Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
Primary Purpose
Healthy, Chronic Kidney Diseases
Status
Completed
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Doctor's Best L-Tryptophan
Sponsored by
About this trial
This is an interventional basic science trial for Healthy
Eligibility Criteria
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
Sites / Locations
- Taipei Tzu Chi Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tryptophan loading
Arm Description
All participants are introduced to receive tryptophan loading test.
Outcomes
Primary Outcome Measures
Indoxyl sulfate
serum and urine indoxyl sulfate concentration measurement
Secondary Outcome Measures
Indole-3-acetic acid
serum and urine Indole-3-acetic acid concentration measurement
Full Information
NCT ID
NCT04117191
First Posted
September 29, 2019
Last Updated
December 8, 2019
Sponsor
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04117191
Brief Title
Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
Official Title
Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
November 30, 2019 (Actual)
Study Completion Date
November 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Chronic Kidney Diseases
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
All the participants would be introduced to receive 2g tryptophan loading for exploring serum and urine indoxyl sulfate concentration.
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tryptophan loading
Arm Type
Experimental
Arm Description
All participants are introduced to receive tryptophan loading test.
Intervention Type
Dietary Supplement
Intervention Name(s)
Doctor's Best L-Tryptophan
Intervention Description
2g tryptophan loading once
Primary Outcome Measure Information:
Title
Indoxyl sulfate
Description
serum and urine indoxyl sulfate concentration measurement
Time Frame
the area under curve of serum and urine indoxyl sulfate within 72 hours
Secondary Outcome Measure Information:
Title
Indole-3-acetic acid
Description
serum and urine Indole-3-acetic acid concentration measurement
Time Frame
the area under curve of serum and urine Indole-3-acetic acid within 72 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ting-Yun Lin, MD.
Organizational Affiliation
Taichung Tzu Chi Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Taipei Tzu Chi Hospital
City
New Taipei City
ZIP/Postal Code
231
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
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