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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

Tracking Information
First Submitted Date  ICMJE January 18, 2017
First Posted Date  ICMJE February 23, 2017
Last Update Posted Date December 20, 2017
Actual Study Start Date  ICMJE November 1, 2017
Estimated Primary Completion Date April 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Role of Dietary Tryptophan on Aryl Hydrocarbon Receptor Activation
Official Title  ICMJE The Role of Tryptophan on Aryl Hydrocarbon Receptor Activation: a Randomized, Double Blind, Placebo-controlled, Crossover Design Pilot Trial
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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Diet Modification
Intervention  ICMJE
  • Dietary Supplement: L-tryptophan
    3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.
  • Dietary Supplement: Placebo
    A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.
Study Arms  ICMJE
  • 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).
    Intervention: Dietary Supplement: L-tryptophan
  • Placebo Comparator: Low-tryptophan diet and placebo
    Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + placebo.
    Intervention: Dietary Supplement: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 16, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2018
Estimated Primary Completion Date April 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy volunteer between 18 and 75 years of age.

Exclusion Criteria:

  • Rome IV criteria for any functional gastrointestinal disorder.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03059862
Other Study ID Numbers  ICMJE Aryl-IMMUNE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party McMaster University
Study Sponsor  ICMJE McMaster University
Collaborators  ICMJE
  • National Research Agency, France
  • Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Premysl Bercik, MD, PhD McMaster University, Department of Medicine, Division of Gastroenterology
PRS Account McMaster University
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP