Brief Summary
The study test whether the NSAID allosteric site of human sulfotransferase 1A1 (SULT1A1) is operative in humans. The study will test the effects of mefenamic acid (MEF) on the sulfonation of acetaminophen (APAP, a SULT1A1 specific substrate) and dehydroepiandrosterone (DHEA, a SULT2A1 substrate). If the allosteric site is active in vivo, MEF is predicted to result in a decrease in sulfonation of APAP (MEF inhibits SULT with high affinity (Ki = 23 nM), and to have no effect on sulfonation of the DHEA (MEF has little or no effect on SULT2A1 activity).
Brief Title
Studies of Sulfur Metabolism in Humans
Detailed Description
No patient registries associated with this study.
A single, therapeutic dose of acetaminophen (APAP, 1.0 g)) or dehydroepiandrosterone (DHEA, 75 mg) is taken orally (with 375 ml of water) either alone or simultaneously with a single, oral, therapeutic dose of mefenamic acid (MEF, 0.75 g). In total, 5 experiments will be performed: 1, APAP alone; 2, DHEA alone; 3, MEF alone; 4, APAP + MEF; and 5, DHEA + MEF. Each experiment will be performed in duplicate. Compounds will be taken prior to eating breakfast. One hour later, the patient has a light breakfast (Cheerios and milk, and a cup of coffee) and eats normally thereafter. Urine samples are collected at 15', 30', 1 h, 2h, 3h, 4h, 5 h, 6h, 7h, 8h, 9h, 10h, 11h, and 12h intervals following dosing. The study subject will attempt to completely empty their bladder at each urine-collection time point. The samples are weighed. A 10 ml aliquot is taken from each time point and the aliquots are stored at -20 °C. Samples (0.5 ml) are then transferred to nuclear magnetic resonance (NMR) tubes and NMR spectra are taken to assess drug metabolites in urine. Proton NMR will be performed using the 600 MHz instrument in the Einstein facility.
A single, therapeutic dose of acetaminophen (APAP, 1.0 g)) or dehydroepiandrosterone (DHEA, 75 mg) is taken orally (with 375 ml of water) either alone or simultaneously with a single, oral, therapeutic dose of mefenamic acid (MEF, 0.75 g). In total, 5 experiments will be performed: 1, APAP alone; 2, DHEA alone; 3, MEF alone; 4, APAP + MEF; and 5, DHEA + MEF. Each experiment will be performed in duplicate. Compounds will be taken prior to eating breakfast. One hour later, the patient has a light breakfast (Cheerios and milk, and a cup of coffee) and eats normally thereafter. Urine samples are collected at 15', 30', 1 h, 2h, 3h, 4h, 5 h, 6h, 7h, 8h, 9h, 10h, 11h, and 12h intervals following dosing. The study subject will attempt to completely empty their bladder at each urine-collection time point. The samples are weighed. A 10 ml aliquot is taken from each time point and the aliquots are stored at -20 °C. Samples (0.5 ml) are then transferred to nuclear magnetic resonance (NMR) tubes and NMR spectra are taken to assess drug metabolites in urine. Proton NMR will be performed using the 600 MHz instrument in the Einstein facility.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metabolic Side Effects of Drugs
Eligibility Criteria
Inclusion criteria:
* Gender - one male
* Age - 61 y.o.
* Healthy
* Agreed to sign the consent form
Exclusion criteria:
● None
* Gender - one male
* Age - 61 y.o.
* Healthy
* Agreed to sign the consent form
Exclusion criteria:
● None
Inclusion Criteria
Inclusion criteria:
* Gender - one male
* Age - 61 y.o.
* Healthy
* Agreed to sign the consent form
* Gender - one male
* Age - 61 y.o.
* Healthy
* Agreed to sign the consent form
Gender
Male
Gender Based
false
Keywords
sulfotransferase
metabolism
acetaminophen
dehydroepiandrosterone
mefenamic acid
allostery
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
61 Years
Minimum Age
61 Years
NCT Id
NCT03383133
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2017-8685
Overall Status
Completed
Phases
Early Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Allosteric Regulation of Cytosolic Sulfotransferases in Humans
Primary Outcomes
Outcome Description
Proton NMR Signals will be used to quantitate conjugates of acetaminophen and dehydroepiandrosterone in urine.
Outcome Measure
Acetaminophen and Dehydroepiandrosterone Conjugates
Outcome Time Frame
15min, 30min, 1hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr, 9hr, 10hr, 11hr, and 12hr following administration.
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
61
Minimum Age Number (converted to Years and rounded down)
61
Investigators
Investigator Type
Principal Investigator
Investigator Name
Thomas Leyh
Investigator Email
tom.leyh@einsteinmed.org
Investigator Phone