Effect of AN-PEP enzyme on the effects of gluten ingestion in patients with coeliac disease

Rationale:

Coeliac disease is an autoimmune disorder of the small bowel and is caused by a reaction to a gluten protein found in wheat. Gluten proteins are resistant to degradation in the gastrointestinal tract.

The AN-PEP enzyme was shown to degrade gluten in an in vitro digestion model.

Objectives:

Determine whether AN-PEP enzyme is effective in mitigating the effects of gluten ingestion in patients with celiac disease

Study Design:

Randomised double-blinded semi-cross-over design

Patients:

Fourteen patients with coeliac disease, 18-70 years old

Treatments:

This study consists of three 14-d periods.

Period 1: Patients are given a food product containing 8 g of wheat protein, to which AN-PEP is added, once daily for 14 d.
Period 2: Wash-out period of 14 d. During this period patients will consume a gluten-free diet.

Period 3: Patients who are negative for coeliac disease symptoms during the 1st period will be randomised across two groups. Both groups receive a food product containing 8 g of wheat protein once daily for 14 d. One group receives additional AN-PEP with the gluten meal whereas the other groups receives the placebo.

- Primary study parameters:

Small intestinal biopsy material will be analysed for the following:

1. Histopathological changes according to the Modified Marsh criteria

2. The presence and activity of gluten reactive T cells isolated from biopsies

3. The immunophenotype of lymphocytes (IEL and LPL) isolated from biopsies

- Secondary study parameters:

Peripheral blood samples will be analysed for the following:

1. The presence and activity of gluten reactive T cells

2. The presence of coeliac disease specific antibodies (EMA, tTGA)

3. The presence of coeliac disease- associated clinical symptoms based on a quality of life questionnaire

Determine whether AN-PEP enzyme is effective in mitigating the effects of 8 g wheat protein ingestion in patients with celiac disease

Before and after 2-week intake period

Patients will consume 8 g wheat protein daily with AN-PEP enzyme for 14 d. After a 14-d washout period, patients who are negative for coeliac disease symptoms during the 1st period will randomly receive 8 g wheat protein daily with AN-PEP enzyme or placebo for another 14 d.