AN-PEP on Gluten Exposure in Celiacs

Dr. C. Bonorino Udaondo Gastroenterology Hospital

Status and phase: Completed; Phase 4

Conditions: Celiac Disease

Treatments: Drug: Prolyl Endopeptidase; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04788797

DrUdaondo

Details and patient eligibility

About

The AN-PEP, an Aspergillus niger derived endopeptidase, has been developed aiming to produce a complete luminal detoxification of gluten. If AN-PEP is able to produce a complete luminal digestion of gluten in the context of the real life of celiac disease (CeD) patients is unknown. Hypothetically, AN-PEP effect could be detected by the reduction in the excretion of GIP in stool and urine.

The objective of this study is to establish the effect of the daily administration of AN-PEP compared to placebo on GIP excretion in an interventional, prospective, randomized, comparative, double-blind study in conditions mimicking the real-life of CeD treated patients. The study consists in a four-week GFD stabilization period followed by a four-week study period with patients randomized to receive active AN-PEP or placebo in a blindly manner.

Full description

Background: The strict gluten-free diet (GFD) is the only accepted treatment for celiac disease (CeD). However, performing a strict diet is still a non solved problem affecting the future of patients. In a real-life study it was recently shown that 89% of treated CeD patients performing a strict diet have contact with dietary gluten at least one week per 4 weeks of testing and averaging 3 weeks per month. Furthermore, 40% of patients excreted gliadin immunogenic peptides (GIP) (surrogated markers of gluten exposure) in the range for immunological activation and intestinal mucosal damage. Endopeptidases to produce a complete intraluminal proteolysis of gluten avoiding antigenic stimulation were produced to avoid damage of continuous gluten exposure. AN-PEP is an Aspergillus niger derived endopeptidase has been produced aiming to luminal detoxification of gluten have been explored for its clinical effect. However, whether AN-PEP is able to completely destroy gluten in the context of the real life of CeD patients is still unknown. Hypothesis: The investigators estimate that AN-PEP is an effective therapy for proteolysis for gluten exposure in the real-life of CeD patients and that the effect could be detected by the reduction in the excretion of GIP in stool and urine based on a clinical research model that we developed. AIMS: to establish the effect of daily administration of AN-PEP compared to placebo in terms of: (1) frequency of GIP excretion in stool and urine episodes in 4 weeks; (2) concentration of GIP excretion for both arms; and (3) differences in proportion of patients excreting GIP above the threshold for mucosal damage (>2 µg/g of GIP in stool or >12 ng/mL in urine). Study design: Interventional, prospective, randomized, comparative, double-blind study. Components: 1- four-week GFD stabilization period; 2-Randomization. 3- four4-week study period: Patients blinded-receive active AN-PEP (GliadinX®) at a dose of 2 capsules/breakfast, lunch and dinner (study arm), or 2 capsules at same time points of placebo (specially designed and prepared for the study) (Placebo arm).

Enrollment: 40 patients

Sex: All

Ages: 17 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Over 18 years
• Diagnosis of celiac disease
• Completion of Gluten-free Diet for at least two years without evidence of voluntary violations.
• Patients who do not report symptoms of constipation or illnesses or medications (cathartics, antidiarrheals, etc.) that alter the bowel movement rhythm (accepted rhythm: between 2 times / day to 1 every other day) and diuresis (diuretics). Proton-pump inhibitor.
• Signature of the informed consent

Exclusion criteria

• Patients not interested or unable to collaborate with the questionnaires and collection of fecal matter.
• Place of residence of the participant more than 4 hours from the hospital, which interferes with the viability of the sample.
• Complicated CD (refractory CD type II, ulcerative jejunoileitis, lymphoma).
• Concomitant pathologies that are decompensated or untreated at study entry (type I or II diabetes mellitus; hyperthyroidism; hypothyroidism; kidney failure,).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

40 participants in 2 patient groups, including a placebo group

Prolyl Endopeptidase

Active Comparator group

Description:

Patients blinded-receive active AN-PEP at a dose of 2 capsules/breakfast, lunch and dinner during 8 weeks (study arm)

Treatment:

Drug: Prolyl Endopeptidase

Placebo

Placebo Comparator group

Description:

Patients blinded-receive 2 capsules of a placebo (specially designed and prepared for the study) at breakfast, lunch and dinner during 8 weeks (Placebo arm).

Treatment:

Other: Placebo