Glucose Control Through a Bihormonal Artificial Pancreas in Patients After Total Pancreatectomy

NCT06346366 | Active Not Recruiting Phase 3

• 1 other identifier: NL.82557.018.22
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years total pancreatectomy is increasingly performed in selected patients due to the increasing use of preoperative chemotherapy, making more patients operable. After total pancreatectomy, all patients develop insulin dependent diabetes mellitus (IDDM). Glucose control in these patients is challenging due to the complete absence of both pancreatic insulin and glucagon secretion, and most patients report decreased quality of life due to fear of hypoglycemic events and the need for continuous glucose monitoring. The CE marked bihormonal artificial pancreas (BIHAP) provides continuous fully automatic glucose monitoring and administration of insulin and glucagon using a self-learning algorithm. In a recent pilot study (APPEL5+, NL.8871) the BIHAP was being compared to current diabetes treatment in 10 patients after total pancreatectomy. This trial demonstrated that treatment with BIHAP was safe and improved time spent in euglycemia significantly during one week treatment (78.30%, \[IQR 71.05%-82.61%\] vs. 57.38% \[IQR 52.38%-81.35%\], p=0.03). Now, larger randomized studies with a longer treatment period are necessary to confirm safety and efficacy of BIHAP for the treatment of diabetes in patients after total pancreatectomy, with sufficient attention for long-term glycemic control (HbA1c) and patient-reported outcomes. The PANORAMA trial will evaluate the efficacy of a 3-month treatment with BIHAP in 40 patients after total pancreatectomy as compared to a 3-month treatment period with current diabetes care in a randomized cross-over trial. Patients will be randomized to start with the BIHAP (after a training period) or current diabetes care (i.e. insulin pen or pump). Hereafter, all patients will cross over.

Conditions

Pancreatic Neoplasms; Type 3c Diabetes; Total Pancreatectomy

Keywords

Bihormonal artificial pancreas

Outcome Measures

Primary Outcomes (1)

• Time in range

  Time spent in euglycemia (glucose value 3.9-10.0 mmol/l or 70-180mg/dL) during BIHAP treatment

  During open and closed loop treatment (both 3 months)

Secondary Outcomes (15)

• Efficacy of open and closed loop system

  During open and closed loop treatment (both 3 months)

• Efficacy of open and closed loop system

  During open and closed loop treatment (both 3 months)

• Efficacy of open and closed loop system

  During open and closed loop treatment (both 3 months)

• Efficacy of open and closed loop system

  During open and closed loop treatment (both 3 months)

• Efficacy of open and closed loop system

  During open and closed loop treatment (both 3 months)

Other Outcomes (7)

• Other treatment endpoints - daily insulin and glucagon use

  During open and closed loop treatment (both 3 months)

• Other treatment endpoints - activity of BIHAP algorithm

  During open and closed loop treatment (both 3 months)

• Other treatment endpoints - daily insulin use

  During open and closed loop treatment (both 3 months)

Study Arms (2)

Open loop

ACTIVE COMPARATOR

The control arm (open loop) consists of standard treatment for diabetes with continuous subcutaneous insulin infusion or insulin injections for 3 months.

Device: Bihormonal artificial pancreas (BIHAP) / closed loop

Closed loop

EXPERIMENTAL

The intervention arm is 3 months closed loop control of blood glucose with the BIHAP. The BIHAP contains a self-learning algorithm which automatically maintains the glucose levels within target limits via subcutaneous administration of insulin (Humalog®) and glucagon. Patients complete a training period before the intervention period will start.

Device: Bihormonal artificial pancreas (BIHAP) / closed loop

Interventions

Bihormonal artificial pancreas (BIHAP) / closed loop DEVICE

The investigational device is a dual-hormonal fully closed loop system (BIHAP; industrial name AP® 5, Inreda Diabetic B.V.) which aims at optimally controlling plasma glucose levels. This BIHAP contains of two pumps for subcutaneous infusion of either insulin (Humalog, 3 ml pre-fill cartridge, Eli Lilly) or glucagon (GlucaGen, Novo Nordisk; 3.15 ml cartridge Accu-Chek Spirit, Roche) via an infusion set (Accu-Chek Insight Flex or AccuChek Flex Link, Roche), two subcutaneously placed glucose-sensors (Guardian, Medtronic) and an algorithm driving pump infusion rates based on the sensor input. Daily self-measurements of blood glucose (SMBGs; Accu-Chek Instant, Roche) are needed for calibration of the glucose sensors. The BIHAP-system has to be worn continuously, except while showering.

Also known as: Current regular diabetes treatment / open loop

Closed loop; Open loop

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Age ≥18 years
• Insulin dependent diabetes after total pancreatectomy (patients who previously participated in APPEL 5+ are allowed to be included)
• At least three months after total pancreatectomy
• Patients using flash or continuous glucose sensor (Free Style Libre, Guardian or Medtronic) ,willing to scan this sensor at least three times per day during the control period and to remove this sensor during BIHAP treatment
• Undergoing treatment with CSII or subcutaneous insulin injections.

You may not qualify if:

• Known or suspected allergy to trial product(s) or related products;
• Suboptimal clinical condition, for instance due to active postoperative surgical complications, including skin condition prohibiting needle insertion;
• Actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or device in the last 2 weeks before enrolment into this study, as per investigator judgment;
• Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening for other clinical trial related purposes;
• Current treatment with chemotherapy or when used less than 3 months prior to screening;
• BMI \> 35 kg/m2;
• HbA1c \> 97 mmol/ml (=11.0 %);
• Use of oral glucose-lowering medication;
• Limited ability to see, and to hear or feel alarms signals of the BIHAP;
• Use of acetaminophen (paracetamol) during the use of the BIHAP, as this may influence the sensor glucose measurements.
• Current pregnancy, breast feeding or planning to become pregnant during the trial or using ineffective birth control methods;
• Patients with a concomitant disease affecting metabolic control;
• Presence of a medical or psychiatric condition, longstanding serious adherence problems, anticipated problems in handing over diabetes control to a device or use of a medication that, in the judgment of the investigator, clinical protocol chair, or medical monitor, could compromise the results of the study or the safety of the participant.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Marc Besselink, Prof. Dr.

Model Details: Patients are randomized to a 3-month treatment period with the bihormonal artificial pancreas (BIHAP) (preceded by a training period) or a 3-month treatment with their current diabetes care. Hereafter, all patients will cross over.

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: April 4, 2024
• Study Start: April 25, 2023
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: April 4, 2024

Record last verified: 2024-03

Locations

NL (1)