The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation (Aryl-IMMUNE)

April 11, 2023 updated by: McMaster University

The Role of Tryptophan on Aryl Hydrocarbon Receptor Activation: a Randomized, Double Blind, Placebo-controlled, Crossover Design Pilot Trial

This study evaluates the role of dietary L-tryptophan, an essential amino acid, in the activation of a specific cellular component: the aryl hydrocarbon receptor.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor implicated in a range of key cellular events. In the gut, AHR is crucial for maintaining intestinal barrier immune homeostasis. The physiology of the AHR, however, is not completely understood; its precise gut luminal activators and functional consequences are unknown.

Some AHR ligands originate from the diet. Commensals play crucial roles in metabolizing tryptophan and other amino acids such as tyrosine, with the subsequent production of tryptophan metabolites. Previous studies show that inflammatory bowel disease (IBD) patients have impaired production of AHR agonists by the microbiota. Furthermore, dietary supplementation with tryptophan ameliorates clinical parameters of colitis in rodent models. Whether these findings translate into human pathophysiology has not been explored.

In the present study, the investigators will evaluate the effect of high- versus low-tryptophan diet on AHR activation in healthy participants. Briefly, participants will be instructed to follow a standardized low-tryptophan diet and will be randomized to a 3-week L-tryptophan supplement or placebo. Later, after a 2-week washout period, participants will crossover to the other arm. In addition, the effect of tryptophan and microbiota-derived metabolites on AHR activation will be analyzed.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N3Z5
        • McMaster Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy volunteer between 18 and 75 years of age.

Exclusion Criteria:

  • Rome IV criteria for any functional gastrointestinal disorder.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low-tryptophan diet and L-tryptophan.
Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + L-tryptophan supplements (3 g/day).
Dietary supplement: L-tryptophan
3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.
Placebo Comparator: Low-tryptophan diet and placebo
Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + placebo.
Dietary supplement: Placebo
A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AHR activation levels in stool and duodenal content.
Time Frame: three weeks
Changes in AHR activation levels will be assessed in stool and duodenal samples before and after the intervention (high- and low-tryptophan diets) using an AHR cell-reporter line.
three weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacterial and fungal microbiota composition in stool, duodenum and rectum/sigmoid biopsies.
Time Frame: Three weeks
Changes in bacterial and fungal microbiota composition will be assessed before and after the intervention in stool samples, duodenum and rectum biopsies.
Three weeks
Tryptophan metabolites levels, including host and bacterial catabolites, in blood, urine and stool.
Time Frame: Three weeks
Changes in tryptophan metabolites leves will be compared before and after the intervention, in blood, urine and stool samples.
Three weeks
mRNA levels in duodenal and rectum/sigmoid biopsies.
Time Frame: three weeks
Changes in mRNA levels in duodenal and rectum/sigmoid biopsies will be assessed before and after the intervention.
three weeks
Cytokines in serum.
Time Frame: three weeks.
Changes in cytokines in the serum (IL-22, IL-6, IL-2, IL-10, IL-12p70, IL-23p19, IFNγ, TNFα and CRP will be measured by ELISA in cell culture supernatants after stimulation with LPS, curdlan and ConA ) will be measured before and after the intervention and patients will be grouped into two categories for each measurement: high vs. low, according to the cutoff reference test value for each of the cytokines.
three weeks.
Gastrointestinal symptoms
Time Frame: three weeks.
Changes in gastrointestinal symptoms before and after the intervention will be assessed using a validated questionnaire (The Gastrointestinal Symptoms Rating Scale)
three weeks.
Mood
Time Frame: three weeks
Changes in mood before and after the intervention will be assessed using a validated questionnaire (Hospital anxiety and depression scale)
three weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)
National Research Agency, France

Investigators

  • Principal Investigator: Premysl Bercik, MD, PhD, McMaster University, Department of Medicine, Division of Gastroenterology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2017

Primary Completion (Actual)

April 30, 2018

Study Completion (Actual)

June 30, 2018

Study Registration Dates

First Submitted

January 18, 2017

First Submitted That Met QC Criteria

February 16, 2017

First Posted (Actual)

February 23, 2017

Study Record Updates

Last Update Posted (Estimate)

April 13, 2023

Last Update Submitted That Met QC Criteria

April 11, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Aryl-IMMUNE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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