NCT03182595

Variability of Sulfotransferase 1A1 Activity in Humans: an Approach to Improve Predictive Drug Response - Part I: Analysis of Intraindividual Variation in Healthy Adults

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Hospital da Luz, Portugal · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

An open-label, single centre, nonrandomized clinical study in healthy volunteers, with intervention over a 13---week period. After written informed consent, subjects will undergo screening evaluations (Visit 1). One week after visit 1, subjects who meet the selection criteria will enter a run---in period of 8 weeks where participants will receive paracetamol 1g tablet and collect a blood sample at monthly intervals (visits 2, 3 and 4). A final visit for safety assessment will take place at week 13 (visit 5). Blood samples will be used to quantify P, PG e PS.

Detailed description

To be able to predict efficacy and adverse reactions involving compounds metabolized by sulfonation, the investigators need more information on SULTs. Studies of in vivo sulfonation in humans are lacking, although they are of key importance in assessing the functional consequences of individual variation. In our current study, the investigators will start by developing an HPLC method of quantifying SULT1A1 activity using paracetamol as probe substrate and studying intraindividual variation in healthy adults. Advantages of using paracetamol as a probe substrate for in vivo phenotyping of SULT1A1 include: wide safety margin for in vivo use, easy and ready administration of the drug, significant metabolism by the enzyme of interest, short half---life, linear pharmacokinetics over a wide concentration range and a limited number of metabolites, quantifiable in plasma.15,24 In a subsequent study, the investigators plan to study interindividual variation in a larger sample, including subjects with chronic disease and on medication.The investigators expect to provide a valuable new tool to explore the clinical significance of variation of SULT1A1 activity, the most important SULT on drug metabolism.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	Paracetamol	Volunteers will be screened at visit 1, and if they meet the inclusion/exclusion criteria they will receive the intervention at visit 2. At visit 2, complying subjects will receive a tablet containing 1 gram of paracetamol and have a blood sample collected 2 hours after administration; these procedures will be repeated on 2 more occasions (visits 3 and 4). The subjects will come for 5 visits during the study. Visit 1 and 2 must occur within 7 days of each other, visits 2, 3 and 4 will be four weeks (± 3 days) apart and visit 5 scheduled four weeks (± 3 days) after visit 4.

Timeline

• Start date: 2017-03-17
• Primary completion: 2018-01-31
• Completion: 2018-12-31
• First posted: 2017-06-09
• Last updated: 2021-08-25

Locations

1 site across 1 country: Portugal