Clinical trial NCT03383133: Studies of Sulfur Metabolism in Humans
Official title: Allosteric Regulation of Cytosolic Sulfotransferases in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Metabolic Side Effects of Drugs
Keywords: sulfotransferase
metabolism
acetaminophen
dehydroepiandrosterone
mefenamic acid
allostery
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
First posted: 2017-12-26
Enrollment: 1
Sex: MALE
Minimum age (years): 61
Maximum age (years): 61
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study will involve only a single individual.
Primary purpose: BASIC_SCIENCE

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).

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.

Eligibility criteria: Inclusion criteria:

* Gender - one male
* Age - 61 y.o.
* Healthy
* Agreed to sign the consent form

Exclusion criteria:

● None

Primary outcomes:
measure: Acetaminophen and Dehydroepiandrosterone Conjugates
timeFrame: 15min, 30min, 1hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr, 9hr, 10hr, 11hr, and 12hr following administration.
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein Collage of Medicine
state: New York
Study officials:
affiliation: The Albert Einstein College of Medicine
name: Thomas S Leyh, Ph. D.
role: PRINCIPAL_INVESTIGATOR
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