Exocrine Pancreatic Insufficiency After Acute Pancreatitis and Pancreatic Enzyme Replacement Therapy

NCT05480241 | Unknown

• 1 other identifier: EPInAP
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Pancreatitis; Exocrine Pancreatic Insufficiency; Gut Microbiota; Immunology

Outcome Measures

Primary Outcomes (4)

• When to start PERT assessed by the time, in days, between acute pancreatitis diagnosis and EPI diagnosis in patients with EPI following acute pancreatitis

  A standardized protocol will be applied for both groups differing only in drug used (PERT or placebo). To evaluate when to start PERT we will determine the time between acute pancreatitis diagnosis and EPI diagnosis, in days. Searching for EPI will take place up to 12 months after acute pancreatitis diagnosis.

  Up to 12 months

• PERT efficacy assessed by % of successful treatments in patients with EPI following acute pancreatitis

  A standardized protocol will be applied for both groups differing only in drug used (PERT or placebo). The PERT dose will be the one agreed for EPI for benign pancreatic pathologies associated with proton pump inhibitor (PPI). PERT efficacy will be assessed by the % of successful treatments in patients with EPI diagnosis after acute pancreatitis, using the test that was positive for EPI diagnosis (fecal elastase-1, 13 C Mixed Triglyceride Breath Test or Fecal Fat Quantitative Test). Efficacy corresponds to the normalization of exocrine pancreatic function test and will be assessed by at 6 months post-randomization. The compliance of PERT will be checked in all follow-up visits.

  At 6 months after starting PERT

• PERT safety assessed by adverse effects according to Medical Dictionary for Regulatory Activities in patients with EPI following acute pancreatitis

  A standardized protocol will be applied for both groups differing only in drug used (PERT or placebo). The PERT dose will be the one agreed for EPI for benign pancreatic pathologies associated with proton pump inhibitor (PPI). PERT safety will be evaluated with the determination of adverse effects according to Medical Dictionary for Regulatory Activities (MedDRa will be evaluated in terms of visual analogic intolerance scale (0-10) for abdominal pain and other adverse events severity in relation to the influence on activities of daily life. PERT safety will be assessed at 6 months post-randomization. The compliance of PERT will be checked in all follow-up visits.

  At 6 months after starting PERT

• PERT duration assessed by the time of starting PERT to normalization of exocrine pancreatic function in patients with EPI following acute pancreatitis

  A standardized protocol will be applied for both groups differing only in drug used (PERT or placebo). The PERT dose will be the one agreed for EPI for benign pancreatic pathologies associated with proton pump inhibitor (PPI). The duration of PERT will be evaluated determining the time, in months, between EPI diagnosis after acute pancreatitis diagnosis and the normalization of exocrine pancreatic function, determined by the normalization of positive test diagnosing EPI (fecal elastase-1, 13 C Mixed Triglyceride Breath Test or Fecal Fat Quantitative Test), using the test that was positive for EPI diagnosis.

  At 6 months after starting PERT

Secondary Outcomes (7)

• Prevalence of exocrine pancreatic insufficiency (EPI) following acute pancreatitis assessed by the proportion and percentage of patients with EPI after acute pancreatitis diagnosis

  Up to 12 months

• Prevalence of endocrine pancreatic insufficiency (EnPI) following acute pancreatitis assessed by the proportion and % of patients with EnPI after acute pancreatitis diagnosis

  Up to 12 months

• Changes in gut microbiota profile using DNA sequencing of ribosomal 16S bacteria gene in acute pancreatitis, EPI following acute pancreatitis and after PERT assessed by the changes in composition and diversity of gut microbiota (OTU changes)

  Change from Baseline at 6 months after starting PERT

• Changes in Immunological profile assessed by study of cell populations in acute pancreatitis, EPI following acute pancreatitis diagnosis and after PERT

  Change from Baseline at 6 months after starting PERT

• Changes in quality of life in patients with EPI after acute pancreatitis, EPI following acute pancreatitis and after PERT assessed by quality of life scale appropriated to this condition - SF-36

  Change from Baseline at 6 months after starting PERT

Study Arms (2)

Pancreatic Enzyme Replacement Therapy

EXPERIMENTAL

Pancreatic Enzyme Replacement Therapy (PERT) 50000 Ph.U./meal + 25000 Ph.U./snack + Omeprazole 20mg once daily on fasting

Drug: Pancreatic Enzyme Replacement Therapy

Placebo

PLACEBO COMPARATOR

Placebo + Omeprazole 20mg once daily on fasting

Drug: Placebo

Interventions

Pancreatic Enzyme Replacement Therapy DRUG

Pancreatic Enzyme Replacement Therapy (PERT) 50000 Ph.U./meal + 25000 Ph.U./snack + Omeprazole 20mg once daily on fasting

Also known as: kreon

Pancreatic Enzyme Replacement Therapy

Placebo DRUG

Placebo + Omeprazole 20mg once daily on fasting

Placebo

Eligibility Criteria

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

You may qualify if:

• Definitive diagnosis of acute pancreatitis, according to revised Atlanta criteria 2012.

You may not qualify if:

• 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

Sponsors & Collaborators

• Unidade Local de Saúde de Coimbra, EPE: lead
• University of Coimbra: collaborator

Study Sites (1)

Centro Hospitalar e Universitário de Coimbra, E.P.E.

Coimbra, 3000-075, Portugal

RECRUITING

Related Publications (29)

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  RESULT

MeSH Terms

Conditions

Pancreatitis; Exocrine Pancreatic Insufficiency

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Study Officials

• Marta Gravito-Soares, MD

  Unidade Local de Saúde de Coimbra, EPE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Gravito-Soares, MD

CONTACT

(+351)239400483; ms18498@gmail.com

Pedro Figueiredo, PhD

CONTACT

(+351)239400483; pnf11@sapo.pt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: May 22, 2022
• First Posted: July 29, 2022
• Study Start: May 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: July 29, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)