Clinical Outcome After Total Pancreatectomy With Islet Autotransplantation

Study Overview
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Brief Summary
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A total pancreatectomy with islet autotransplantation (TPIAT) can be performed for a number of benign indications, such as chronic pancreatitis. In the current standard of treatment, after non-invasive, endoscopic efforts and other surgical options to relieve the pain, a total pancreatectomy is a last resort option. The pancreas is surgically removed during this procedure. Afterwards, the patient will have diabetes mellitus that is usually difficult to control with dependency on exogenous insulin administration. In TPIAT, a total pancreatectomy is followed by islet isolation from the resected pancreas and autotransplantation of these islets into the liver by means of a transhepatic intraportal islet infusion. Depending on the number and quality of islets, TPIAT may lead to full islet function so that no anti-hyperglycemic therapy is necessary or to partial islet function necessitating anti-hyperglycemic therapy. This can be only oral agents with reasonable islet function or complex insulin regimes with poor islet function. However, even with partial Islet function, glycemic control is easier with a lower risk of hypoglycemic events and diabetes-related complications, and an overall improvement of quality of life. In this cohort, the endocrine function and glycemic variability will be monitored over time (up to 15 years). Additionally, pain scores, pain perception and central sensitization, quality of life, exocrine pancreatic insufficiency and diabetes-related stress will be monitored.

Official Title
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Clinical Outcome After Total Pancreatectomy With Islet Autotransplantation

Conditions
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Islets of Langerhans Transplantation, Pancreatitis, Chronic, Diabetes Mellitus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients referred for TPIAT or TPIAT performed since 2014 Active and/or passive understanding of the Dutch language Willingness to wear a FGM or CGM device at least in the 2 weeks prior to TPIAT, first 3 months after TPIAT and for 2 weeks before yearly clinical visits. Exclusion Criteria: Known malignancies of the pancreas

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Referred for Total pancreatectomy with islet autotransplantation<br>Followed up for up for 15 years after TPIAT. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic islet function | AUC(0-120min) C-peptide during mixed meal tolerance test (MMTT) | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic islet function | Maximum C-peptide concentration during MMTT | Up to 15 years | 
| Pancreatic islet function | Difference in basal and maximum C-peptide concentration during MMTT | Up to 15 years | 
| Glycemic control | Time below range, time in range, time above range as determined by flash glucose monitoring (FGM) or continuous glucose measurement (CGM) | Up to 15 years | 
| Glycemic control | Standard deviation determined by FGM or CGM | Up to 15 years | 
| Glycemic control | HbA1c as determined in the blood and estimated by FGM or CGM | Up to 15 years | 
| Glycemic control | Insulin requirements (IU/kg/day) | Up to 15 years | 
| Quality of life | assessed by MOS Short Form 36 (SF-36) questionnaire | Up to 15 years | 
| Quality of life | assessed by EQ-5D questionnaire | Up to 15 years | 
| Diabetes-related stress | assessed by Problem Areas in Diabetes (PAID) questionnaire | Up to 15 years | 
| Exocrine pancreatic insufficiency | assessed by Pancreas Exocrine Insufficiency Questionnaire (PEI-Q) | Up to 15 years | 
| Pancreas-related pain | assessed by COMPAT-SF questionnaire | Up to 15 years | 
| Pancreas-related pain | assessed by Izbicki questionnaire | Up to 15 years | 
| Pain perception and central sensitization | assessed by Quantitative Sensory Testing | Baseline, MOS 6 | 
| Opioid usage | Morphine Milligram equivalents | Up to 15 years | 
| Frequency of surgical complications | Early (<3 months) or late (>3 months) | Up to 15 years | 
| Frequency of complications attributed to islet transplantation |  | Up to 15 years | 
| Histological examination pancreas | Degree of fibrosis, acinar cell atrophy, inflammation and nesidioblastosis | After biopsy during islet isolation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TPIAT, beta-cell function, total pancreatectomy, autologous islet transplantation, c-peptide