NCT05157867: ATI

In Vivo Effects of Amylase Trypsin Inhibitors From Wheat in the Human Gut: Proof of Cause of Non-coeliac Wheat Sensitivity in Irritable Bowel Syndrome?

Status unknown NA Last updated 24 March 2023

What this trial tests

NA trial testing Amylase trypsin inhibitors in Non-Coeliac Wheat Sensitivity (NCWS) in 8 participants. Status unknown.

Timeline

1 September 2023

Primary endpoint
1 September 2024

1 September 2024

Quick facts

Lead sponsor	Maastricht University
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	basic science
Enrollment	8
Start date	1 September 2023
Primary completion	1 September 2024
Estimated completion	1 September 2024

Drugs / interventions tested

• Amylase trypsin inhibitors
• Placebo

Conditions studied

• Non-Coeliac Wheat Sensitivity (NCWS) — all drugs for Non-Coeliac Wheat Sensitivity (NCWS) →
• Irritable Bowel Syndrome — all drugs for Irritable Bowel Syndrome →

Sponsor

Maastricht University

Who can join

Adults 18 to 65, any sex, with Non-Coeliac Wheat Sensitivity (NCWS) or Irritable Bowel Syndrome. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Difference in gene expression associated with intestinal barrier function, measured in duodenal biopsies collected after intervention with ATIs or placebo
  Time frame: Biopsies will be collected 2 hours after administration of ATIs or placebo, on two separate test days. The test days are separated by a wash-out period of 4-6 weeks.
  Gene expression associated with intestinal barrier function, such as gene expression of tight junction and adherens junction proteins: e.g. peri-junctional Factin, myosin, ZO-1, claudin-3, occluding, myosin light chain kinase, phosphorylated myosin light chain, E-cadherin. Duodenal biopsies will be obtained using upper gastrointestinal endoscopy.

Sponsor's own description

Wheat is the most important staple food consumed in the Western world and provides beneficial health effects and functional properties. Nevertheless, an increasing proportion of the general population is avoiding or reducing its consumption of wheat products due to self-reported gastrointestinal (GI) symptoms, such as patients with non-coeliac wheat sensitivity (NCWS) and/or irritable bowel syndrome (IBS). There is increasing evidence that the amylase trypsin inhibitors (ATIs), accounting for up to 15% of wheat proteins, play a role in the symptom generation in NCWS and IBS. In vitro studies showed ATIs can induce an innate immune response via direct interaction with the toll-like receptor 4 (TLR4), activating the TLR4-MD2-CD14 complex with subsequent release of pro-inflammatory cytokines. These results were confirmed in mice. Furthermore, in mice ATIs triggered intestinal epithelial lymphocytosis and barrier dysfunction, and modified microbiota composition and metabolism. Thus far, there have been no placebo-controlled studies investigating these effects of isolated ATIs in human subjects. Understanding the role of ATIs in symptom generation in NCWS and IBS patients is important to provide these patients with appropriate dietary advice, improving their quality of life and decreasing their risk of nutritional deficiencies.

The investigators aim to perform a proof-of-concept study to assess the effect of ATIs on the intestinal barrier and immune function in healthy volunteers. The investigators hypothesise that the ATIs either directly affect the intestinal barrier function, or indirectly by activating an immune response via TLR4.

The study conforms a randomized, double-blind, placebo-controlled, cross-over design, using healthy human volunteers (male and female), 18-65 years old. Volunteers will each undergo two test days, separated by a wash-out period of at least 4 weeks. At the test day, volunteers receive either isolated ATIs or placebo (physiological saline), ingested using a nasogastric intraduodenal feeding catheter.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.