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

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

NCT ID: NCT06346366

Condition: Pancreatic Neoplasms
Type 3c Diabetes
Total Pancreatectomy

Conditions: Official terms:
Pancreatic Neoplasms
Pancrelipase

Conditions: Keywords:
Bihormonal artificial pancreas

Study type: Interventional

Study phase: Phase 3

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Crossover Assignment

Intervention model description: 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.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Bihormonal artificial pancreas (BIHAP) / closed loop
Description: 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.
Arm group label: Closed loop
Arm group label: Open loop

Other name: Current regular diabetes treatment / open loop

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.

Detailed description: Rationale: Insulin dependent diabetes after total pancreatectomy (TP) is difficult to manage due to the complete absence of alfa and beta cells. In a recent pilot study in 10 patients after total pancreatectomy, treatment with a bihormonal closed loop system was safe and resulted in better glucose control compared to current open loop therapy. Objective: To assess the efficacy of a 3-month treatment with a bihormonal artificial pancreas (BIHAP) in patients after total pancreatectomy compared to current diabetes care. Secondary objectives are to assess the safety of BIHAP treatment; quality of life during BIHAP treatment and additional efficacy parameters. Study design: PANORAMA is a randomized, cross-over trial performed in an outpatient setting comparing closed loop diabetes treatment with BIHAP to open loop with current diabetes care (i.e., insulin pump or pen therapy) in 40 adults after TP. Patients will be recruited from Dutch Pancreatic Cancer Group hospitals and randomized to a 3-month treatment period with the BIHAP (preceded by a 5-day training period) or a 3-month treatment with their current diabetes care. Hereafter, all 40 patients will cross over. Study population: This trial will comprise in total 40 adult patients with insulin dependent diabetes at least three months after total pancreatectomy. Intervention: The intervention is 3 months closed loop control of blood glucose with the BIHAP. Patients complete a 5-day training period before the intervention period will start. The BIHAP contains a self-learning algorithm which automatically maintains the glucose levels within target limits via subcutaneous administration of insulin (Humalog®) and glucagon. The control arm (open loop) consists of standard treatment for diabetes with continuous subcutaneous insulin infusion or insulin injections for 3 months. After a wash-out period of 3 months, all patients will crossover to the other study arm. Main study parameters/endpoints: The primary endpoint will be time (in %) spent in the normal glucose range (3.9 mmol/l - 10.0 mmol/l). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will have to wear the prototype with two subcutaneous sensors and infusion sets continuously. There are no major risks associated with this study. The most prominent risk is failure of the BIHAP to regulate the plasma glucose concentration properly, which can result in hypo- or hyperglycemia. This may be caused by failure of the algorithm, technical failure or due to incorrect glucose measurements. However, with multiple risk control measures the risk for the patients is minimized. The system comprises a controller, a separate safety processor, as well as multiple alerts that are built in the system. The potential benefits for each patient include a significantly better glycemic control, as well as improved quality of life because the BIHAP system completely takes over the glucose regulation, thereby minimizing the burden of life with diabetes.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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. Exclusion Criteria: - 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.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: Accepts Healthy Volunteers

Locations:

Facility:
Name: Amsterdam UMC

Address:
City: Amsterdam
Zip: 1081 HV
Country: Netherlands

Start date: April 25, 2023

Completion date: April 1, 2024

Lead sponsor:
Agency: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Agency class: Other

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

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06346366