Exocrine Pancreatic Insufficiency After Acute Pancreatitis and Pancreatic Enzyme Replacement Therapy
NCT ID: NCT05480241
Last Updated: 2022-07-29
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
UNKNOWN
Clinical Phase
NA
Total Enrollment
84 participants
Study Classification
INTERVENTIONAL
Study Start Date
2022-05-01
Study Completion Date
2024-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Acute pancreatitis represents an acute inflammatory process of the pancreas, which undergoes local and systemic complications, associated with non-negligible morbidity and mortality, and significant economic and quality of life impact. Even after the recovery phase, the development and persistence of sequelae from the inflammatory/necrotic process, including exocrine and endocrine pancreatic insufficiencies, are frequent. Although well documented as consequence of other pancreatic conditions, exocrine pancreatic insufficiency (EPI) after acute pancreatitis is poorly studied and probably underdiagnosed. The prevalence, diagnosis, independent risk factors and therapeutic approaches for EPI after acute pancreatitis need further investigation. Recent evidence suggests the involvement of the pancreas-intestinal axis and immunological dysfunction in several pancreatic pathologies, although their role in the development of EPI after acute pancreatitis is still scarce. Pancreatic enzyme replacement therapy (PERT) is the only treatment currently available in EPI, but the timing for start and duration of this therapy in acute pancreatitis remain to be established. This study have the following objectives: to determine the prevalence, clinical, analytical and nutritional biomarkers and duration of EPI after acute pancreatitis, as well as changes in gut microbiota and immunologic response, and quality of life in EPI and response to PERT after acute pancreatitis; and to determine the prevalence and biomarkers associated with endocrine pancreatic insufficiency following acute pancreatitis and the presence of gut dysbiosis and immunologic changes in acute pancreatitis according to its severity.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Introduction: Acute pancreatitis represents an acute inflammatory process of the pancreas, which undergoes local and systemic complications, associated with non-negligible morbidity and mortality, and significant economic and quality of life impact. Even after the recovery phase, the development and persistence of sequelae from the inflammatory/necrotic process, including exocrine and endocrine pancreatic insufficiencies, are frequent. Although well documented as consequence of other pancreatic conditions, exocrine pancreatic insufficiency (EPI) after acute pancreatitis is poorly studied and probably underdiagnosed. The prevalence, diagnosis, independent risk factors and therapeutic approaches for EPI after acute pancreatitis need further investigation. Recent evidence suggests the involvement of the pancreas-intestinal axis and immunological dysfunction in several pancreatic pathologies, although their role in the development of EPI after acute pancreatitis is still scarce. Pancreatic enzyme replacement therapy (PERT) is the only treatment currently available in EPI, but the timing for start and duration of this therapy in acute pancreatitis remain to be established.
Objectives: Primary objectives: To determine the prevalence, clinical, analytical and nutritional biomarkers and duration of EPI after acute pancreatitis, as well as changes in gut microbiota and immunologic response, and quality of life in EPI and response to PERT after acute pancreatitis. Secondary objectives: To determine the prevalence and biomarkers associated with endocrine pancreatic insufficiency following acute pancreatitis and the presence of gut dysbiosis and immunologic changes in acute pancreatitis according to its severity.
Methods: Prospective longitudinal study of total of patients consecutively admitted to the Gastroenterology Department of Coimbra Hospital and University Centre with acute pancreatitis diagnosis and double-blind randomized placebo-controlled clinical trial of PERT in patients developing EPI after acute pancreatitis. This study will be conducted in 4 Phases: Phase 1 - Recruitment of patients with acute pancreatitis and stratification of them according to the severity of acute pancreatitis and development of EPI (12-month followup), diagnosed by fecal elastase-1, 13C-labeled mixed triglyceride breath test assessing exocrine pancreatic function and comparison of them with 72-hour fecal fat quantification, as gold standard; Phase 2 - Double-blind randomized placebo-controlled trial in patients with EPI after acute pancreatitis for PERT with assessment of efficacy and safety of this therapy at 1 and 6 months post-randomization; Phase 3 - Evaluation of richness, diversity and uniformity of gut microbiota by DNA sequencing using the hypervariable region of the 16S ribosomal RNA gene as a taxonomic identification marker and assessment of quality of life using SF-36 and QLC-C30-V.3 scales (validated versions for the Portuguese population) in EPI patients after acute pancreatitis, and the impact of PERT on clinical course, gut dysbiosis and quality of life of patients (at the diagnosis of acute pancreatitis, EPI and after PERT); and Phase 4 - Analysis of immunological changes through the study of cell populations by flow cytometry (CD4+, CD8+, B-cell, T-cell, natural killer cells, cells ratio) and cytokines, chemokines and growth factors by xMAP/Luminex, at the diagnosis of acute pancreatitis, EPI and after PERT.
Expected results, impact and scientific outputs: Data on the prevalence of EPI after acute pancreatitis in its different forms of severity and the role of gut dysbiosis and immunologic changes remains unclear. It's expected that an adequate and timely diagnosis of this clinical condition will allow an early start of therapy with positive impact on clinical course, immunologic and gut homeostasis, survival and quality of life. With this study we expect to obtain a prevalence of EPI at admission of 25-62%, which should decrease during followup. Alcoholic etiology, severity of acute pancreatitis and the presence of pancreatic necrosis should be positively associated with the presence of EPI after acute pancreatitis. The prevalence of endocrine pancreatic insufficiency (pre-diabetes or diabetes mellitus) should be up to 40%. Nutritional deficits (single or multiple), breath test assessing exocrine pancreatic function and fecal elastase-1 are also expected to be positively associated with the development of EPI. It's expected that patients with acute pancreatitis developing EPI will have significant changes on gut microbiota and immunologic response, and PERT and/or gut microbiota modulating therapy, including prebiotics, probiotics, symbiotics and fecal microbiota transplantation, and probably targeted immunotherapies may have a beneficial impact on all patients or groups at risk, such as EPI, severe or necrotizing acute pancreatitis by reverting gut and immunologic dysbiosis, and improving quality of life.
Objectives: Primary objectives: To determine the prevalence, clinical, analytical and nutritional biomarkers and duration of EPI after acute pancreatitis, as well as changes in gut microbiota and immunologic response, and quality of life in EPI and response to PERT after acute pancreatitis. Secondary objectives: To determine the prevalence and biomarkers associated with endocrine pancreatic insufficiency following acute pancreatitis and the presence of gut dysbiosis and immunologic changes in acute pancreatitis according to its severity.
Methods: Prospective longitudinal study of total of patients consecutively admitted to the Gastroenterology Department of Coimbra Hospital and University Centre with acute pancreatitis diagnosis and double-blind randomized placebo-controlled clinical trial of PERT in patients developing EPI after acute pancreatitis. This study will be conducted in 4 Phases: Phase 1 - Recruitment of patients with acute pancreatitis and stratification of them according to the severity of acute pancreatitis and development of EPI (12-month followup), diagnosed by fecal elastase-1, 13C-labeled mixed triglyceride breath test assessing exocrine pancreatic function and comparison of them with 72-hour fecal fat quantification, as gold standard; Phase 2 - Double-blind randomized placebo-controlled trial in patients with EPI after acute pancreatitis for PERT with assessment of efficacy and safety of this therapy at 1 and 6 months post-randomization; Phase 3 - Evaluation of richness, diversity and uniformity of gut microbiota by DNA sequencing using the hypervariable region of the 16S ribosomal RNA gene as a taxonomic identification marker and assessment of quality of life using SF-36 and QLC-C30-V.3 scales (validated versions for the Portuguese population) in EPI patients after acute pancreatitis, and the impact of PERT on clinical course, gut dysbiosis and quality of life of patients (at the diagnosis of acute pancreatitis, EPI and after PERT); and Phase 4 - Analysis of immunological changes through the study of cell populations by flow cytometry (CD4+, CD8+, B-cell, T-cell, natural killer cells, cells ratio) and cytokines, chemokines and growth factors by xMAP/Luminex, at the diagnosis of acute pancreatitis, EPI and after PERT.
Expected results, impact and scientific outputs: Data on the prevalence of EPI after acute pancreatitis in its different forms of severity and the role of gut dysbiosis and immunologic changes remains unclear. It's expected that an adequate and timely diagnosis of this clinical condition will allow an early start of therapy with positive impact on clinical course, immunologic and gut homeostasis, survival and quality of life. With this study we expect to obtain a prevalence of EPI at admission of 25-62%, which should decrease during followup. Alcoholic etiology, severity of acute pancreatitis and the presence of pancreatic necrosis should be positively associated with the presence of EPI after acute pancreatitis. The prevalence of endocrine pancreatic insufficiency (pre-diabetes or diabetes mellitus) should be up to 40%. Nutritional deficits (single or multiple), breath test assessing exocrine pancreatic function and fecal elastase-1 are also expected to be positively associated with the development of EPI. It's expected that patients with acute pancreatitis developing EPI will have significant changes on gut microbiota and immunologic response, and PERT and/or gut microbiota modulating therapy, including prebiotics, probiotics, symbiotics and fecal microbiota transplantation, and probably targeted immunotherapies may have a beneficial impact on all patients or groups at risk, such as EPI, severe or necrotizing acute pancreatitis by reverting gut and immunologic dysbiosis, and improving quality of life.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Acute Pancreatitis
Exocrine Pancreatic Insufficiency
Gut Microbiota
Immunology
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Double-blind randomized placebo-controlled trial for patients with EPI after acute pancreatitis for PERT and collection of stool and blood samples before and after PERT/placebo
Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Participants
Investigators
For evaluation the response to PERT in patients with acute pancreatitis and EPI, the study will be doubleblind (for the patient who will not know which therapy he will be taking (PERT/placebo) and for the researchers responsible for sequencing and immunological analyses) randomized placebo-controlled clinical trial.
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Pancreatic Enzyme Replacement Therapy
Pancreatic Enzyme Replacement Therapy (PERT) 50000 Ph.U./meal + 25000 Ph.U./snack + Omeprazole 20mg once daily on fasting
Group Type
EXPERIMENTAL
Pancreatic Enzyme Replacement Therapy
Intervention Type
DRUG
Pancreatic Enzyme Replacement Therapy (PERT) 50000 Ph.U./meal + 25000 Ph.U./snack + Omeprazole 20mg once daily on fasting
Placebo
Placebo + Omeprazole 20mg once daily on fasting
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
Placebo + Omeprazole 20mg once daily on fasting
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pancreatic Enzyme Replacement Therapy
Pancreatic Enzyme Replacement Therapy (PERT) 50000 Ph.U./meal + 25000 Ph.U./snack + Omeprazole 20mg once daily on fasting
Intervention Type
DRUG
Placebo
Placebo + Omeprazole 20mg once daily on fasting
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
kreon
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Definitive diagnosis of acute pancreatitis, according to revised Atlanta criteria 2012.
Exclusion Criteria
* Age \<18years
* History of allergy, hypersensitivity or contraindication to use of PERT
* Prior acute pancreatitis
* Other causes that may occur with EPI, including celiac disease, diabetic gastroparesis, chronic pancreatitis, cystic fibrosis, pancreatic neoplasia, ampulloma, somatostatinoma, somatostatin analog therapy, small bowel pathology, inflammatory bowel disease, and rare diseases associated with exocrine pancreatic insufficiency (Zollinger-Ellison syndrome, Shwachman-Diamond syndrome, Johanson-Blizzard syndrome)
* Prior gastrointestinal or pancreatic surgery or endoscopic/surgical therapy for obesity
* medication with orlistat or acarbose
* Respiratory pathology (severe chronic obstructive pulmonary disease), hepatic (Child-Pugh C cirrhosis) or biliary (obstructive jaundice) severe pathology
* Non-compliance for PERT (when indicated)
* Uncontrolled thyroid pathology
* Refusal/incapacity to give informed consent
* Follow-up period \<12months after acute pancreatitis diagnosis
* History of allergy, hypersensitivity or contraindication to use of PERT
* Prior acute pancreatitis
* Other causes that may occur with EPI, including celiac disease, diabetic gastroparesis, chronic pancreatitis, cystic fibrosis, pancreatic neoplasia, ampulloma, somatostatinoma, somatostatin analog therapy, small bowel pathology, inflammatory bowel disease, and rare diseases associated with exocrine pancreatic insufficiency (Zollinger-Ellison syndrome, Shwachman-Diamond syndrome, Johanson-Blizzard syndrome)
* Prior gastrointestinal or pancreatic surgery or endoscopic/surgical therapy for obesity
* medication with orlistat or acarbose
* Respiratory pathology (severe chronic obstructive pulmonary disease), hepatic (Child-Pugh C cirrhosis) or biliary (obstructive jaundice) severe pathology
* Non-compliance for PERT (when indicated)
* Uncontrolled thyroid pathology
* Refusal/incapacity to give informed consent
* Follow-up period \<12months after acute pancreatitis diagnosis
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Coimbra
OTHER
Sponsor Role
collaborator
Unidade Local de Saúde de Coimbra, EPE
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Marta Isabel da Fonseca Gravito Soares
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Marta Gravito-Soares, MD
Role: PRINCIPAL_INVESTIGATOR
Unidade Local de Saúde de Coimbra, EPE
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centro Hospitalar e Universitário de Coimbra, E.P.E.
Coimbra, , Portugal
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
Portugal
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Marta Gravito-Soares, MD
Role: primary
Pedro Figueiredo, PhD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol. 2019 Aug;16(8):479-496. doi: 10.1038/s41575-019-0158-2.
Reference Type
RESULT
Roberts SE, Morrison-Rees S, John A, Williams JG, Brown TH, Samuel DG. The incidence and aetiology of acute pancreatitis across Europe. Pancreatology. 2017 Mar-Apr;17(2):155-165. doi: 10.1016/j.pan.2017.01.005. Epub 2017 Jan 19.
Reference Type
RESULT
Xiao AY, Tan ML, Wu LM, Asrani VM, Windsor JA, Yadav D, Petrov MS. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016 Sep;1(1):45-55. doi: 10.1016/S2468-1253(16)30004-8. Epub 2016 Jun 28.
Reference Type
RESULT
Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.
Reference Type
RESULT
Hollemans RA, Hallensleben NDL, Mager DJ, Kelder JC, Besselink MG, Bruno MJ, Verdonk RC, van Santvoort HC; Dutch Pancreatitis Study Group. Pancreatic exocrine insufficiency following acute pancreatitis: Systematic review and study level meta-analysis. Pancreatology. 2018 Apr;18(3):253-262. doi: 10.1016/j.pan.2018.02.009. Epub 2018 Feb 20.
Reference Type
RESULT
Huang W, de la Iglesia-Garcia D, Baston-Rey I, Calvino-Suarez C, Larino-Noia J, Iglesias-Garcia J, Shi N, Zhang X, Cai W, Deng L, Moore D, Singh VK, Xia Q, Windsor JA, Dominguez-Munoz JE, Sutton R. Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis. Dig Dis Sci. 2019 Jul;64(7):1985-2005. doi: 10.1007/s10620-019-05568-9. Epub 2019 Jun 4.
Reference Type
RESULT
Gravito-Soares M, Gravito-Soares E, Gomes D, Almeida N, Tome L. Red cell distribution width and red cell distribution width to total serum calcium ratio as major predictors of severity and mortality in acute pancreatitis. BMC Gastroenterol. 2018 Jul 5;18(1):108. doi: 10.1186/s12876-018-0834-7.
Reference Type
RESULT
Das SL, Singh PP, Phillips AR, Murphy R, Windsor JA, Petrov MS. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut. 2014 May;63(5):818-31. doi: 10.1136/gutjnl-2013-305062. Epub 2013 Aug 8.
Reference Type
RESULT
Ahmed Ali U, Issa Y, Hagenaars JC, Bakker OJ, van Goor H, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Brink MA, Schaapherder AF, Dejong CH, Spanier BW, Heisterkamp J, van der Harst E, van Eijck CH, Besselink MG, Gooszen HG, van Santvoort HC, Boermeester MA; Dutch Pancreatitis Study Group. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis. Clin Gastroenterol Hepatol. 2016 May;14(5):738-46. doi: 10.1016/j.cgh.2015.12.040. Epub 2016 Jan 6.
Reference Type
RESULT
Pendharkar SA, Salt K, Plank LD, Windsor JA, Petrov MS. Quality of life after acute pancreatitis: a systematic review and meta-analysis. Pancreas. 2014 Nov;43(8):1194-200. doi: 10.1097/MPA.0000000000000189.
Reference Type
RESULT
Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology. 2015 Nov;149(6):1490-1500.e1. doi: 10.1053/j.gastro.2015.07.066. Epub 2015 Aug 20.
Reference Type
RESULT
Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1220-1228.e4. doi: 10.1016/j.cgh.2018.01.027. Epub 2018 Jan 31.
Reference Type
RESULT
Loser C, Brauer C, Aygen S, Hennemann O, Folsch UR. Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test. Scand J Gastroenterol. 1998 Mar;33(3):327-34. doi: 10.1080/00365529850170946.
Reference Type
RESULT
Adolph TE, Mayr L, Grabherr F, Schwarzler J, Tilg H. Pancreas-Microbiota Cross Talk in Health and Disease. Annu Rev Nutr. 2019 Aug 21;39:249-266. doi: 10.1146/annurev-nutr-082018-124306.
Reference Type
RESULT
Zhu Y, He C, Li X, Cai Y, Hu J, Liao Y, Zhao J, Xia L, He W, Liu L, Luo C, Shu X, Cai Q, Chen Y, Lu N. Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. J Gastroenterol. 2019 Apr;54(4):347-358. doi: 10.1007/s00535-018-1529-0. Epub 2018 Dec 5.
Reference Type
RESULT
Leal C, Almeida N. Predicting Severity in Acute Pancreatitis: A Never-Ending Quest.... GE Port J Gastroenterol. 2019 Jul;26(4):232-234. doi: 10.1159/000499680. Epub 2019 Apr 16. No abstract available.
Reference Type
RESULT
Almeida N, Fernandes A, Casela A. Predictors of Severity and In-Hospital Mortality for Acute Pancreatitis: Is There Any Role for C-Reactive Protein Determination in the First 24 Hours? GE Port J Gastroenterol. 2015 Jul 3;22(5):187-189. doi: 10.1016/j.jpge.2015.05.004. eCollection 2015 Sep-Oct. No abstract available.
Reference Type
RESULT
Rao SA, Kunte AR. Interleukin-6: An Early Predictive Marker for Severity of Acute Pancreatitis. Indian J Crit Care Med. 2017 Jul;21(7):424-428. doi: 10.4103/ijccm.IJCCM_478_16.
Reference Type
RESULT
Deng LH, Hu C, Cai WH, Chen WW, Zhang XX, Shi N, Huang W, Ma Y, Jin T, Lin ZQ, Jiang K, Guo J, Yang XN, Xia Q. Plasma cytokines can help to identify the development of severe acute pancreatitis on admission. Medicine (Baltimore). 2017 Jul;96(28):e7312. doi: 10.1097/MD.0000000000007312.
Reference Type
RESULT
Nieminen A, Maksimow M, Mentula P, Kyhala L, Kylanpaa L, Puolakkainen P, Kemppainen E, Repo H, Salmi M. Circulating cytokines in predicting development of severe acute pancreatitis. Crit Care. 2014 May 21;18(3):R104. doi: 10.1186/cc13885.
Reference Type
RESULT
de la Iglesia-Garcia D, Huang W, Szatmary P, Baston-Rey I, Gonzalez-Lopez J, Prada-Ramallal G, Mukherjee R, Nunes QM, Dominguez-Munoz JE, Sutton R; NIHR Pancreas Biomedical Research Unit Patient Advisory Group. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut. 2017 Aug;66(8):1354-1355. doi: 10.1136/gutjnl-2016-312529. Epub 2016 Dec 9.
Reference Type
RESULT
Dominguez-Munoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford). 2009 Dec;11 Suppl 3(Suppl 3):3-6. doi: 10.1111/j.1477-2574.2009.00132.x.
Reference Type
RESULT
Kahl S, Schutte K, Glasbrenner B, Mayerle J, Simon P, Henniges F, Sander-Struckmeier S, Lerch MM, Malfertheiner P. The effect of oral pancreatic enzyme supplementation on the course and outcome of acute pancreatitis: a randomized, double-blind parallel-group study. JOP. 2014 Mar 10;15(2):165-74. doi: 10.6092/1590-8577/797.
Reference Type
RESULT
Dominguez-Munoz JE, Nieto-Garcia L, Lopez-Diaz J, Larino-Noia J, Abdulkader I, Iglesias-Garcia J. Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis. BMC Cancer. 2018 May 5;18(1):534. doi: 10.1186/s12885-018-4439-x.
Reference Type
RESULT
Layer P, Kashirskaya N, Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J Gastroenterol. 2019 May 28;25(20):2430-2441. doi: 10.3748/wjg.v25.i20.2430.
Reference Type
RESULT
American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S13-S27. doi: 10.2337/dc18-S002.
Reference Type
RESULT
Dominguez-Munoz JE. Diagnosis and treatment of pancreatic exocrine insufficiency. Curr Opin Gastroenterol. 2018 Sep;34(5):349-354. doi: 10.1097/MOG.0000000000000459.
Reference Type
RESULT
Ferreira PL. [Development of the Portuguese version of MOS SF-36. Part I. Cultural and linguistic adaptation]. Acta Med Port. 2000 Jan-Apr;13(1-2):55-66. Portuguese.
Reference Type
RESULT
Pais-Ribeiro J, Pinto C, Santos C. Validation study of the portuguese version of the QLC-C30-V.3. Psic, Saúde & Doenças. 2008;9(1):89-102.
Reference Type
RESULT
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
EPInAP
Identifier Type: -
Identifier Source: org_study_id