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

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ClinicalTrials.gov Identifier: NCT03059862
Recruitment Status : Unknown
Verified December 2017 by McMaster University.
Recruitment status was:  Recruiting
First Posted : February 23, 2017
Last Update Posted : December 20, 2017
Sponsor:
Collaborators:
National Research Agency, France
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
McMaster University

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diet Modification Dietary Supplement: L-tryptophan Dietary Supplement: Placebo Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: All subjects will be following a standardized low-tryptophan diet and randomized to L-tryptophan supplements or placebo, for three weeks. After a 2 weeks washout period, subjects will crossover to the other arm.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: The Role of Tryptophan on Aryl Hydrocarbon Receptor Activation: a Randomized, Double Blind, Placebo-controlled, Crossover Design Pilot Trial
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : April 30, 2018
Estimated Study Completion Date : June 30, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Tryptophan

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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)

  6. 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteer between 18 and 75 years of age.

Exclusion Criteria:

  • Rome IV criteria for any functional gastrointestinal disorder.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03059862


Contacts
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Contact: Natalia Causada Calo, MD +19059020215 causadan@mcmaster.ca
Contact: Elena Verdu, MD, PhD 905.523.6048 verdue@mcmaster.ca

Locations
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Canada, Ontario
McMaster Health Sciences Centre Recruiting
Hamilton, Ontario, Canada, L8N3Z5
Contact: Natalia Causada Calo, MD    9059020215    causadan@mcmaster.ca   
Sub-Investigator: María Inés Pinto-Sánchez, MD         
Sub-Investigator: Elena Verdu, MD, PhD         
Sub-Investigator: Suzanne Hansen, Dietician         
Sub-Investigator: Natalia Causada Calo, MD         
Principal Investigator: Premysl Bercik, MD, PhD         
Sponsors and Collaborators
McMaster University
National Research Agency, France
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: Premysl Bercik, MD, PhD McMaster University, Department of Medicine, Division of Gastroenterology
More Information
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Additional Information:

Publications of Results:

Other Publications:

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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03059862    
Other Study ID Numbers: Aryl-IMMUNE
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by McMaster University:
immunity
Aryl-hydrocarbon receptor
immune homeostasis
microbiota
tryptophan
Additional relevant MeSH terms:
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Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs