In Vivo Effects of Amylase Trypsin Inhibitors

NCT ID: NCT05157867

Last Updated: 2023-03-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-30
• Study Completion Date: 2024-09-30

Brief Summary

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.

Conditions

Non-Coeliac Wheat Sensitivity (NCWS); Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Amylase trypsin inhibitors (ATIs), then placebo

Test day 1: intraduodenal administration of amylase trypsin inhibitors (ATIs) isolated from Triticum aestivum (bread wheat), dissolved in physiological saline. After a wash-out period of 4-6 weeks, test day 2: intraduodenal administration of placebo (physiological saline).

Group Type: EXPERIMENTAL

Amylase trypsin inhibitors

Intervention Type: OTHER

Intraduodenal administration of amylase trypsin inhibitors (ATIs) isolated from Triticum aestivum (wheat), dissolved in physiological saline.

Placebo

Intervention Type: OTHER

Intraduodenal administration of placebo (physiological saline).

Placebo, then Amylase trypsin inhibitors

Test day 1: intraduodenal administration of placebo (physiological saline). After a wash-out period of 4-6 weeks, test day 2: intraduodenal administration of amylase trypsin inhibitors (ATIs) isolated from Triticum aestivum (bread wheat), dissolved in physiological saline.

Group Type: EXPERIMENTAL

Amylase trypsin inhibitors

Intervention Type: OTHER

Intraduodenal administration of amylase trypsin inhibitors (ATIs) isolated from Triticum aestivum (wheat), dissolved in physiological saline.

Placebo

Intervention Type: OTHER

Intraduodenal administration of placebo (physiological saline).

Interventions

Amylase trypsin inhibitors

Intraduodenal administration of amylase trypsin inhibitors (ATIs) isolated from Triticum aestivum (wheat), dissolved in physiological saline.

Intervention Type: OTHER

Placebo

Intraduodenal administration of placebo (physiological saline).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Based on medical history and previous self-admitted examination, no gastrointestinal complaints and/or disease can be defined.

2. Age between 18 and 65 years.

3. Body Mass Index (BMI) between 20 and 30 kg/m2.

Exclusion Criteria

1. History of severe cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator.

2. Use of medication, including vitamin supplementation, pre- and probiotic supplementation, except oral contraceptives, within 14 days prior to testing.

3. Administration of investigational drugs or participation in any scientific intervention study, which may interfere with this study (to be decided by the principal investigator), in the 180 days prior to the study.

4. Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principal investigator).

5. Pregnancy, lactation.

6. Excessive alcohol consumption (> 14 alcoholic consumptions per week).

7. Smoking.

8. Drug use.

9. Blood donation within 3 months before or after the study period.

10. Self-admitted HIV-positive state.

11. Plan to lose weight or follow a specific diet (e.g. weight loss or gluten-free diet) within the study period.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daisy MAE Jonkers, Prof, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Central Contacts

Marlijne CG de Graaf, MSc

Role: CONTACT

m.degraaf@maastrichtuniversity.nl

+31(0)433884237

Other Identifiers

NL77666.608.21

Identifier Type: -

Identifier Source: org_study_id