The purpose of this study is to determine the effects of 2 drugs (sulindac and Difluoromethylornithine (DFMO)) either alone or in combination on biomarkers found in urine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
500 mg oral for 14 days, combined with sulindac for 15 days
150 mg oral for 15 days, combined with DFMO for 14 days
Measure intra-subject urine N1-monoacetylspermidine and dcSAM variability during the pre-drug phase
Measure initial variability in levels of urinary biomarkers prior to initiation of drug treatment. Three blood draws over the first 14 days will be used to assess baseline variability.
Time frame: Week 1-Week 2
Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
Measure urinary biomarker dcSAM after 14 days of single agent DFMO. Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 2 (Treatment sequence A).
Time frame: Week 4
Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is started week 2 (Treatment sequence B).
Time frame: Week 4
Determine dcSAM and N1-monoacetylspermidine content of urine after 14 days of 150 mg sulindac daily combined with DFMO at 500 mg/day
Time frame: Week 20
Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 10 (Treatment sequence B)
Time frame: Week 12
Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is stated week 10 (Treatment sequence A).
Time frame: Week 12
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Determine if 2 weeks is sufficient time for dcSAM levels and N1-monoacetylspermidine content of urine to recover after stopping DFMO and sulindac
Time frame: Week 22
Determine the length of time it takes for sulindac or DFMO to induce measurable changes in biomarker content of urine
Time frame: Week 3-Week 25
Explore the effect of dietary intake of polyamine measured using the Arizona Food Frequency Questionnaire
Quantitate dietary polyamine levels over the course of the study and evaluate the effects on biomarkers evaluated in the primary outcome measures.
Time frame: Week 1-25