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.

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.

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

Data will not be shared among other researchers.

Interventions will be blinded by McMaster University Central Pharmacy