AN-PEP on Gluten Exposure in Celiacs

February 22, 2023 updated by: Edgardo Smecuol, Dr. C. Bonorino Udaondo Gastroenterology Hospital

Effect of the Endopeptidase AN-PEP on Gluten Exposure in Real Life in Celiac Disease Patients Treated With a Long-term Gluten-free Diet. Exploratory, Interventional, Prospective, Controlled and Double Blind Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1602
        • Dr. C. Bonorino Udaondo Gastroenterology Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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,).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Prolyl Endopeptidase
Patients blinded-receive active AN-PEP at a dose of 2 capsules/breakfast, lunch and dinner during 8 weeks (study arm)
Drug: Prolyl Endopeptidase
Two capsules three times a day.
Other Names:
  • GliadinX
Placebo Comparator: Placebo
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).
Other: Placebo
Two capsules three times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of GIP excretion in stool
Time Frame: 4 weeks
To establish the effect of daily administration of AN-PEP compared to placebo in terms of frequency of GIP excretion in stool episodes in 4 weeks.
4 weeks
Weekly concentration of GIP excretion in stool
Time Frame: 4 weeks
To determine weekly concentration of GIP excretion in stool (µg/g of GIP) for both patients randomized to AN-PEP or placebo.
4 weeks
Proportion of patients excreting GIP
Time Frame: 4 weeks
To establish the proportion of patients excreting GIP above the theoretical threshold for mucosal damage (>1.6 µg/g of GIP in stool or >12 ng/mL in urine)
4 weeks
Frequency of GIP excretion in urine
Time Frame: 4 weeks
To establish the effect of daily administration of AN-PEP compared to placebo in terms of frequency of GIP excretion in urine epidodes in 4 weeks
4 weeks
Weekly concentration of GIP excretion in urine
Time Frame: 4 weeks
To determine weekly concentration of GIP excretion in urine (ng/mL) for both patients randomized to AN-PEP or placebo.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical effect of AN-PEP vs placebo
Time Frame: 4 weeks
2.1- To establish differences in the clinical effect of AN-PEP vs. placebo in symptomatic celiac patients in terms of the Celiac Clinical Score comparing baseline scores vs. those from the end of the study period. Celiac Clinical Score is made up of sixteen items, 11 of which evaluate "specific symptoms" and 5 evaluate "general health". Each question is answered on a Likert scale from 1 to 5. Overall symptom scores were calculated through simple addition, with higher scores denoting more severe symptoms. Scores of 45 or higher are associated with a relatively poor quality of life and worse GFD adherence. Score less than 45 are associated with better quality of life and gluten adherence
4 weeks
Differences in quality of life scores
Time Frame: 4 weeks
To determine differences in quality of life according to the Short Form 36 questionnaire in the study period in symptomatic and asymptomatic patients. To score this questionnaire scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.
4 weeks
Major symptoms
Time Frame: 4 weeks
To explore changes in the daily report of major symptoms (abdominal pain, discomfort, borborygmi, distension, diarrhea) (Likert scale of seven points) in symptomatic patients by using a daily report in a telephonic APP.
4 weeks
Biochemical effect of AN-PEP vs. placebo
Time Frame: 4 weeks
to evaluate changes that occur during the study period in concentrations of CD-specific antibodies (IgA TG2 and DGP antibodies -AU/mL-) comparing consumption of AN-PEP vs. placebo.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr. C. Bonorino Udaondo Gastroenterology Hospital

Investigators

  • Study Chair: Edgardo G Smecuol, Dr. C. Bonorino Udaondo Gastroenterology Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2021

Primary Completion (Actual)

July 30, 2022

Study Completion (Actual)

July 31, 2022

Study Registration Dates

First Submitted

February 3, 2021

First Submitted That Met QC Criteria

March 5, 2021

First Posted (Actual)

March 9, 2021

Study Record Updates

Last Update Posted (Actual)

February 24, 2023

Last Update Submitted That Met QC Criteria

February 22, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DrUdaondo

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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