NCT03059862

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2017

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 18, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

February 23, 2017

Completed
8 months until next milestone

Study Start

First participant enrolled

November 1, 2017

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2018

Completed
Last Updated

April 13, 2023

Status Verified

April 1, 2023

Enrollment Period

6 months

First QC Date

January 18, 2017

Last Update Submit

April 11, 2023

Conditions

Diet Modification

Keywords

immunityAryl-hydrocarbon receptorimmune homeostasismicrobiotatryptophan

Outcome Measures

Primary Outcomes (1)

  • AHR activation levels in stool and duodenal content.

    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 Outcomes (6)

  • Bacterial and fungal microbiota composition in stool, duodenum and rectum/sigmoid biopsies.

    Three weeks

  • Tryptophan metabolites levels, including host and bacterial catabolites, in blood, urine and stool.

    Three weeks

  • mRNA levels in duodenal and rectum/sigmoid biopsies.

    three weeks

  • Cytokines in serum.

    three weeks.

  • Gastrointestinal symptoms

    three weeks.

  • +1 more secondary outcomes

Study Arms (2)

Low-tryptophan diet and L-tryptophan.

EXPERIMENTAL

Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + L-tryptophan supplements (3 g/day).

Dietary Supplement: L-tryptophan

Low-tryptophan diet and placebo

PLACEBO COMPARATOR

Standardized low-tryptophan diet (500-1000 mg of L-tryptophan and 1800 kcal) + placebo.

Dietary Supplement: Placebo

Interventions

L-tryptophanDIETARY_SUPPLEMENT

3 g/day of L-tryptophan added to the standardized low-tryptophan diet. Duration: 3 weeks.

Low-tryptophan diet and L-tryptophan.
PlaceboDIETARY_SUPPLEMENT

A placebo will be added to the standardized low-tryptophan diet. Duration: 3 weeks.

Low-tryptophan diet and placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy volunteer between 18 and 75 years of age.

You may not qualify if:

  • Rome IV criteria for any functional gastrointestinal disorder.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

McMaster Health Sciences Centre

Hamilton, Ontario, L8N3Z5, Canada

Location

Related Publications (11)

  • Barouki R, Coumoul X, Fernandez-Salguero PM. The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett. 2007 Jul 31;581(19):3608-15. doi: 10.1016/j.febslet.2007.03.046. Epub 2007 Mar 30.

    PMID: 17412325BACKGROUND

  • Behnsen J, Raffatellu M. Keeping the peace: aryl hydrocarbon receptor signaling modulates the mucosal microbiota. Immunity. 2013 Aug 22;39(2):206-7. doi: 10.1016/j.immuni.2013.08.012.

    PMID: 23973218BACKGROUND

  • Bender DA. Biochemistry of tryptophan in health and disease. Mol Aspects Med. 1983;6(2):101-97. doi: 10.1016/0098-2997(83)90005-5. No abstract available.

    PMID: 6371429BACKGROUND

  • Cynober L, Bier DM, Kadowaki M, Morris SM Jr, Elango R, Smriga M. Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly. J Nutr. 2016 Dec;146(12):2652S-2654S. doi: 10.3945/jn.115.228478. Epub 2016 Nov 9.

    PMID: 27934658BACKGROUND

  • Hubbard TD, Murray IA, Bisson WH, Lahoti TS, Gowda K, Amin SG, Patterson AD, Perdew GH. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep. 2015 Aug 3;5:12689. doi: 10.1038/srep12689.

    PMID: 26235394BACKGROUND

  • Kiss EA, Vonarbourg C, Kopfmann S, Hobeika E, Finke D, Esser C, Diefenbach A. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science. 2011 Dec 16;334(6062):1561-5. doi: 10.1126/science.1214914. Epub 2011 Oct 27.

    PMID: 22033518BACKGROUND

  • Kiss EA, Vonarbourg C. Aryl hydrocarbon receptor: a molecular link between postnatal lymphoid follicle formation and diet. Gut Microbes. 2012 Nov-Dec;3(6):577-82. doi: 10.4161/gmic.21865. Epub 2012 Aug 22.

    PMID: 22909905BACKGROUND

  • Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF, Wilhelm C, Veldhoen M. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell. 2011 Oct 28;147(3):629-40. doi: 10.1016/j.cell.2011.09.025. Epub 2011 Oct 13.

    PMID: 21999944BACKGROUND

  • Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D'Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013 Aug 22;39(2):372-85. doi: 10.1016/j.immuni.2013.08.003.

    PMID: 23973224BACKGROUND

  • Qiu J, Heller JJ, Guo X, Chen ZM, Fish K, Fu YX, Zhou L. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2012 Jan 27;36(1):92-104. doi: 10.1016/j.immuni.2011.11.011. Epub 2011 Dec 15.

    PMID: 22177117BACKGROUND

  • Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102. Epub 2016 May 9.

    PMID: 27158904RESULT

MeSH Terms

Interventions

Tryptophan

Intervention Hierarchy (Ancestors)

Amino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Study Officials

  • Premysl Bercik, MD, PhD

    McMaster University, Department of Medicine, Division of Gastroenterology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
CROSSOVER
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 18, 2017

First Posted

February 23, 2017

Study Start

November 1, 2017

Primary Completion

April 30, 2018

Study Completion

June 30, 2018

Last Updated

April 13, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)