Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test

Healthy Clinical Trial

Official title:

Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04117191
• Other study ID #: 08-P-055
• Status: Completed
• Phase: N/A
• Start date: October 1, 2019
• Est. completion date: November 30, 2019

Study information

• Verified date: December 2019
• Source: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cardiovascular disease (CVD) is prevalent in patients with chronic kidney disease (CKD) and is associated with extremely poor prognosis. Traditional risk factors for the general population, such as diabetes mellitus, high blood pressure, and dyslipidemia, are more common in patients with CKD but cannot fully explain the increased risk of this population. New evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD. The gut microbiota is markedly altered in CKD, with overgrowth of bacteria that produce uremic toxins. Indoxyl sulfate (IS) is among the most representative gut‐derived uremic toxins and has been most frequently implicated as a contributor to the pathogenesis of CVD in CKD. IS is converted from indole, a gut bacteria metabolite of dietary tryptophan, by two hepatic enzymes, CYP2E1 and SULT1A1. The majority of studies have assessed IS toxicity in cultured cells and animal models. However, human data have been conflicting and the benefit of using orally administered adsorbents to reduce IS levels in unselected CKD patients was not supported by results from the recent randomized controlled trials. IS levels may fluctuate widely from time to time with dietary intakes. The investigators hypothesize that a postprandial IS concentration may more reflect its toxicity than a single time point (fasting or predialysis IS) concentration measured in clinical studies. Therefore, the investigators plan to establish an oral tryptophan challenge test (OTCT) by using an oral loading of 2 gm tryptophan to simulate the postprandial increase of plasma IS. The investigators will recruit 60 healthy volunteers to undergo OTCT. A pharmacokinetic study of IS after the OTCT will be performed in 20 of them to verify and simplify the design of OTCT protocol. The results of OTCT will be integrated with whole metagenome analysis of fecal microbiota and genetic polymorphism analysis of CYP2E1 and SULT1A1 to explore the mechanisms of IS production. In addition to the known genes in microbe produces indoles, other supporting bacteria or genes will be examined by using metagenomic shotgun sequencing data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 30, 2019
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• (1) age older than 20 years

• (2) no exposure to antibiotics or probiotics within the 3 months before entering the study.

Exclusion Criteria:

• (1) recent gastrointestinal discomfort (such as nausea, vomiting, abdominal pain, constipation, or diarrhea) or

• (2) a history of chronic diseases including diabetes mellites, hypertension, CVD, CKD, liver disease, malignancy, and autoimmune disease.

• (3) pregnancy or breast feeding

• (4) currently use of antipsychotics, Hypnotics, Demerol, Dextromethorphan, tramadol, pentazocine

Related Conditions & MeSH terms

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

Intervention

Dietary Supplement:
• Doctor's Best L-Tryptophan
2g tryptophan loading 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	Indoxyl sulfate	serum and urine indoxyl sulfate concentration measurement	the area under curve of serum and urine indoxyl sulfate within 72 hours
Secondary	Indole-3-acetic acid	serum and urine Indole-3-acetic acid concentration measurement	the area under curve of serum and urine Indole-3-acetic acid within 72 hours