Celiac DiseasePhase 2WHETMITNCT02472119
Wheat Flour Treatment With Microbial Transglutaminase and Lysine Ethyl Ester: New Frontiers in Celiac Disease Treatment.
A Phase 2 study testing rusks made of wheat flour enzymatically treated, rusks made of wheat flour not enzimatically modified and Gluten-free diet in people with Celiac Disease, run by University of Roma La Sapienza at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Celiac Disease
- What is being tested?
- rusks made of wheat flour enzymatically treated, rusks made of wheat flour not enzimatically modified and Gluten-free diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2015to Aug 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- inflammatory bowel diseases;
- tumors;
- infectious liver disease;
- renal impairment.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Sapienza University - Policlinico Umberto I
Rome, Italy, 00186
Antonio Picarelli, medicine, +390649978370, antonio.picarelli@uniroma1.it
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Celiac Disease
- Being tested
- rusks made of wheat flour enzymatically treated, rusks made of wheat flour not enzimatically modified, Gluten-free diet
- Keywords
- Celiac disease, Gluten-free diet, Wheat flour treatment, Microbial transglutaminase, Lysine Ethyl Ester, Celiac Disease Treatment
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rusks made of wheat flour enzymatically treatedDietary supplement
100 g of rusks obtained from commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months
rusks made of wheat flour not enzimatically modifiedDietary supplement
100 g of rusks obtained from commercial wheat flour NOT enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months
Gluten-free dietDietary supplement
gluten-free diet
| Study group | Role | What they receive |
|---|---|---|
| rusks made with treated flour | Experimental | Gluten-free diet adding rusks (100g / day) produced with commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester. Receives: Dietary Supplement: rusks made of wheat flour enzymatically treated; Dietary Supplement: Gluten-free diet |
| rusks made with not-treated flour | Active comparator | Gluten-free diet adding rusks (100g / day) produced with untreated wheat flour. Receives: Dietary Supplement: rusks made of wheat flour not enzimatically modified; Dietary Supplement: Gluten-free diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 30 days
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.
Measured: After 1 month
Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 60 days
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.
Measured: After 2 months
Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 90 days
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.
Measured: After 3 months
Change from baseline in IgA anti-endomysium antibodies (EMA) at 30 days
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''.
Measured: After 1 month
Change from baseline in IgA anti-endomysium antibodies (EMA) at 60 days
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''.
Measured: After 2 months
Change from baseline in IgA anti-endomysium antibodies (EMA) at 90 days
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''.
Measured: After 3 months
Pathologic variations in histologic analysis from baseline
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.
Measured: After 3 months, or in case of serum anti-tTG IgA/EMA IgA positive results
Secondary outcomes (16)
Presence of bloating at baseline
Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: At baseline
Presence of abdominal pain at baseline
Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: At baseline
Presence of diarrhea at baseline
Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: At baseline
Presence of asthenia at baseline
Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: At baseline
Variation of bloating from baseline at 30 days
Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 1 month
Variation of abdominal pain from baseline at 30 days
Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 1 month
Variation of diarrhea from baseline at 30 days
Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 1 month
Variation of asthenia from baseline at 30 days
Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 1 month
Variation of bloating from baseline at 60 days
Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 2 months
Variation of abdominal pain from baseline at 60 days
Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 2 months
Variation of diarrhea from baseline at 60 days
Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 2 months
Variation of asthenia from baseline at 60 days
Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 2 months
Variation of bloating from baseline at 90 days
Evaluation of bloating intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 3 months
Variation of abdominal pain from baseline at 90 days
Evaluation of abdominal pain intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 3 months
Variation of diarrhea from baseline at 90 days
Evaluation of diarrhea intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 3 months
Variation of asthenia from baseline at 90 days
Evaluation of asthenia intensity is reported according to the Visual Analog or Analogue Scale (VAS), with a range of 0-10.
Measured: After 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionAug 2015 (estimated)
- Study completionAug 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Celiac DiseaseStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antonio Picarelli, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472119
- Sponsor's protocol ID
- 672/10 Rif. 1907 / 22.07.2010
- Acronym
- WHETMIT
- Status last verified
- Jun 2015
- First submitted
- 3 Jun 2015
- Last updated
- 15 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Branski D, Fasano A, Troncone R. Latest developments in the pathogenesis and treatment of celiac disease. J Pediatr. 2006 Sep;149(3):295-300. doi: 10.1016/j.jpeds.2006.06.003. No abstract available.
PubMed 16939736Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology. 1998 Sep;115(3):551-63. doi: 10.1016/s0016-5085(98)70134-9.
PubMed 9721152Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Noren O, Roepstorff P, Lundin KE, Sjostrom H, Sollid LM. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med. 1998 Jun;4(6):713-7. doi: 10.1038/nm0698-713.
PubMed 9623982Gianfrani C, Siciliano RA, Facchiano AM, Camarca A, Mazzeo MF, Costantini S, Salvati VM, Maurano F, Mazzarella G, Iaquinto G, Bergamo P, Rossi M. Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology. 2007 Sep;133(3):780-9. doi: 10.1053/j.gastro.2007.06.023. Epub 2007 Jun 20.
PubMed 17678925Yokoyama K, Nio N, Kikuchi Y. Properties and applications of microbial transglutaminase. Appl Microbiol Biotechnol. 2004 May;64(4):447-54. doi: 10.1007/s00253-003-1539-5. Epub 2004 Jan 22.
PubMed 14740191Fink ML, Chung SI, Folk JE. gamma-Glutamylamine cyclotransferase: specificity toward epsilon-(L-gamma-glutamyl)-L-lysine and related compounds. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4564-8. doi: 10.1073/pnas.77.8.4564.
PubMed 6107907Catassi C, Fabiani E, Iacono G, D'Agate C, Francavilla R, Biagi F, Volta U, Accomando S, Picarelli A, De Vitis I, Pianelli G, Gesuita R, Carle F, Mandolesi A, Bearzi I, Fasano A. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr. 2007 Jan;85(1):160-6. doi: 10.1093/ajcn/85.1.160.
PubMed 17209192Picarelli A, Di Tola M, Sabbatella L, Anania MC, Calabro A, Renzi D, Bai JC, Sugai E, Carroccio A, Di Prima L, Bardella MT, Barisani D, Ribes-Koninckx C, Aliaga ED, Gasparin M, Bravi E; Multicentre Organ Culture System Study Group. Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: a multicentre study. Scand J Gastroenterol. 2006 Feb;41(2):186-90. doi: 10.1080/00365520510024151.
PubMed 16509042Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet. 1996 Oct 19;348(9034):1065-7. doi: 10.1016/S0140-6736(96)03060-7.
PubMed 8874458Marino M, Casale R, Borghini R, Di Nardi S, Donato G, Angeloni A, Moscaritolo S, Grasso L, Mazzarella G, Di Tola M, Rossi M, Picarelli A. The effects of modified versus unmodified wheat gluten administration in patients with celiac disease. Int Immunopharmacol. 2017 Jun;47:1-8. doi: 10.1016/j.intimp.2017.03.012. Epub 2017 Mar 23.
PubMed 28343108
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02472119
- Acronym / sponsor ID
- WHETMIT / 672/10 Rif. 1907 / 22.07.2010
- Conditions
- Celiac Disease
- Keywords
- Celiac disease, Gluten-free diet, Wheat flour treatment, Microbial transglutaminase, Lysine Ethyl Ester, Celiac Disease Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Aug 2015 (estimated)
- Study completion
- Aug 2015 (estimated)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rusks made with treated flour | Experimental | Dietary Supplement: rusks made of wheat flour enzymatically treated, Dietary Supplement: Gluten-free dietGluten-free diet adding rusks (100g / day) produced with commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester. |
| rusks made with not-treated flour | Active comparator | Dietary Supplement: rusks made of wheat flour not enzimatically modified, Dietary Supplement: Gluten-free dietGluten-free diet adding rusks (100g / day) produced with untreated wheat flour. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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;
Key exclusion criteria (4 listed)
- inflammatory bowel diseases;
- tumors;
- infectious liver disease;
- renal impairment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rusks made of wheat flour enzymatically treated100 g of rusks obtained from commercial wheat flour enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months | Dietary supplement | rusks made with treated flour |
| rusks made of wheat flour not enzimatically modified100 g of rusks obtained from commercial wheat flour NOT enzymatically treated with mTGasi and lysine ethyl ester, every day for 3 months | Dietary supplement | rusks made with not-treated flour |
| Gluten-free dietgluten-free diet | Dietary supplement | rusks made with not-treated flour, rusks made with treated flour |
Primary outcome
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.
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.
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.
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''.
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''.
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''.
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.
16 secondary outcomes
Presence of bloating at baseline
Time frame: At baseline
Presence of abdominal pain at baseline
Time frame: At baseline
Presence of diarrhea at baseline
Time frame: At baseline
Presence of asthenia at baseline
Time frame: At baseline
Variation of bloating from baseline at 30 days
Time frame: After 1 month
Variation of abdominal pain from baseline at 30 days
Time frame: After 1 month
Variation of diarrhea from baseline at 30 days
Time frame: After 1 month
Variation of asthenia from baseline at 30 days
Time frame: After 1 month
Variation of bloating from baseline at 60 days
Time frame: After 2 months
Variation of abdominal pain from baseline at 60 days
Time frame: After 2 months
Variation of diarrhea from baseline at 60 days
Time frame: After 2 months
Variation of asthenia from baseline at 60 days
Time frame: After 2 months
Variation of bloating from baseline at 90 days
Time frame: After 3 months
Variation of abdominal pain from baseline at 90 days
Time frame: After 3 months
Variation of diarrhea from baseline at 90 days
Time frame: After 3 months
Variation of asthenia from baseline at 90 days
Time frame: After 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2015.
- Background: PubMed 16939736Branski D, Fasano A, Troncone R. Latest developments in the pathogenesis and treatment of celiac disease. J Pediatr. 2006 Sep;149(3):295-300. doi: 10.1016/j.jpeds.2006.06.003. No abstract available.
- Background: PubMed 9721152Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology. 1998 Sep;115(3):551-63. doi: 10.1016/s0016-5085(98)70134-9.
- Background: PubMed 9623982Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Noren O, Roepstorff P, Lundin KE, Sjostrom H, Sollid LM. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med. 1998 Jun;4(6):713-7. doi: 10.1038/nm0698-713.
- Background: PubMed 17678925Gianfrani C, Siciliano RA, Facchiano AM, Camarca A, Mazzeo MF, Costantini S, Salvati VM, Maurano F, Mazzarella G, Iaquinto G, Bergamo P, Rossi M. Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology. 2007 Sep;133(3):780-9. doi: 10.1053/j.gastro.2007.06.023. Epub 2007 Jun 20.
- Background: PubMed 14740191Yokoyama K, Nio N, Kikuchi Y. Properties and applications of microbial transglutaminase. Appl Microbiol Biotechnol. 2004 May;64(4):447-54. doi: 10.1007/s00253-003-1539-5. Epub 2004 Jan 22.
- Background: PubMed 6107907Fink ML, Chung SI, Folk JE. gamma-Glutamylamine cyclotransferase: specificity toward epsilon-(L-gamma-glutamyl)-L-lysine and related compounds. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4564-8. doi: 10.1073/pnas.77.8.4564.
- Background: PubMed 17209192Catassi C, Fabiani E, Iacono G, D'Agate C, Francavilla R, Biagi F, Volta U, Accomando S, Picarelli A, De Vitis I, Pianelli G, Gesuita R, Carle F, Mandolesi A, Bearzi I, Fasano A. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr. 2007 Jan;85(1):160-6. doi: 10.1093/ajcn/85.1.160.
- Background: PubMed 16509042Picarelli A, Di Tola M, Sabbatella L, Anania MC, Calabro A, Renzi D, Bai JC, Sugai E, Carroccio A, Di Prima L, Bardella MT, Barisani D, Ribes-Koninckx C, Aliaga ED, Gasparin M, Bravi E; Multicentre Organ Culture System Study Group. Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: a multicentre study. Scand J Gastroenterol. 2006 Feb;41(2):186-90. doi: 10.1080/00365520510024151.
- Background: PubMed 8874458Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet. 1996 Oct 19;348(9034):1065-7. doi: 10.1016/S0140-6736(96)03060-7.
- Derived from this study: PubMed 28343108Marino M, Casale R, Borghini R, Di Nardi S, Donato G, Angeloni A, Moscaritolo S, Grasso L, Mazzarella G, Di Tola M, Rossi M, Picarelli A. The effects of modified versus unmodified wheat gluten administration in patients with celiac disease. Int Immunopharmacol. 2017 Jun;47:1-8. doi: 10.1016/j.intimp.2017.03.012. Epub 2017 Mar 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rusks made of wheat flour enzymatically treated, rusks made of wheat flour not enzimatically modified and Gluten-free diet in people with Celiac Disease, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Picarelli, medicine (+39 06 49978370, antonio.picarelli@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in IgA anti-tissue transglutaminase (anti-tTG) antibodies at 30 days (time frame: After 1 month). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02472119, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2015.