Clinical trial NCT06346366: Glucose Control Through a Bihormonal Artificial Pancreas in Patients After Total Pancreatectomy
Official title: Glucose Control Through a Bihormonal Artificial Pancreas in Patients After Total Pancreatectomy (PANORAMA): Randomized Controlled Crossover Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pancreatic Neoplasms
Type 3c Diabetes
Total Pancreatectomy
Keywords: Bihormonal artificial pancreas
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2024-04-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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

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.

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.

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.

Primary outcomes:
measure: Time in range
timeFrame: During open and closed loop treatment (both 3 months)
Secondary outcomes:
measure: Efficacy of open and closed loop system
timeFrame: During open and closed loop treatment (both 3 months)
measure: Efficacy of open and closed loop system
timeFrame: During open and closed loop treatment (both 3 months)
measure: Efficacy of open and closed loop system
timeFrame: During open and closed loop treatment (both 3 months)
measure: Efficacy of open and closed loop system
timeFrame: During open and closed loop treatment (both 3 months)
measure: Efficacy of open and closed loop system
timeFrame: During open and closed loop treatment (both 3 months)
measure: Adverse events and device issues associated with closed loop system with BIHAP
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - WHO-5
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - EQ-5D-5L
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - DTSQc andDTSQs
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - PAID-20
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - HFS-II
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - PSQI
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - INSPIRE
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - Hypoglycaemia unawareness
timeFrame: During open and closed loop treatment (both 3 months)
measure: Patient reported outcomes on quality of life - benefits and disadvantages of BIHAP treatment
timeFrame: During open and closed loop treatment (both 3 months)
Other outcomes:
measure: Other treatment endpoints - daily insulin and glucagon use
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - activity of BIHAP algorithm
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - daily insulin use
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - treatment related actions
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - demographics
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - demographics
timeFrame: During open and closed loop treatment (both 3 months)
measure: Other treatment endpoints - concomitant medication
timeFrame: During open and closed loop treatment (both 3 months)
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
References: