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AN-PEP on Gluten Exposure in Celiacs

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ClinicalTrials.gov Identifier: NCT04788797
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Edgardo Smecuol, Dr. C. Bonorino Udaondo Gastroenterology Hospital

Brief 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.


Condition or disease Intervention/treatment Phase
Celiac Disease Drug: Prolyl Endopeptidase Other: Placebo Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 17, 2021
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

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 Name: 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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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. 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

  5. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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,).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04788797


Contacts
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Contact: Edgardo G Smecuol, MD +541144911975 esmecuol@intramed.net

Locations
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Argentina
Dr. C. Bonorino Udaondo Gastroenterology Hospital Recruiting
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1602
Contact: Edgardo G Smecuol, MD    +5491144911975    esmecuol@intramed.net   
Sponsors and Collaborators
Dr. C. Bonorino Udaondo Gastroenterology Hospital
Investigators
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Study Chair: Edgardo G Smecuol Dr. C. Bonorino Udaondo Gastroenterology Hospital
Publications:

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Responsible Party: Edgardo Smecuol, Principal Investigator, Dr. C. Bonorino Udaondo Gastroenterology Hospital
ClinicalTrials.gov Identifier: NCT04788797    
Other Study ID Numbers: DrUdaondo
First Posted: March 9, 2021    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Edgardo Smecuol, Dr. C. Bonorino Udaondo Gastroenterology Hospital:
celiac disease
endopeptidases
gliadin immunogenic peptides
Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases