Chronic Kidney DiseasesNCT04204174
Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome
A study testing Tyrosine, brand name: myprotein in people with Chronic Kidney Diseases and Healthy, run by Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation at 1 site in Taiwan.
Trial summary
Patients with chronic kidney disease (CKD) display a substantial increase in cardiovascular disease (CVD). Moreover, the prognosis of CVD in CKD is extremely poor. Understanding the pathophysiology of CVD in CKD might help to develop treatment strategies to reduce its morbidity and mortality. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Diseases, Healthy
- What is being tested?
- Tyrosine, brand name: myprotein
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- 16 Dec 2019to 28 Feb 2020
- Phase
- Interventional
- 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- chronic kidney disease stages 3-5D patients OR
- healthy volunteers
Who cannot join
- subjects who has ever exposure to antibiotics or probiotics within the 3 months before entering the study
- patients with active gastrointestinal diseases or recent gastrointestinal discomfort (such as abdominal pain or diarrhea)
- patients with liver cirrhosis
- pregnant or breastfeeding women
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Tzu Chi Hospital
New Taipei City, 231
Ting-Yun Lin, MD, 8862-6628-9779 ext. 2350, water_h2o_6@hotmail.com
Szu-chun Hung, MD, 8862-6628-9779 ext. 2350, szuchun.hung@gmail.com
About this study
Patients with chronic kidney disease (CKD) display a substantial increase in cardiovascular disease (CVD). Moreover, the prognosis of CVD in CKD is extremely poor. Understanding the pathophysiology of CVD in CKD might help to develop treatment strategies to reduce its morbidity and mortality. Compelling evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD in CKD. The gut microbiota is markedly altered in CKD. Fermentation of protein and amino acids by certain gut microbiota results in the generation of different uremic toxins. p-cresyl sulfate (PCS) is among the most representative gut-derived uremic toxins implicated in the pathogenesis of CVD in CKD. However, there remained no clear cut-off value of fasting plasma PCS for unfavorable clinical outcomes.
Thus, we plan to establish an oral tyrosine challenge test (OTCT) integrated with dietary patterns, gut microbiome, and serum biochemistry to assess PCS synthesis capacity from host-diet-microbiota interactions.
Read the detailed description
Patients with chronic kidney disease (CKD) display a substantial increase in cardiovascular disease (CVD). Moreover, the prognosis of CVD in CKD is extremely poor. Understanding the pathophysiology of CVD in CKD might help to develop treatment strategies to reduce its morbidity and mortality. Traditional CV risk factors for the general population, such as diabetes mellitus, high blood pressure, and dyslipidemia, are more common in patients with CKD, but cannot entirely explain the increased CV risk. Compelling evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD in CKD. The gut microbiota is markedly altered in CKD. Fermentation of protein and amino acids by certain gut microbiota results in the generation of different uremic toxins. p-cresyl sulfate (PCS) is among the most representative gut-derived uremic toxins implicated in the pathogenesis of CVD in CKD (JAHA 6:e005022, 2017). However, there remained no clear cut-off value of fasting plasma PCS for unfavorable clinical outcomes (Clin J Am Soc Nephrol 4:1551-8, 2009). The benefit of adding an orally administered adsorbent (AST-120) to standard therapy in unselected patients with moderate to severe CKD is also not supported by data from a recent randomized controlled trial (J Am Soc Nephrol 26:1732-46, 2015).
It has been shown that uremic toxicity is related to the peak rather than the time-averaged urea concentration (Perit Dial Int 9:257-60, 1989). PCS is mainly produced from the metabolism of dietary tyrosine by gut bacteria. PCS concentration may fluctuate widely from time to time in response to meals. A postprandial plasma PCS might theoretically reflect the pathophysiological level of PCS. Thus, we plan to establish an oral tyrosine challenge test (OTCT) to simulate the postprandial plasma PCS among patients with CKD to identify "PCS producers" who are likely to be at high risk for CVD and are more likely to respond to adsorbent therapy. The OTCT survey is integrated with dietary patterns, gut microbiome, and serum biochemistry to assess PCS synthesis capacity from host-diet-microbiota interactions.
- Conditions
- Chronic Kidney Diseases, Healthy
- Being tested
- Tyrosine, brand name: myprotein
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tyrosine, brand name: myproteinDietary supplement
tyrosine at a dose of 100 mg/kg is then administered orally to the participants once
| Study group | Role | What they receive |
|---|---|---|
| Tyrosine loading | Experimental | Not described Receives: Dietary Supplement: Tyrosine, brand name: myprotein |
What is being measured
The primary outcome is the main question the study is designed to answer.
level of serum p-cresyl sulfate
serum p-cresyl sulfate level after oral tyrosine loading up to 48 hours
Measured: the area under curve of serum p-cresyl sulfate
Secondary outcomes (1)
level of serum phenyl sulfate
serum phenyl sulfate level after oral tyrosine loading up to 48 hours
Measured: the area under curve of serum phenyl sulfate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start16 Dec 2019
- Primary completion28 Feb 2020 (estimated)
- Study completion28 Feb 2020 (estimated)
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 Chronic Kidney DiseasesStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ting-Yun Lin, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
- Investigators
- Ting-Yun Lin, MD., Principal investigator, Taichung Tzu Chi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04204174
- Sponsor's protocol ID
- 08-X-108
- Status last verified
- Jan 2020
- First submitted
- 8 Dec 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We have decided yet.
Publications
Lin TY, Hung SC, Abe T. An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production. NPJ Metab Health Dis. 2026 Jun 2;4(1):20. doi: 10.1038/s44324-026-00114-4.
PubMed 42230971
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome
- ClinicalTrials.gov ID
- NCT04204174
- Acronym / sponsor ID
- 08-X-108
- Conditions
- Chronic Kidney Diseases, Healthy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationUniversity, hospital or other
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 28 Feb 2020 (estimated)
- First posted
- 18 Dec 2019 (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.
Patients with chronic kidney disease (CKD) display a substantial increase in cardiovascular disease (CVD). Moreover, the prognosis of CVD in CKD is extremely poor. Understanding the pathophysiology of CVD in CKD might help to develop treatment strategies to reduce its morbidity and mortality. Compelling evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD in CKD. The gut microbiota is markedly altered in CKD. Fermentation of protein and amino acids by certain gut microbiota results in the generation of different uremic toxins. p-cresyl sulfate (PCS) is among the most representative gut-derived uremic toxins implicated in the pathogenesis of CVD in CKD. However, there remained no clear cut-off value of fasting plasma PCS for unfavorable clinical outcomes.
Thus, we plan to establish an oral tyrosine challenge test (OTCT) integrated with dietary patterns, gut microbiome, and serum biochemistry to assess PCS synthesis capacity from host-diet-microbiota interactions.
Detailed description
Patients with chronic kidney disease (CKD) display a substantial increase in cardiovascular disease (CVD). Moreover, the prognosis of CVD in CKD is extremely poor. Understanding the pathophysiology of CVD in CKD might help to develop treatment strategies to reduce its morbidity and mortality. Traditional CV risk factors for the general population, such as diabetes mellitus, high blood pressure, and dyslipidemia, are more common in patients with CKD, but cannot entirely explain the increased CV risk. Compelling evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD in CKD. The gut microbiota is markedly altered in CKD. Fermentation of protein and amino acids by certain gut microbiota results in the generation of different uremic toxins. p-cresyl sulfate (PCS) is among the most representative gut-derived uremic toxins implicated in the pathogenesis of CVD in CKD (JAHA 6:e005022, 2017). However, there remained no clear cut-off value of fasting plasma PCS for unfavorable clinical outcomes (Clin J Am Soc Nephrol 4:1551-8, 2009). The benefit of adding an orally administered adsorbent (AST-120) to standard therapy in unselected patients with moderate to severe CKD is also not supported by data from a recent randomized controlled trial (J Am Soc Nephrol 26:1732-46, 2015).
It has been shown that uremic toxicity is related to the peak rather than the time-averaged urea concentration (Perit Dial Int 9:257-60, 1989). PCS is mainly produced from the metabolism of dietary tyrosine by gut bacteria. PCS concentration may fluctuate widely from time to time in response to meals. A postprandial plasma PCS might theoretically reflect the pathophysiological level of PCS. Thus, we plan to establish an oral tyrosine challenge test (OTCT) to simulate the postprandial plasma PCS among patients with CKD to identify "PCS producers" who are likely to be at high risk for CVD and are more likely to respond to adsorbent therapy. The OTCT survey is integrated with dietary patterns, gut microbiome, and serum biochemistry to assess PCS synthesis capacity from host-diet-microbiota interactions.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tyrosine loading | Experimental | Dietary Supplement: Tyrosine, brand name: myprotein |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- chronic kidney disease stages 3-5D patients OR
- healthy volunteers
Key exclusion criteria (4 listed)
- subjects who has ever exposure to antibiotics or probiotics within the 3 months before entering the study
- patients with active gastrointestinal diseases or recent gastrointestinal discomfort (such as abdominal pain or diarrhea)
- patients with liver cirrhosis
- pregnant or breastfeeding women
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 |
|---|---|---|
| Tyrosine, brand name: myproteintyrosine at a dose of 100 mg/kg is then administered orally to the participants once | Dietary supplement | Tyrosine loading |
Primary outcome
level of serum p-cresyl sulfate
Time frame: the area under curve of serum p-cresyl sulfate
serum p-cresyl sulfate level after oral tyrosine loading up to 48 hours
1 secondary outcome
level of serum phenyl sulfate
Time frame: the area under curve of serum phenyl sulfate
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Derived from this study: PubMed 42230971Lin TY, Hung SC, Abe T. An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production. NPJ Metab Health Dis. 2026 Jun 2;4(1):20. doi: 10.1038/s44324-026-00114-4.
- Individual participant dataSharing planned: Undecided. We have decided yet.
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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.
Ting-Yun Lin, MD. principal investigator
Taichung Tzu Chi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tyrosine, brand name: myprotein in people with Chronic Kidney Diseases and Healthy, run by Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation at 1 site in Taiwan.
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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 18 Jan 2020. 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 Taiwan. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ting-Yun Lin, MD. (+886-2-66289779 ext. 2350, water_h2o_6@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
level of serum p-cresyl sulfate (time frame: the area under curve of serum p-cresyl sulfate). 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 NCT04204174, 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 18 Jan 2020.