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NCT Number: NCT05576038

Tryptophan for Impaired AhR Signaling in Celiac Disease

This is a prospective, randomized, double-blind, placebo-controlled exploratory trial to evaluate the effect of L-tryptophan supplementation on celiac-related symptoms in individuals who have biopsy-confirmed celiac disease (CeD) and symptoms non-responsive to a gluten-free diet (GFD). Fifty participants, aged 18 to 75 years, who self-report persistent CeD-related symptoms despite taking a GFD for more than 1 year and who score > 40 on the Celiac Symptom Index (CSI) will be randomized to receive L-tryptophan or placebo for 3 weeks.

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Key information

Conditions

Tryptophan Metabolism Alterations Celiac Disease Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

McMaster University

Hamilton, Ontario, L8N3Z5, Canada

Location status: Recruiting

Location contact

David Armstrong

CONTACT

About this study

At Visit 1, consented participants will receive study instructions and be randomized 1:1 to L-tryptophan or placebo (SimpleCap). A dietitian will counsel all 50 participants on how to maintain a low tryptophan, gluten-free diet. This diet provides an adequate intake of protein (50 g/day) and energy (1800 kcal/day) while limiting the consumption of high tryptophan-containing foods. Study participants will receive all their intervention capsules at Visit 1 to be taken for 3 weeks, starting the day after Visit 2. At Visits 2 and 3, just before and after the intervention, participants will complete dietary and symptom questionnaires, provide blood, stool, and urine samples, and undergo upper endoscopy to obtain aspirates from the second part of the duodenum, using a sterile catheter followed by six duodenal biopsies, 2 from the first part (bulb) and 4 from the second part of the duodenum. Dietary compliance will be assessed 3-day recalls which will further be analysed by using ESHA Food Processor, a Nutritional Analysis Software.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18 and 75 years of age
  • Celiac disease (CeD) diagnosis: Individuals with histological and serological evidence of CeD serology (positive biopsy and anti-tTG IgA)
  • Persistent CeD related symptoms (>40 on the Celiac Symptom Index) despite >1 year of a gluten free diet (GFD)

Exclusion criteria

  • Acid anti-secretory and antacid medications
  • Antibiotics, antibacterial agents or probiotics, currently, or within the last 8 weeks
  • Current organic gastrointestinal or other autoimmune diseases, such as inflammatory bowel disease or diabetes mellitus (type 1)
  • Lactose and/or fructose intolerance
  • History of bariatric surgery, fundoplication or gastrectomy (partial or complete)
  • Connective tissue disease
  • Concurrent organic GI pathology other than benign polyps, haemorrhoids, lipomas, Helicobacter pylori infection, diverticulosis and melanosis coli
  • Chronic treatment with high dose opioids
  • Alcohol or drug abuse
  • Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be a risk or that could interfere with data collection
  • Allergy or sensitivity to any component of the study medication or placebo
  • Use of lithium and monoamine oxidase inhibitors (MAOIs)
  • Participation in another dietary treatment study within the last 4 weeks

Treatment and study plan

L-Tryptophan

Drug

L-tryptophan is an essential amino acid responsible for activating the aryl hydrocarbon receptor (AhR). Dietary tryptophan is metabolized by the gut microbiota producing several 'indoles' such as (indole-3-aldehyde (IAld), indole-3-acetic acid (IAA), indole-3 propionic acid (IPA), indole-3-acetaldehyde (IAAld), indole-3-lactic acid (ILA) and indole-acrylic acid) and tryptamine, which are ligands for the AhR, a nuclear transcription factor involved in activating target genes responsible for maintaining gut integrity. Prior literature suggests that patients with active celiac disease have a lower functional capacity to produce these AhR ligands, which further impairs the AhR pathway. Hence, the aim of this study is to assess the effects of tryptophan supplementation in patients with celiac disease, non-responsive to a GFD for more than 1 year compared with the effects of an inactive, placebo comparator, L-leucine.

Freedom SimpleCap Powder

Drug

Freedom SimpleCap Powder is a high functionality capsule and tablet excipient composite comprised of filler, glidant, disintegrant and lubricant (ingredients include: Microcrystalline Cellulose, Silicon Dioxide Colloidal, Sodium Starch Glycolate, Sodium Stearyl Fumarate). This capsule is dye, lactose and gluten free and will not interfere with the AhR pathway. Freedom SimpleCap Powder makes oral capsule formulation convenient, quick and simple Thus, this SimpleCap Powder will be an appropriate placebo comparator for this study.

Primary outcomes

  1. Measurement of Celiac Symptom Index (CSI)

    Time frame: 3 weeks

    Change in CSI score; a 7-point decrease in CSI score indicates meaningful improvement.

Secondary outcomes

  1. Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).

    Time frame: 3 weeks

    Change in PAGI-QoL score from baseline to week 3; an increase in score indicates an improvement in quality of life. PAGI-QoL score ranges from 0 to 5, 0 being the lowest and 5 being the highest.

  2. Hospital Anxiety and Depression Scale (HADS)

    Time frame: 3 weeks

    Change in the anxiety and depression scores for the HADS from baseline to week 3; a decrease in the scores indicate decreases in anxiety and depression respectively. The anxiety and depression scales score separately, each ranging from 0 to 21, 0 being the lowest and 21 being the highest.

  3. Gastrointestinal Symptoms Rating Scale (GSRS)

    Time frame: 3 weeks

    Change in GSRS score from baseline to week 3. Score ranges from 1-7; decrease in score indicates improvement.

  4. Intestinal indole production in the duodenum

    Time frame: 3 weeks

    Change in duodenal indole production from baseline to week 3

Other outcomes

  1. Duodenal mucosal villus-crypt ratio (VCR)

    Time frame: 3 weeks

    Change in the duodenal mucosal VCR from baseline to week 3; an increase in the mucosal VCR ratio indicates decreased mucosal injury

  2. Aryl hydrocarbon Receptor (AhR) activation in the duodenum

    Time frame: 3 weeks

    Change in duodenal mucosal AhR activation from baseline to week 3

  3. Tissue transglutaminase IgA (tTG) titres

    Time frame: 3 weeks

    Change in tTG titers from baseline to week 3; a decrease in tTG titres is associated with decreased gluten exposure and, hence, with decreased celiac disease activity

Study contacts

Contact information is provided by the study sponsor or research team.

Gaston H Rueda, MD

CONTACT

[email protected]

905 521-2100 ext. 21875

Utkarshini N Kirtikar, MSc

CONTACT

[email protected]

905 521-2100 ext. 21875

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Registry information

Official study title

Restoration of Impaired Microbiota-mediated Aryl Hydrocarbon Receptor Signaling in Celiac Disease by Oral Tryptophan Supplementation: an Exploratory, Pilot Trial

Acronym: TIARSCeD

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Oct 12, 2022
Registry last updated
Jan 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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