search
Back to results

Tryptophan for Impaired AhR Signaling in Celiac Disease (TIARSCeD)

Primary Purpose

Tryptophan Metabolism Alterations, Celiac Disease

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
L-Tryptophan
Freedom SimpleCap Powder
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tryptophan Metabolism Alterations focused on measuring Tryptophan, Celiac disease, Aryl Hydrocarbon Receptor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • McMaster UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

L-Tryptophan

Freedom SimpleCap Powder

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Measurement of Celiac Symptom Index (CSI)
Change in CSI score; a 7-point decrease in CSI score indicates meaningful improvement.

Secondary Outcome Measures

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.
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.
Gastrointestinal Symptoms Rating Scale (GSRS)
Change in GSRS score from baseline to week 3. Score ranges from 1-7; decrease in score indicates improvement.
Intestinal indole production in the duodenum
Change in duodenal indole production from baseline to week 3

Full Information

First Posted
October 3, 2022
Last Updated
October 12, 2023
Sponsor
McMaster University
search

1. Study Identification

Unique Protocol Identification Number
NCT05576038
Brief Title
Tryptophan for Impaired AhR Signaling in Celiac Disease
Acronym
TIARSCeD
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tryptophan Metabolism Alterations, Celiac Disease
Keywords
Tryptophan, Celiac disease, Aryl Hydrocarbon Receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized controlled trial: double-blinded, placebo controlled exploratory study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Interventions will be blinded by McMaster University Central Pharmacy
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-Tryptophan
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Freedom SimpleCap Powder
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
L-Tryptophan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Freedom SimpleCap Powder
Intervention Description
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.
Primary Outcome Measure Information:
Title
Measurement of Celiac Symptom Index (CSI)
Description
Change in CSI score; a 7-point decrease in CSI score indicates meaningful improvement.
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).
Description
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.
Time Frame
3 weeks
Title
Hospital Anxiety and Depression Scale (HADS)
Description
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.
Time Frame
3 weeks
Title
Gastrointestinal Symptoms Rating Scale (GSRS)
Description
Change in GSRS score from baseline to week 3. Score ranges from 1-7; decrease in score indicates improvement.
Time Frame
3 weeks
Title
Intestinal indole production in the duodenum
Description
Change in duodenal indole production from baseline to week 3
Time Frame
3 weeks
Other Pre-specified Outcome Measures:
Title
Duodenal mucosal villus-crypt ratio (VCR)
Description
Change in the duodenal mucosal VCR from baseline to week 3; an increase in the mucosal VCR ratio indicates decreased mucosal injury
Time Frame
3 weeks
Title
Aryl hydrocarbon Receptor (AhR) activation in the duodenum
Description
Change in duodenal mucosal AhR activation from baseline to week 3
Time Frame
3 weeks
Title
Tissue transglutaminase IgA (tTG) titres
Description
Change in tTG titers from baseline to week 3; a decrease in tTG titres is associated with decreased gluten exposure and, hence, with decreased celiac disease activity
Time Frame
3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gaston H Rueda, MD
Phone
905 521-2100
Ext
21875
Email
ruedag@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Utkarshini N Kirtikar, MSc
Phone
905 521-2100
Ext
21875
Email
kirtikau@mcmaster.ca
Facility Information:
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N3Z5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Armstrong

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data will not be shared among other researchers.

Learn more about this trial

Tryptophan for Impaired AhR Signaling in Celiac Disease

We'll reach out to this number within 24 hrs