- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01636128
Urinary Biomarker Study With Sulindac and Difluoromethylornithine
July 28, 2014 updated by: Patricia Thompson-Carino, Cancer Prevention Pharmaceuticals, Inc.
A Phase 2 Urinary Biomarker Study of Polyamine Inhibition With Sulindac and Difluoromethylornithine (DFMO)
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 Overview
Status
Withdrawn
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age 40-65 years
- Fluent in English
- PS 0 ECOG
- Must be able to discontinue the use of aspirin, aspirin containing products, and other non-steroidal anti-inflammatory agents for the duration of the study agent administration period
- Negative fecal occult blood test
- Hemoglobin > 10g/dl, WBC must be >4,000 mm3, platelets must be > 100,000/mm3
- Serum creatinine must be < 1.5 m/dl
- Serum bilirubin must be < 2.0 mg/dl, AST and ALT must be < 1.5x upper limit of normal range
- Female participants must be postmenopausal (at least 1 year since the last menstrual period), surgically sterilized, or willing to use an effective birth control method (e.g., hormonal contraceptive, oral contraceptives, intrauterine device, diaphragm with spermicide, or abstinence) for the duration of the study. Male subjects must use an effective method of birth control throughout the duration of the study and should not impregnate a female.
- Females of childbearing potential must have a negative serum pregnancy test prior to the start of study medication.
- Able to give signed, written informed consent
Exclusion Criteria:
- Requires corticosteroids or nonsteroidal anti-inflammatory agents
- Individuals who are immunosuppressed by virtue of medication or disease. This includes participants known to have AIDS, subjects taking oral steroids, and subjects on immunosuppressants/immunomodulators (cyclosporine, chemotherapeutic agents, or biologic therapy)
- Current use of phenytoin or sulfonamides
- Current or recent (within 3 months) use of coumadin or other systemic anticoagulants.
- Frequently, chronic or moderate/severe gastric complaints. Upper gastrointestinal problems requiring prescription or nonprescription medical remedies for symptoms of heartburn, dyspepsia, nausea, or abdominal pain > once per week on average
- History of peptic ulcer, occult or gross intestinal bleeding
- Known intercurrent illness, including but no limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, renal disease, liver disease, ongoing or active infection, psychiatric illness, or other situations that would limit compliance or interfere with the ability to comply with the study regimen.
- History of bleeding or clotting disorders
- Individuals with seizures or history of seizures
- History of abnormal wound healing or repair, or conditions that predisposes to the same including diabetes
- Unwilling or unable to limit alcohol consumption to 2-3 servings per week during the study period (12oz beer, 1 oz per alcoholic beverage, 6 oz per wine)
- Individuals enrolled in or who plan to enroll in a clinical intervention trial. There must be a 30 day period between completing a previous study and enrolling in this study.
- Pregnant or lactating women
- Prior DFMO exposure
- History of allergic reaction (e.g., urticaria, asthma, rhinitis) or gastric intolerance attributed to NSAIDs
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sulindac first (Treatment Sequence B)
Sulindac alone, washout, DFMO alone, then combination of sulindac and DFMO
|
500 mg oral for 14 days, combined with sulindac for 15 days
Other Names:
150 mg oral for 15 days, combined with DFMO for 14 days
|
Experimental: DFMO first (Treatment Sequence A)
DFMO alone, followed by washout, sulindac alone, then combination of DFMO and sulindac
|
500 mg oral for 14 days, combined with sulindac for 15 days
Other Names:
150 mg oral for 15 days, combined with DFMO for 14 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measure intra-subject urine N1-monoacetylspermidine and dcSAM variability during the pre-drug phase
Time Frame: Week 1-Week 2
|
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.
|
Week 1-Week 2
|
Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
Time Frame: Week 4
|
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).
|
Week 4
|
Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
Time Frame: Week 4
|
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).
|
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
|
Week 20
|
|
Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
Time Frame: Week 12
|
Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 10 (Treatment sequence B)
|
Week 12
|
Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
Time Frame: Week 12
|
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).
|
Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
|
Week 3-Week 25
|
|
Explore the effect of dietary intake of polyamine measured using the Arizona Food Frequency Questionnaire
Time Frame: Week 1-25
|
Quantitate dietary polyamine levels over the course of the study and evaluate the effects on biomarkers evaluated in the primary outcome measures.
|
Week 1-25
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2014
Primary Completion (Anticipated)
March 1, 2016
Study Completion (Anticipated)
April 1, 2016
Study Registration Dates
First Submitted
July 2, 2012
First Submitted That Met QC Criteria
July 9, 2012
First Posted (Estimate)
July 10, 2012
Study Record Updates
Last Update Posted (Estimate)
July 30, 2014
Last Update Submitted That Met QC Criteria
July 28, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Trypanocidal Agents
- Ornithine Decarboxylase Inhibitors
- Eflornithine
- Sulindac
Other Study ID Numbers
- UA-UB-101
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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