Clinical Outcome After Total Pancreatectomy With Islet Autotransplantation (TOPPER)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus; Islets of Langerhans Transplantation; Pancreatitis, Chronic

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients referred for TPIAT or who have underwent TPIAT since 2014.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Referred for Total pancreatectomy with islet autotransplantation; Followed up for up for 15 years after TPIAT.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Anticipated): March 1, 2047
• Study Completion (Anticipated): March 1, 2047

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: beta-cell function; c-peptide; total pancreatectomy; autologous islet transplantation; TPIAT
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic
• Other Study ID Numbers: NL74838.058.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No