AN-PEP on Gluten Exposure in Celiacs
Condition: Celiac Disease
MeSH terms: Celiac Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed 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).
    

Intervention name(s): Prolyl Endopeptidase; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Two capsules three times a day.; Two capsules three times a day
Other intervention name(s): GliadinX
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: celiac disease; endopeptidases; gliadin immunogenic peptides