AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as co...AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable serum antibodies,while 14 patients were considered histologically stable on gluten with AN-PEP.Also after the efficacy phase,no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP.Furthermore,IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo.In the seven patients receiving AN-PEP,one patient showed increased and one showed decreased IgA-tTG deposits.CONCLUSION:AN-PEP appears to be well tolerated.However,the primary endpoint was not met due to lack of clinical deterioration upon placebo,impeding an effect of AN-PEP.展开更多
At present,treatment for celiac disease includes a strict gluten-free diet.Compliance,however,is difficult and gluten-free food products are costly,and,sometimes very inconvenient.A number of potential alternative mea...At present,treatment for celiac disease includes a strict gluten-free diet.Compliance,however,is difficult and gluten-free food products are costly,and,sometimes very inconvenient.A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy.In the past,non-dietary forms of treatment were used(e.g.,corticosteroids) by some clinicians,often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet.Some of new and novel non-dietary measures have already advanced to a clinical trial phase.There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment.In particular,precise monitoring of the response to these agents will become critical.Symptom or laboratory improvement may be important,but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present.Therapeutic trials will be made more difficult because there is already an effective treatment regimen.展开更多
文摘AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable serum antibodies,while 14 patients were considered histologically stable on gluten with AN-PEP.Also after the efficacy phase,no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP.Furthermore,IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo.In the seven patients receiving AN-PEP,one patient showed increased and one showed decreased IgA-tTG deposits.CONCLUSION:AN-PEP appears to be well tolerated.However,the primary endpoint was not met due to lack of clinical deterioration upon placebo,impeding an effect of AN-PEP.
文摘At present,treatment for celiac disease includes a strict gluten-free diet.Compliance,however,is difficult and gluten-free food products are costly,and,sometimes very inconvenient.A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy.In the past,non-dietary forms of treatment were used(e.g.,corticosteroids) by some clinicians,often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet.Some of new and novel non-dietary measures have already advanced to a clinical trial phase.There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment.In particular,precise monitoring of the response to these agents will become critical.Symptom or laboratory improvement may be important,but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present.Therapeutic trials will be made more difficult because there is already an effective treatment regimen.
