Healthy VolunteersPhase 1NCT03182595
Variability of Sulfotransferase 1A1 Activity in Humans: an Approach to Improve Predictive Drug Response - Part I: Analysis of Intraindividual Variation in Healthy Adults
A Phase 1 study testing Paracetamol in people with Healthy Volunteers, run by Hospital da Luz, Portugal at 1 site in Portugal.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Paracetamol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 sitePortugal
- Study dates
- 17 Mar 2017to 31 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Paracetamol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| open---label | Experimental | An open---label, single centre, nonrandomized clinical study in healthy volunteers, with intervention over a 13---week period. Receives: Drug: Paracetamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
- 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)
Measured: 9 months
Secondary outcomes (5)
Reproductibility, sensitivity and accuracy of the HPLC method (human samples will be used to validate the method);
Measured: 9 months
Relationships between PSI and subject characteristics (gender, age, genotype, smoking status, caffeine consumption, alcohol consumption, oral contraceptive use);
Measured: 9 months
Relationship between SULTA1 expression and predose and postdose metabolic profiles;
Measured: 9 months
Association between SULT1A1 genotype and SULT1A1 expression (optional);
Measured: 9 months
Association between PSI and SULT1A1 genotype (optional).
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start17 Mar 2017
- Primary completion31 Jan 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital da Luz, Portugal
- Sponsor type
- University, hospital or other
- Collaborators
- Universidade Nova de Lisboa
- Responsible party
- Sponsor
- Investigators
- Natália Marto, MD, Principal investigator, Hospital da Luz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03182595
- Sponsor's protocol ID
- HLUZ_001_2016
- Status last verified
- Aug 2021
- First submitted
- 25 May 2017
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marto N, Morello J, Antunes AMM, Azeredo S, Monteiro EC, Pereira SA. A simple method to measure sulfonation in man using paracetamol as probe drug. Sci Rep. 2021 Apr 27;11(1):9036. doi: 10.1038/s41598-021-88393-3.
PubMed 33907224
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Variability of Sulfotransferase 1A1 Activity in Humans: an Approach to Improve Predictive Drug Response - Part I: Analysis of Intraindividual Variation in Healthy Adults
- ClinicalTrials.gov ID
- NCT03182595
- Acronym / sponsor ID
- HLUZ_001_2016
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Hospital da Luz, PortugalUniversity, hospital or other
- Collaborators
- Universidade Nova de Lisboa
- Study start
- 17 Mar 2017 (actual)
- Primary completion
- 31 Jan 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 9 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| open---label | Experimental | Drug: ParacetamolAn open---label, single centre, nonrandomized clinical study in healthy volunteers, with intervention over a 13---week period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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,
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParacetamolVolunteers 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. | Drug | open---label |
Primary outcome
- 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
5 secondary outcomes
Reproductibility, sensitivity and accuracy of the HPLC method (human samples will be used to validate the method);
Time frame: 9 months
Relationships between PSI and subject characteristics (gender, age, genotype, smoking status, caffeine consumption, alcohol consumption, oral contraceptive use);
Time frame: 9 months
Relationship between SULTA1 expression and predose and postdose metabolic profiles;
Time frame: 9 months
Association between SULT1A1 genotype and SULT1A1 expression (optional);
Time frame: 9 months
Association between PSI and SULT1A1 genotype (optional).
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Derived from this study: PubMed 33907224Marto N, Morello J, Antunes AMM, Azeredo S, Monteiro EC, Pereira SA. A simple method to measure sulfonation in man using paracetamol as probe drug. Sci Rep. 2021 Apr 27;11(1):9036. doi: 10.1038/s41598-021-88393-3.
- Individual participant dataSharing planned: No
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Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natália Marto, MD principal investigator
Hospital da Luz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Paracetamol in people with Healthy Volunteers, run by Hospital da Luz, Portugal at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03182595, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.