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Trial record 27 of 193 for:    CELIAC DISEASE

Wheat Flour Treatment With Microbial Transglutaminase and Lysine Ethyl Ester: New Frontiers in Celiac Disease Treatment. (WHETMIT)

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ClinicalTrials.gov Identifier: NCT02472119
Recruitment Status : Unknown
Verified June 2015 by Antonio Picarelli, University of Roma La Sapienza.
Recruitment status was:  Recruiting
First Posted : June 15, 2015
Last Update Posted : June 15, 2015
Sponsor:
Information provided by (Responsible Party):
Antonio Picarelli, University of Roma La Sapienza

Brief Summary:

Celiac disease is one of the most common forms of food intolerance (prevalence 1/200). The disease occurs in genetically predisposed individuals after ingestion of foods containing gluten. Celiac patients can suffer from severe malabsorption syndrome, mainly characterized by diarrhea and weight loss. The only therapeutic approach currently recognized is a life-long gluten-free diet.

Specific regions of gluten molecule become recognizable by lymphocytes and activate them, due to changes made by tissue transglutaminase. These changes consist in the conversion of specific residues of glutamine into glutamic acid. The consequence is an increased binding affinity between gluten and histocompatibility molecule (HLA-DQ2), localized on the surface of the "antigen presenting cells" (APC); the exposure of the fragments of modified gluten on the surface of APC is a phenomenon that eventually activates T lymphocytes.

Recent studies on modified gluten confirmed the hypothesis that it is possible to block the presentation of gluten to lymphocytes by means of lysine ethyl ester binding exclusively to those gluten regions responsible for lymphocyte activation.

The enzymatic treatment is performed directly on flour instead of extracted gluten, maintaining the same anti-inflammatory effectiveness.

The procedure uses a food-grade enzyme, the microbial transglutaminase (mTGasi) isolated from Streptoverticillium mobarensis, able to catalyze the formation of intermolecular "cross-links" that modify the functional properties of the products.

Objective of the study is to validate the ability of the enzyme treatment of wheat flour with mTGasi and lysine ethyl ester to block the toxic effect of gluten in celiac patients.


Condition or disease Intervention/treatment Phase
Celiac Disease Dietary Supplement: rusks made of wheat flour enzymatically treated Dietary Supplement: rusks made of wheat flour not enzimatically modified Dietary Supplement: Gluten-free diet Phase 2

Detailed Description:

Celiac disease is one of the most common forms of food intolerance (prevalence 1/200). The disease occurs in genetically predisposed individuals after ingestion of foods containing wheat gluten and similar proteins found in other common cereals such as barley and rye. Celiac patients can suffer from severe malabsorption syndrome, mainly characterized by diarrhea, weight loss and growth retardation. The only therapeutic approach currently recognized is a life-long gluten-free diet.

Specific regions of gluten molecule become recognizable by lymphocytes and activate them, due to changes made by tissue transglutaminase. These changes consist in the conversion of specific residues of glutamine (Q) into glutamic acid (E). The consequence is an increased binding affinity between gluten and histocompatibility molecule (HLA-DQ2), localized on the surface of the "antigen presenting cells" (APC); the exposure of the fragments of modified gluten on the surface of APC is a phenomenon that eventually activates T lymphocytes.

Recent studies on modified gluten confirmed the hypothesis that it is possible to block the presentation of gluten to lymphocytes by means of lysine ethyl ester binding exclusively to those gluten regions responsible for lymphocyte activation.

Specifically, it is possible to perform the enzymatic treatment directly on flour instead of extracted gluten, maintaining the same anti-inflammatory effectiveness. The final procedure consists in dissolving the flour in water in the presence of appropriate concentrations of enzyme and lysine ethyl ester, maintaining the suspension in constant motion for two hours at room temperature.

The procedure uses a food-grade enzyme, the microbial transglutaminase (mTGasi) isolated from Streptoverticillium mobarensis, already used for the preparation of food. The mTgasi is able to catalyze the formation of intermolecular "cross-links" modifying the functional properties of the products through the aggregation and polymerization of proteins. The peculiar method identified by our laboratory reduces the possibility of cross-links between proteins: consequently, minimal changes involve the gluten structure and, consequently, the visco-elastic properties of the dough.

Objective of the study is to validate the ability of the enzyme treatment of wheat flour with mTGasi and lysine ethyl ester to block the toxic effect of gluten in celiac patients.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Wheat Flour Subjected to Microbial Transglutaminase Enzymatic Treatment in the Presence of Lysine Ethyl Ester for Alimentary Use in the Treatment of Celiac Disease.
Study Start Date : June 2015
Estimated Primary Completion Date : August 2015
Estimated Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Experimental: rusks made with treated flour
Gluten-free diet adding rusks (100g / day) produced with commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester.
Dietary Supplement: rusks made of wheat flour enzymatically treated
100 g of rusks obtained from commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months

Dietary Supplement: Gluten-free diet
gluten-free diet

Active Comparator: rusks made with not-treated flour
Gluten-free diet adding rusks (100g / day) produced with untreated wheat flour.
Dietary Supplement: rusks made of wheat flour not enzimatically modified
100 g of rusks obtained from commercial wheat flour NOT enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months

Dietary Supplement: Gluten-free diet
gluten-free diet




Primary Outcome Measures :
  1. Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 30 days [ Time Frame: After 1 month ]
    Proof of any positivization of specific serological antibodies for celiac disease. Results quantified by an ELISA reader at 450 nm (A450nm) is expressed in U/mL and the antibody level 10 U/mL was used as a cutoff value to identify anti-tTG positive results.

  2. Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 60 days [ Time Frame: After 2 months ]
    Proof of any positivization of specific serological antibodies for celiac disease. Results quantified by an ELISA reader at 450 nm (A450nm) is expressed in U/mL and the antibody level 10 U/mL was used as a cutoff value to identify anti-tTG positive results.

  3. Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 90 days [ Time Frame: After 3 months ]
    Proof of any positivization of specific serological antibodies for celiac disease. Results quantified by an ELISA reader at 450 nm (A450nm) is expressed in U/mL and the antibody level 10 U/mL was used as a cutoff value to identify anti-tTG positive results.

  4. Change from baseline in IgA anti-endomysium antibodies (EMA) at 30 days [ Time Frame: After 1 month ]
    Test used to confirm serological activation of celiac disease. IgA EMA were searched in sera diluted 1:5 by indirect immunofluorescence analysis on cryostat sections of monkey esophagus. The results are expressed as ''positive/negative''.

  5. Change from baseline in IgA anti-endomysium antibodies (EMA) at 60 days [ Time Frame: After 2 months ]
    Test used to confirm serological activation of celiac disease. IgA EMA were searched in sera diluted 1:5 by indirect immunofluorescence analysis on cryostat sections of monkey esophagus. The results are expressed as ''positive/negative''.

  6. Change from baseline in IgA anti-endomysium antibodies (EMA) at 90 days [ Time Frame: After 3 months ]
    Test used to confirm serological activation of celiac disease. IgA EMA were searched in sera diluted 1:5 by indirect immunofluorescence analysis on cryostat sections of monkey esophagus. The results are expressed as ''positive/negative''.

  7. Pathologic variations in histologic analysis from baseline [ Time Frame: After 3 months, or in case of serum anti-tTG IgA/EMA IgA positive results ]
    Proof of duodenal mucosa histological alterations induced by celiac disease, consisting in altered (<3:1) villous height/crypt depth ratio and increased (>25) intraepithelial lymphocytes per 100 intestinal epithelial cells, according to Marsh-Oberhuber classification.


Secondary Outcome Measures :
  1. Presence of bloating at baseline [ Time Frame: At baseline ]
    Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  2. Presence of abdominal pain at baseline [ Time Frame: At baseline ]
    Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  3. Presence of diarrhea at baseline [ Time Frame: At baseline ]
    Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  4. Presence of asthenia at baseline [ Time Frame: At baseline ]
    Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  5. Variation of bloating from baseline at 30 days [ Time Frame: After 1 month ]
    Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  6. Variation of abdominal pain from baseline at 30 days [ Time Frame: After 1 month ]
    Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  7. Variation of diarrhea from baseline at 30 days [ Time Frame: After 1 month ]
    Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  8. Variation of asthenia from baseline at 30 days [ Time Frame: After 1 month ]
    Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  9. Variation of bloating from baseline at 60 days [ Time Frame: After 2 months ]
    Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  10. Variation of abdominal pain from baseline at 60 days [ Time Frame: After 2 months ]
    Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  11. Variation of diarrhea from baseline at 60 days [ Time Frame: After 2 months ]
    Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  12. Variation of asthenia from baseline at 60 days [ Time Frame: After 2 months ]
    Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  13. Variation of bloating from baseline at 90 days [ Time Frame: After 3 months ]
    Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  14. Variation of abdominal pain from baseline at 90 days [ Time Frame: After 3 months ]
    Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  15. Variation of diarrhea from baseline at 90 days [ Time Frame: After 3 months ]
    Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.

  16. Variation of asthenia from baseline at 90 days [ Time Frame: After 3 months ]
    Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

INCLUSION CRITERIA

  • diagnosis of celiac disease according to ESPGHAN criteria: class III according to Marsh-Oberhuber classification, clear response to gluten-free diet, serological antiendomysium and antitransglutaminase antibodies positive results before GFD;
  • HLA DQ2-DQ8 positive results;
  • gluten-free diet from at least one year;
  • negative serology from at least 1 year;

EXCLUSION CRITERIA

  • inflammatory bowel diseases;
  • tumors;
  • infectious liver disease;
  • renal impairment.

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): NCT02472119


Contacts
Contact: Antonio Picarelli, medicine +39 06 49978370 antonio.picarelli@uniroma1.it

Locations
Italy
Sapienza University - Policlinico Umberto I Recruiting
Rome, Italy, 00186
Contact: Antonio Picarelli, medicine    +390649978370    antonio.picarelli@uniroma1.it   
Sponsors and Collaborators
University of Roma La Sapienza

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Antonio Picarelli, Medical Doctor, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT02472119     History of Changes
Other Study ID Numbers: 672/10 Rif. 1907 / 22.07.2010
First Posted: June 15, 2015    Key Record Dates
Last Update Posted: June 15, 2015
Last Verified: June 2015

Keywords provided by Antonio Picarelli, University of Roma La Sapienza:
Celiac disease
Gluten-free diet
Wheat flour treatment
Microbial transglutaminase
Lysine Ethyl Ester
Celiac Disease Treatment

Additional relevant MeSH terms:
Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases