline ]
    • Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third [ Time Frame: At 30 day ]
    • Baseline Curcumin Concentration in Rectal Mucosa [ Time Frame: Baseline ]
      If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
    • Post-treatment Curcumin Concentration in Rectal Mucosa [ Time Frame: At 30 day ]
      If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.
    • Baseline Curcumin Plasma Concentrations [ Time Frame: Baseline ]
      Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.
    • Post-treatment Curcumin Plasma Concentrations [ Time Frame: At 30 day ]
      Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.