NCT03383133

Studies of Sulfur Metabolism in Humans

Allosteric Regulation of Cytosolic Sulfotransferases in Humans

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Albert Einstein College of Medicine · Academic / Other
• Sex: Male
• Age: 61 Years – 61 Years
• Healthy volunteers: Not accepted

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).

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.

Conditions

• Metabolic Side Effects of Drugs

Interventions

Type	Name	Description
DRUG	SULT Allosteric Inhibition	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. Each experiment is performed in duplicate. Compounds are taken prior to eating breakfast. One hour later, the patient has a light breakfast 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 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 NMR tubes spectra are taken to assess drug metabolites in urine.

Timeline

• Start date: 2018-01-11
• Primary completion: 2023-02-02
• Completion: 2023-02-02
• First posted: 2017-12-26
• Last updated: 2023-10-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study