Tryptophan Metabolism AlterationsTIARSCeDNCT05576038
Tryptophan for Impaired AhR Signaling in Celiac Disease
A study testing L-Tryptophan and Freedom SimpleCap Powder in people with Tryptophan Metabolism Alterations and Celiac Disease, run by McMaster University at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Tryptophan Metabolism Alterations, Celiac Disease
- What is being tested?
- L-Tryptophan and Freedom SimpleCap Powder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2022to 1 Jun 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
McMaster University
Hamilton, Ontario, L8N3Z5
David Armstrong
About this study
Official title: Restoration of Impaired Microbiota-mediated Aryl Hydrocarbon Receptor Signaling in Celiac Disease by Oral Tryptophan Supplementation: an Exploratory, Pilot Trial
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.
Read the 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.
- Conditions
- Tryptophan Metabolism Alterations, Celiac Disease
- Being tested
- L-Tryptophan, Freedom SimpleCap Powder
- Keywords
- Tryptophan, Celiac disease, Aryl Hydrocarbon Receptor
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-TryptophanDrug
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.
Freedom SimpleCap PowderDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Freedom SimpleCap Powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Celiac Symptom Index (CSI)
Change in CSI score; a 7-point decrease in CSI score indicates meaningful improvement.
Measured: 3 weeks
Secondary outcomes (4)
Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).
Change in PAGI-QoL score from baseline to week 3; an increase in score indicates an improvement in quality of life. PAGI-QoL score ranges from 0 to 5, 0 being the lowest and 5 being the highest.
Measured: 3 weeks
Hospital Anxiety and Depression Scale (HADS)
Change in the anxiety and depression scores for the HADS from baseline to week 3; a decrease in the scores indicate decreases in anxiety and depression respectively. The anxiety and depression scales score separately, each ranging from 0 to 21, 0 being the lowest and 21 being the highest.
Measured: 3 weeks
Gastrointestinal Symptoms Rating Scale (GSRS)
Change in GSRS score from baseline to week 3. Score ranges from 1-7; decrease in score indicates improvement.
Measured: 3 weeks
Intestinal indole production in the duodenum
Change in duodenal indole production from baseline to week 3
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start1 Dec 2022
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tryptophan Metabolism AlterationsStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Armstrong, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05576038
- Sponsor's protocol ID
- 14582
- Acronym
- TIARSCeD
- Status last verified
- Jan 2025
- First submitted
- 3 Oct 2022
- Last updated
- 10 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will not be shared among other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoration of Impaired Microbiota-mediated Aryl Hydrocarbon Receptor Signaling in Celiac Disease by Oral Tryptophan Supplementation: an Exploratory, Pilot Trial
- ClinicalTrials.gov ID
- NCT05576038
- Acronym / sponsor ID
- TIARSCeD / 14582
- Conditions
- Tryptophan Metabolism Alterations, Celiac Disease
- Keywords
- Tryptophan, Celiac disease, Aryl Hydrocarbon Receptor
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 12 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study
| Arm | Type | Receives |
|---|---|---|
| L-Tryptophan | Active comparator | Drug: L-TryptophanL-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. |
| Freedom SimpleCap Powder | Placebo comparator | Drug: Freedom SimpleCap Powder500 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 may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-TryptophanL-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-Tryptophan |
| Freedom SimpleCap PowderFreedom 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. | Drug | Freedom SimpleCap Powder |
Primary outcome
Measurement of Celiac Symptom Index (CSI)
Time frame: 3 weeks
Change in CSI score; a 7-point decrease in CSI score indicates meaningful improvement.
4 secondary outcomes
Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).
Time frame: 3 weeks
Hospital Anxiety and Depression Scale (HADS)
Time frame: 3 weeks
Gastrointestinal Symptoms Rating Scale (GSRS)
Time frame: 3 weeks
Intestinal indole production in the duodenum
Time frame: 3 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
- Individual participant dataSharing planned: No. Data will not be shared among other researchers.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-Tryptophan and Freedom SimpleCap Powder in people with Tryptophan Metabolism Alterations and Celiac Disease, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gaston H Rueda, MD (905 521-2100 ext. 21875, ruedag@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of Celiac Symptom Index (CSI) (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2025.