NCT05576038

Tryptophan for Impaired AhR Signaling in Celiac Disease

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: McMaster University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Tryptophan Metabolism Alterations
• Celiac Disease

Interventions

Type	Name	Description
DRUG	L-Tryptophan	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.
DRUG	Freedom SimpleCap Powder	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.

Timeline

• Start date: 2022-12-01
• Primary completion: 2025-04-01
• Completion: 2025-06-01
• First posted: 2022-10-12
• Last updated: 2025-01-10

Locations

1 site across 1 country: Canada