Studies of Sulfur Metabolism in Humans

Early Phase 1

Completed

• Conditions: Metabolic Side Effects of Drugs
• Interventions: Drug: SULT Allosteric Inhibition

• Registration Number: NCT03383133
• Lead Sponsor: Albert Einstein College of Medicine

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.

Study Timeline

• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2017-12-19
• Study First Posted: 2017-12-26
• Study Start: 2018-01-11
• Primary Completion: 2023-02-02
• Study Completion: 2023-02-02
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-25
• Last Update Posted: 2023-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SULT Allosteric Inhibition	SULT Allosteric Inhibition	A single, therapeutic dose of acetaminophen (1.0 g)) or dehydroepiandrosterone (75 mg) is taken orally (with 375 ml of water) either alone or simultaneously with a single, oral, therapeutic dose of mefenamic acid (0.75 g).

Primary Outcome Measures

Name	Time	Method
Acetaminophen and Dehydroepiandrosterone Conjugates	15min, 30min, 1hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr, 9hr, 10hr, 11hr, and 12hr following administration.	Proton NMR Signals will be used to quantitate conjugates of acetaminophen and dehydroepiandrosterone in urine.

Trial Locations

Locations (1)

Albert Einstein Collage of Medicine; 🇺🇸 Bronx, New York, United States