Tryptophan for Impaired AhR Signaling in Celiac Disease

NCT05576038 | Recruiting DMC

• 1 other identifier: 14582
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tryptophan Metabolism Alterations; Celiac Disease

Keywords

Tryptophan; Celiac disease; Aryl Hydrocarbon Receptor

Outcome Measures

Primary Outcomes (1)

• Measurement of Celiac Symptom Index (CSI)

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

  3 weeks

Secondary Outcomes (4)

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

  3 weeks

• Hospital Anxiety and Depression Scale (HADS)

  3 weeks

• Gastrointestinal Symptoms Rating Scale (GSRS)

  3 weeks

• Intestinal indole production in the duodenum

  3 weeks

Other Outcomes (3)

• Duodenal mucosal villus-crypt ratio (VCR)

  3 weeks

• Aryl hydrocarbon Receptor (AhR) activation in the duodenum

  3 weeks

• Tissue transglutaminase IgA (tTG) titres

  3 weeks

Study Arms (2)

L-Tryptophan

ACTIVE COMPARATOR

L-tryptophan\* supplements (Tryptan, Valeant Canada LP): each treatment capsule contains 500 mg of L-Tryptophan; talc and magnesium stearate. Study participants will be instructed to take 2 x 500 mg capsules (1000 mg) every 8 hrs, three times a day. (total daily dose: 3000 mg) for a total of 3 weeks. Instructions will be printed on the label of the pill container.

Drug: L-Tryptophan

Freedom SimpleCap Powder

PLACEBO COMPARATOR

500 mg of SimpleCap Powder. Study participants will be instructed to take 2 x 500 mg capsules (1000 mg) every 8 hrs, three times a day. (total daily dose: 3000 mg) for a total of 3 weeks. Instructions will be printed on the label of the pill container.

Drug: Freedom SimpleCap Powder

Interventions

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.

L-Tryptophan

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.

Freedom SimpleCap Powder

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

McMaster University

Hamilton, Ontario, L8N3Z5, Canada

RECRUITING

MeSH Terms

Conditions

Celiac Disease

Interventions

Tryptophan

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Central Study Contacts

Gaston H Rueda, MD

CONTACT

905 521-2100; ruedag@mcmaster.ca

Utkarshini N Kirtikar, MSc

CONTACT

905 521-2100; kirtikau@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Interventions will be blinded by McMaster University Central Pharmacy
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 12, 2022
• Study Start: December 1, 2022
• Primary Completion: April 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)