Tryptophan for Celiac Disease

(TIARSCeD Trial)

Overseen By Gaston H Rueda, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Must not be taking: Antacids, Antibiotics, MAOIs, others

Disqualifiers: Diabetes, GI diseases, Surgery, others

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether L-tryptophan, a supplement, can help people with celiac disease who continue to experience symptoms despite following a gluten-free diet for over a year. Participants will receive either L-tryptophan or a placebo (a pill with no active ingredient) for three weeks to assess any improvement in their symptoms. This trial is best suited for individuals with biopsy-confirmed celiac disease who still have symptoms despite long-term adherence to a gluten-free diet. As an unphased trial, it offers a unique opportunity to contribute to understanding potential new treatments for celiac disease.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as acid anti-secretory and antacid medications, antibiotics, antibacterial agents, probiotics, lithium, and monoamine oxidase inhibitors (MAOIs). If you are on any of these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that L-tryptophan is generally safe for people. Earlier research indicates that doses between 8 to 15 grams per day are well tolerated. In this trial, the dose is much lower, at 3 grams per day, suggesting participants are likely to handle it well.

L-leucine is not part of this trial, so its safety does not need discussion here. While L-tryptophan appears safe, participants should consider their own health conditions and consult their doctor about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for celiac disease, which usually involve strict adherence to a gluten-free diet, L-Tryptophan offers a novel approach by targeting the condition with an amino acid supplement. Researchers are excited about L-Tryptophan because it's thought to potentially modulate the immune response, which could help reduce inflammation and alleviate symptoms for those with celiac disease. This is different from current options that primarily focus on dietary restrictions rather than addressing the underlying immune mechanism.

What evidence suggests that L-tryptophan might be an effective treatment for celiac disease?

Research suggests that L-tryptophan, one of the treatments under study in this trial, might help reduce symptoms of celiac disease, especially for those who don't improve on a gluten-free diet. Studies have shown that L-tryptophan may activate the aryl hydrocarbon receptor (AhR), which could enhance the immune system and possibly reduce inflammation related to celiac disease. Early findings indicate that tryptophan could be promising for managing symptoms like stomach pain and bloating in people who continue to have issues. While more research is needed, L-tryptophan offers a hopeful option for those still struggling with celiac symptoms. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with celiac disease who still have symptoms despite following a gluten-free diet for over a year. Participants must have confirmed celiac disease with specific tests and score above 40 on the Celiac Symptom Index. People taking certain medications, those with other autoimmune or systemic diseases, gastrointestinal issues besides benign conditions, recent participants in dietary studies, substance abusers, and individuals with lactose/fructose intolerance cannot join.

Inclusion Criteria

I have been diagnosed with celiac disease confirmed by a biopsy and blood test.

I still have celiac symptoms after a year on a gluten-free diet.

Exclusion Criteria

I do not have conditions like inflammatory bowel disease or type 1 diabetes.

You have problems with alcohol or drugs.

I do not have serious stomach or intestine diseases except for minor conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive L-tryptophan or placebo for 3 weeks, with dietary counseling and monitoring

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• L-Leucine
• L-Tryptophan
• Placebo

Trial Overview

The study is testing if L-Tryptophan supplements can help reduce symptoms of celiac disease that persist even after following a gluten-free diet. Half of the participants will receive L-Tryptophan while the other half will get a placebo without knowing which one they're taking (double-blind). The treatment period lasts for three weeks.

How Is the Trial Designed?

Group I: L-Tryptophan Active Control 1 Intervention

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.

Group II: Freedom SimpleCap Powder Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

The workshop highlighted that the upper intake limit for leucine in healthy humans may be around 500 mg/(kg · d), but more research is needed to establish a safe margin for the general population.

For tryptophan, while older studies indicated that doses of 8-15 g/d were well tolerated, there is a lack of recent human data, and animal studies have not yet provided a clear consensus on safe intake levels for humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of workshop discussions on establishing upper limits for amino acids with specific attention to available data for the essential amino acids leucine and tryptophan. Kimura, T., Bier, DM., Taylor, CL.[2023]

Celiac adults on a long-term gluten-free diet showed significant deficiencies in essential nutrients such as folates, vitamin E, iodine, calcium, and vitamin D, indicating a need for careful dietary monitoring.

Despite these deficiencies, the overall nutritional status of celiac patients was similar to that of healthy volunteers, suggesting that dietary habits in the general population may also contribute to these deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Status in Spanish Adults with Celiac Disease Following a Long-Term Gluten-Free Diet Is Similar to Non-Celiac. Ballestero-Fernández, C., Varela-Moreiras, G., Úbeda, N., et al.[2021]

Celiac disease is an autoimmune disorder triggered by gluten in genetically susceptible individuals, primarily associated with specific HLA haplotypes (DQ2 and DQ8), and can present in various forms including typical, atypical, silent, and latent.

Current diagnosis relies on histological changes in the small intestine, with serological tests like IgA anti-tissue transglutaminase showing high sensitivity (up to 98%) and specificity (around 96%), while future treatments may include gluten-degrading enzymes and immunotherapy as alternatives to the gluten-free diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiac disease: risk assessment, diagnosis, and monitoring. Setty, M., Hormaza, L., Guandalini, S.[2022]

In patients with active celiac disease, there is a significant increase in leucine and glutamine turnover, indicating heightened protein breakdown, which may contribute to their protein malnutrition status.

The study suggests that the increased renewal of intestinal epithelial cells plays a major role in whole-body protein turnover, highlighting the importance of glutamine as a fuel source for these cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-body protein metabolism assessed by leucine and glutamine kinetics in adult patients with active celiac disease. Messing, B., Dutra, SL., Thuillier, F., et al.[2019]

In a study involving Fischer 344 rats and B6C3F1 mice, L-Tryptophan showed little toxic effect, with minimal body weight loss and high survival rates in rats, indicating it is safe at the tested doses.

No significant increase in tumor incidence was found in rats, and while some hematopoietic tumors appeared in mice, they were not statistically significant, leading to the conclusion that L-Tryptophan is not carcinogenic under the study conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioassay of L-Tryptophan for Possible Carcinogenicity (CAS No. 73-22-3). [2020]

L-Tryptophan (L-Trp) is crucial for growth and can help prevent pellagra, making it an important nutrient, especially in underdeveloped countries.

Research suggests that the urinary excretory ratio of anthranilic acid to kynurenic acid could serve as a sensitive biomarker to predict the safe upper intake level of L-Trp, which is important for ensuring its safe use without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolites in the tryptophan degradation pathway might be useful to determine the tolerable upper intake level of tryptophan intake in rats. Shibata, K., Fukuwatari, T.[2023]

In a study of 11 untreated coeliac disease patients, most showed normal brain availability of the monoamine precursors tryptophan and tyrosine, suggesting that central monoamine metabolism may not be universally impaired in these individuals.

However, 4 patients with a history of major psychiatric illness exhibited reduced brain availability of tryptophan, indicating that these individuals may require special attention in managing depression related to coeliac disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain availability of monoamine precursors in adult coeliac disease. Hallert, C., Mårtensson, J., Allgén, LG.[2019]

After one year on a gluten-free diet, adult coeliac patients showed a 33% increase in key monoamine metabolites in their cerebrospinal fluid (CSF), indicating improved brain chemistry.

The study also found a 10% increase in tryptophan levels in CSF and noted improvements in the jejunal mucosa, suggesting that the previously low levels of these metabolites were likely due to poor intestinal absorption rather than genetic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in central monoamine metabolism in adult coeliac patients starting a gluten-free diet. Hallert, C., Sedvall, G.[2019]

Untreated children with coeliac disease have significantly lower plasma concentrations of tryptophan compared to both treated children and healthy controls, which may affect their mental health.

The reduced availability of tryptophan in untreated coeliac children could lead to decreased serotonin synthesis in the brain, potentially contributing to behavioral disorders such as depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. Hernanz, A., Polanco, I.[2019]

The study found that adults with untreated celiac disease have higher levels of pyridoxal 5'-phosphate, an active form of vitamin B6, in their cerebrospinal fluid, contradicting the expectation that vitamin B6 deficiency would inhibit serotonin metabolism.

Despite normal levels of tryptophan, the precursor for serotonin, the reduced serotonin turnover in these patients does not appear to be directly linked to vitamin B6 deficiency, suggesting that other factors may contribute to the mental health issues commonly seen in celiac disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High level of pyridoxal 5'-phosphate in the cerebrospinal fluid of adult celiac patients. Hallert, C., Allenmark, S., Larsson-Cohn, U., et al.[2018]

Celiac disease (CeD) is a complex immune-mediated condition influenced by gluten proteins, specific genetic factors (HLA-DQ2 and -DQ8), and various cofactors like intestinal microbiota, which can complicate its management beyond just a gluten-free diet.

Recent advancements in understanding CeD have led to promising new therapies currently in clinical trials, including gluten-degrading enzymes and cytokine therapies, which aim to improve patient outcomes and allow for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment. Verdu, EF., Schuppan, D.[2022]

L-tryptophan and its derivative 5-hydroxytryptophan may play a significant role in increasing serotonin synthesis, which could help in treating disorders like depression and irritable bowel syndrome.

Given that around 20% of patients with functional bowel disorders also have psychiatric issues, L-tryptophan could serve as a crucial link in understanding and managing these interconnected conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the implications of dietary tryptophan intake in patients with irritable bowel syndrome and psychiatric disorders. Agazzi, A., De Ponti, F., De Giorgio, R., et al.[2019]

Celiac disease affects about 1% of the U.S. population, with higher prevalence in individuals with a family history, highlighting the importance of genetic predisposition in its diagnosis and management.

Comprehensive nutritional management and proper diagnostic strategies, including serologic testing and HLA haplotypes, are crucial for effective treatment and monitoring of celiac disease, especially given its association with various other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies. McAllister, BP., Williams, E., Clarke, K.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10872053/

AN EXPLORATORY STUDY - PMC

The study aims were to: 1) determine whether tryptophan supplementation improves celiac specific symptoms in non-responders; and 2) if ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05576038

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 ...

3.

withpower.com

withpower.com/trial/phase-tryptophan-metabolism-alterations-9-2022-0df39

Tryptophan for Celiac Disease (TIARSCeD Trial)

Trial Overview The study is testing if L-Tryptophan supplements can help reduce symptoms of celiac disease that persist even after following a gluten-free diet.

4.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/full/10.1002/iid3.1354

The role of tryptophan metabolism and tolerogenic ...

This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD.

5.

clinicaltrials.eu

clinicaltrials.eu/inn/l-tryptophan/

L-Tryptophan: A Comprehensive Guide for Patients

The research aims to evaluate if L-Tryptophan supplementation can improve celiac-related symptoms by activating the aryl hydrocarbon receptor (AhR) pathway, ...

6.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT05576038/tryptophan-for-impaired-ahr-signaling-in-celiac-disease

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 ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4401736/

Essential Amino Acids in the Gluten-Free Diet and Serum in ...

Despite its potential adverse effect, intake and serum levels of essential amino acids were not related to major depression.