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
|Condition or disease||Intervention/treatment||Phase|
|Diet Modification||Dietary Supplement: L-tryptophan Dietary Supplement: Placebo||Not Applicable|
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 (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|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)|
|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|
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.
- 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.
- 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)
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
|Contact: Natalia Causada Calo, MDfirstname.lastname@example.org|
|Contact: Elena Verdu, MD, PhDemail@example.com|
|McMaster Health Sciences Centre||Recruiting|
|Hamilton, Ontario, Canada, L8N3Z5|
|Contact: Natalia Causada Calo, MD 9059020215 firstname.lastname@example.org|
|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|
|Principal Investigator:||Premysl Bercik, MD, PhD||McMaster University, Department of Medicine, Division of Gastroenterology|