Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome

Healthy Clinical Trial

Official title:

Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04204174
• Other study ID #: 08-X-108
• Status: Recruiting
• Phase: N/A
• Start date: December 16, 2019
• Est. completion date: February 28, 2020

Study information

• Verified date: January 2020
• Source: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
• Contact: Ting-Yun Lin, MD.
• Phone: +886-2-66289779
• Email: water_h2o_6[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 28, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• chronic kidney disease stages 3-5D patients OR

• healthy volunteers

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Healthy
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Tyrosine, brand name: myprotein
tyrosine at a dose of 100 mg/kg is then administered orally to the participants once

Locations

Country	Name	City	State
Taiwan	Taipei Tzu Chi Hospital	New Taipei City

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	level of serum p-cresyl sulfate	serum p-cresyl sulfate level after oral tyrosine loading up to 48 hours	the area under curve of serum p-cresyl sulfate
Secondary	level of serum phenyl sulfate	serum phenyl sulfate level after oral tyrosine loading up to 48 hours	the area under curve of serum phenyl sulfate