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

NCT ID: NCT04204174

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-16
• Study Completion Date: 2020-02-28

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Tyrosine loading

Group Type: EXPERIMENTAL

Tyrosine, brand name: myprotein

Intervention Type: DIETARY_SUPPLEMENT

tyrosine at a dose of 100 mg/kg is then administered orally to the participants once

Interventions

Tyrosine, brand name: myprotein

tyrosine at a dose of 100 mg/kg is then administered orally to the participants once

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

OTHER

Sponsor Role: lead

Responsible Party

Ting-Yun Lin

Nephrologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ting-Yun Lin, MD.

Role: PRINCIPAL_INVESTIGATOR

Taichung Tzu Chi Hospital

Locations

Taipei Tzu Chi Hospital

New Taipei City, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ting-Yun Lin, MD.

Role: CONTACT

water_h2o_6@hotmail.com

+886-2-66289779 ext. 2350

Facility Contacts

Ting-Yun Lin, MD

Role: primary

water_h2o_6@hotmail.com

8862-6628-9779 ext. 2350

Szu-chun Hung, MD

Role: backup

szuchun.hung@gmail.com

8862-6628-9779 ext. 2350

Other Identifiers

08-X-108

Identifier Type: -

Identifier Source: org_study_id