Tryptophan for Impaired AhR Signaling in Celiac Disease
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.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
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|Eligible Ages||18 Years - 75 Years|
- - 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.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Principal Investigator Affiliation||N/A|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Overall Status||Not yet recruiting|
The disease, disorder, syndrome, illness, or injury that is being studied.
|Tryptophan Metabolism Alterations, Celiac Disease|
At Visit 1, consented participants will receive study instructions and be randomized 1:1 to L-tryptophan or placebo (L-leucine). 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 esophago-gastroduodenoscopy 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 by a validated questionnaire and interview with the dietitian.
Active Comparator: L-Tryptophan
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.
Placebo Comparator: L-Leucine
500 mg of L-Leucine. 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
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: - L-Leucine
L-leucine is an essential branched-chain amino acid (BCAA) required for protein synthesis. Most dietary leucine is metabolized in the liver, muscle and intestinal tissues. Currently, there is no evidence that leucine plays a role in maintaining intestinal integrity. Furthermore, leucine has no effect on the tryptophan-AhR-related metabolic pathway. When leucine was used, in our preliminary study, as a placebo comparator to L-tryptophan in healthy subjects it did not activate the AhR pathway and it did not exhibit any therapeutic effect. Thus, leucine will be an appropriate placebo comparator for this study.
This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:
Gaston H Rueda, MD
For additional contact information, you can also visit the trial on clinicaltrials.gov.