AN-PEP on Gluten Exposure in Celiacs

NCT04788797 | Completed Phase 4 FDA Drug

• 1 other identifier: DrUdaondo
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Celiac Disease

Keywords

celiac disease; endopeptidases; gliadin immunogenic peptides

Outcome Measures

Primary Outcomes (5)

• Frequency of GIP excretion in stool

  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

  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

  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

  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

  To determine weekly concentration of GIP excretion in urine (ng/mL) for both patients randomized to AN-PEP or placebo.

  4 weeks

Secondary Outcomes (4)

• Clinical effect of AN-PEP vs placebo

  4 weeks

• Differences in quality of life scores

  4 weeks

• Major symptoms

  4 weeks

• Biochemical effect of AN-PEP vs. placebo

  4 weeks

Study Arms (2)

Prolyl Endopeptidase

ACTIVE COMPARATOR

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

Drug: Prolyl Endopeptidase

Placebo

PLACEBO COMPARATOR

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

Interventions

Prolyl Endopeptidase DRUG

Two capsules three times a day.

Also known as: GliadinX

Prolyl Endopeptidase

Placebo OTHER

Two capsules three times a day

Placebo

Eligibility Criteria

• Age: 17 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,).

Sponsors & Collaborators

• Dr. C. Bonorino Udaondo Gastroenterology Hospital: lead

Study Sites (1)

Dr. C. Bonorino Udaondo Gastroenterology Hospital

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1602, Argentina

Location

Related Publications (8)

• Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, Martin FP, Cominetti O, Welsh C, Rieder A, Traynor J, Gregory C, De Palma G, Pigrau M, Ford AC, Macri J, Berger B, Bergonzelli G, Surette MG, Collins SM, Moayyedi P, Bercik P. Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome. Gastroenterology. 2017 Aug;153(2):448-459.e8. doi: 10.1053/j.gastro.2017.05.003. Epub 2017 May 5.

  PMID: 28483500 BACKGROUND

• Castellano E, Attanasio R, Gianotti L, Cesario F, Tassone F, Borretta G. Forearm DXA Increases the Rate of Patients With Asymptomatic Primary Hyperparathyroidism Meeting Surgical Criteria. J Clin Endocrinol Metab. 2016 Jul;101(7):2728-32. doi: 10.1210/jc.2016-1513. Epub 2016 Apr 12.

  PMID: 27070376 BACKGROUND

• Ricano-Ponce I, Gutierrez-Achury J, Costa AF, Deelen P, Kurilshikov A, Zorro MM, Platteel M, van der Graaf A; Consortium for the study of genetic associations of celiac disease in Latin-America; Sanna S, Daffra O, Zhernakova A, Fu J, Trynka G, Smecuol E, Niveloni SI, Bai JC, Kumar V, Wijmenga C. Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease. Eur J Hum Genet. 2020 Mar;28(3):313-323. doi: 10.1038/s41431-019-0520-4. Epub 2019 Oct 7.

  PMID: 31591516 BACKGROUND

• Pinto-Sanchez MI, Bai JC. Toward New Paradigms in the Follow Up of Adult Patients With Celiac Disease on a Gluten-Free Diet. Front Nutr. 2019 Oct 1;6:153. doi: 10.3389/fnut.2019.00153. eCollection 2019.

  PMID: 31632977 BACKGROUND

• Penny HA, Raju SA, Lau MS, Marks LJ, Baggus EM, Bai JC, Bassotti G, Bontkes HJ, Carroccio A, Danciu M, Derakhshan MH, Ensari A, Ganji A, Green PHR, Johnson MW, Ishaq S, Lebwohl B, Levene A, Maxim R, Mohaghegh Shalmani H, Rostami-Nejad M, Rowlands D, Spiridon IA, Srivastava A, Volta U, Villanacci V, Wild G, Cross SS, Rostami K, Sanders DS. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut. 2021 May;70(5):876-883. doi: 10.1136/gutjnl-2020-320913. Epub 2020 Nov 2.

  PMID: 33139268 BACKGROUND

• Seiler CL, Kiflen M, Stefanolo JP, Bai JC, Bercik P, Kelly CP, Verdu EF, Moayyedi P, Pinto-Sanchez MI. Probiotics for Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Am J Gastroenterol. 2020 Oct;115(10):1584-1595. doi: 10.14309/ajg.0000000000000749.

  PMID: 32740074 BACKGROUND

• Stefanolo JP, Talamo M, Dodds S, de la Paz Temprano M, Costa AF, Moreno ML, Pinto-Sanchez MI, Smecuol E, Vazquez H, Gonzalez A, Niveloni SI, Maurino E, Verdu EF, Bai JC. Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples. Clin Gastroenterol Hepatol. 2021 Mar;19(3):484-491.e1. doi: 10.1016/j.cgh.2020.03.038. Epub 2020 Mar 23.

  PMID: 32217152 BACKGROUND

• Smecuol E, Constante M, Temprano MP, Costa AF, Moreno ML, Pinto-Sanchez MI, Vazquez H, Stefanolo JP, Gonzalez AF, D'Adamo CR, Niveloni SI, Maurino E, Verdu EF, Bai JC. Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study. Benef Microbes. 2020 Oct 12;11(6):527-534. doi: 10.3920/BM2020.0016. Epub 2020 Oct 9.

  PMID: 33032471 BACKGROUND

MeSH Terms

Conditions

Celiac Disease

Interventions

Prolyl Oligopeptidases

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Edgardo G Smecuol

  Dr. C. Bonorino Udaondo Gastroenterology Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: March 9, 2021
• Study Start: March 17, 2021
• Primary Completion: July 30, 2022
• Study Completion: July 31, 2022
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)