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NCT Number: NCT03182595

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

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.

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Key information

Conditions

Healthy Volunteers

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Hospital da Luz

Lisbon, 1500-650, Portugal

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy males and females, over 18 years of age,
  • Informed of the nature of the study and giving written informed consent,
  • Report no significant diseases during screening,
  • Have normal CBC, renal function and liver enzymology,
  • Have no contraindication for paracetamol,
  • Be on no regular medical treatment, except for contraceptives,
  • Be able to communicate effectively with study personnel.

Exclusion criteria

  • Hypersensitivity or idiosyncratic reaction to paracetamol,
  • Intake of any medication, except for contraceptives, within 14 days before start of the study,
  • Pregnancy or breastfeeding,
  • BMI <18 kg/m2,
  • Participation in a clinical study of any investigational product 1 month prior to visit 1 or during the study.

Treatment and study plan

Paracetamol

Drug

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.

Primary outcomes

  1. - Coefficient of variation of paracetamol sulfonation index (PSI), a ratio between the measured plasma concentrations of paracetamol sulfate (PS) and PS+ paracetamol glucoronide (PG) + paracetamol (P)

    Time frame: 9 months

Secondary outcomes

  1. Reproductibility, sensitivity and accuracy of the HPLC method (human samples will be used to validate the method);

    Time frame: 9 months

  2. Relationships between PSI and subject characteristics (gender, age, genotype, smoking status, caffeine consumption, alcohol consumption, oral contraceptive use);

    Time frame: 9 months

  3. Relationship between SULTA1 expression and predose and postdose metabolic profiles;

    Time frame: 9 months

  4. Association between SULT1A1 genotype and SULT1A1 expression (optional);

    Time frame: 9 months

  5. Association between PSI and SULT1A1 genotype (optional).

    Time frame: 9 months

Sponsors and collaborators

Lead sponsor

Hospital da Luz, Portugal

Other

Collaborators

  • Universidade Nova de Lisboa

Registry information

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jun 9, 2017
Registry last updated
Aug 25, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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