Clinical trial

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

Name

14582

Description

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.

Trial arms

Trial start

2022-12-01

Estimated PCD

2024-11-01

Trial end

2025-06-01

Status

Recruiting

Treatment

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.

Arms:

L-Tryptophan

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.

Arms:

Freedom SimpleCap Powder

Size

Primary endpoint

Measurement of Celiac Symptom Index (CSI)

3 weeks

Eligibility criteria

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Interventions will be blinded by McMaster University Central Pharmacy', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 50, 'type': 'ESTIMATED'}}

Updated at

2023-10-16

1 organization

Organization

McMaster University