Clinical trial NCT05576038: Tryptophan for Impaired AhR Signaling in Celiac Disease
Official title: Restoration of Impaired Microbiota-mediated Aryl Hydrocarbon Receptor Signaling in Celiac Disease by Oral Tryptophan Supplementation: an Exploratory, Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tryptophan Metabolism Alterations
Celiac Disease
Keywords: Tryptophan
Celiac disease
Aryl Hydrocarbon Receptor
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2022-10-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Measurement of Celiac Symptom Index (CSI)
timeFrame: 3 weeks
Secondary outcomes:
measure: Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).
timeFrame: 3 weeks
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3 weeks
measure: Gastrointestinal Symptoms Rating Scale (GSRS)
timeFrame: 3 weeks
measure: Intestinal indole production in the duodenum
timeFrame: 3 weeks
Other outcomes:
measure: Duodenal mucosal villus-crypt ratio (VCR)
timeFrame: 3 weeks
measure: Aryl hydrocarbon Receptor (AhR) activation in the duodenum
timeFrame: 3 weeks
measure: Tissue transglutaminase IgA (tTG) titres
timeFrame: 3 weeks
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
References: