NCT01550809

New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy: Feasibility of Insulin Dosing Based on Information From Continuous Glucose Monitoring

Completed Phase 3 Results posted Last updated 20 August 2012

What this trial tests

Phase 3 trial testing iBolus in Type 1 Diabetes in 12 participants. Completed in 1 June 2011.

Timeline

1 February 2010

Primary endpoint
1 June 2011

1 June 2011

Quick facts

Lead sponsor	Fundación para la Investigación del Hospital Clínico de Valencia
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	12
Start date	1 February 2010
Primary completion	1 June 2011
Estimated completion	1 June 2011
Sites	1 location across Spain

Drugs / interventions tested

• iBolus
• tBolus (traditional bolus)

Conditions studied

• Type 1 Diabetes — all drugs for Type 1 Diabetes →

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

Who can join

Adults 18 to 60, any sex, with Type 1 Diabetes. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• The Area Under the Curve (AUC) of Plasma Glucose (PG) Concentrations During the 5-hour Postprandial Period (AUC-PG0-5 h).
  Time frame: The whole experiment, i.e. 5 hours
  AUC-PG0-5 h (5-hour postprandial glucose following the mixed meal test) is a measure of the overall glucose-lowering efficacy of the insulin bolus. The lower the AUC-PG0-5 h without hypoglycemia, the greater the effectiveness of the prandial insulin administration to control the meal related glucose excursion. Plasma glucose (PG) for calculation of AUC-PG was measured every 15 minutes following t
• The Area Under the Curve (AUC) of the Glucose Infusion Rate (GIR) During the 5-hour Postprandial Period (AUC-GIR0-5h).
  Time frame: The whole experiment, i.e. 5 hours.
  The amount of glucose infused during the 5-hour postprandial period (AUC-GIR0-5h) is a measure of the hypoglycemic exposure associated with the modality of prandial insulin administration. Indeed, glucose will be infused only when patients are under a predefined blood glucose values (80 mg/dl) with a descending trend. Glucose infusion rate (GIR) for calculation of AUC-GIR was measured every minut

Sponsor's own description

Achieving near-normoglycemia has been established as the main objective for most patients with type 1 diabetes (T1DM). However, insulin dosing is an empirical process and its success is highly dependent on the patients' and physicians' skills, either with multiple daily injections (MDI) or with continuous subcutaneous insulin infusion (CSII, the gold standard of insulin treatment).

Postprandial glucose control is one of the most challenging issues in the everyday diabetes care. Indeed, postprandial glucose excursions are the major contributors to plasma glucose (PG) variability of subjects with (T1DM) and the poor reproducibility of postprandial glucose response is burdensome for both patients and healthcare professionals.

During the past 10-15 years, there has been an exponentially increasing intrusion of technology into diabetes care with the expectation of making life easier for patients with diabetes. Some tools have been developed to aid patients in the prandial bolus decision-making process, i.e. "bolus advisors", which have been implemented in insulin pumps and more recently in the newest generations of glucometers. Currently, the availability of continuous glucose monitoring (CGM) has opened new scenarios for improving glycemic control and increasing understanding of post-prandial glycemic response in patients with diabetes.

Results from clinical studies suggest that sensor-augmented pumps (SAP)may be effective in improving metabolic control, especially when included as part of structured educational programs resulting in patients' empowerment. Similarly, preliminary results from pilot studies indicate that automated glycemic control, especially during nighttime,based on information from CGM is feasible. However, automatic management of meal bolus is currently one of the main challenges found in clinical validations of the few existing prototypes of an artificial pancreas. Indeed, fully closed-loop systems where information about meals size and timing is not given to the system have shown poor performance, with postprandial glucose higher and post meal nadir glucose lower than desired. This has promoted other less-ambitious approaches, where prandial insulin is administered following meal announcement (semi closed-loop). However, despite the use of meal announcement, currently used algorithms for glucose control (the so-called PID and MPC), show results that are not yet satisfactory due to the risk of producing hypoglycemia.

One of the limitations of the current open-loop (bolus advisors) and closed-loop control strategies is that glycemic variability is not taken into account. As an example, settings of CSII consider inter-individual variation of the parameters (insulin/carbohydrates ratio, correction dose, etc.) but disregard the day-to-day intra-individual variability of postprandial glucose response. Availability of massive amount of information from CGM, together with mathematic tools, may allow for the characterization of the individual variability and the development of strategies to cope with the uncertainty of the glycemic response to a meal.

In this project, a rigorous clinical testing of a CGM-based, user-independent algorithm for prandial insulin administration will be carried out in type 1 diabetic patients treated with insulin CSII.

First of all, an individual patient's model characterizing a 5-hour postprandial period will be obtained from a 6-day CGM period. The model will account for a 20% uncertainty in insulin sensitivity and 10% variability in the estimation of the ingested carbohydrates. Based on this model (derived from CGM), a mealtime insulin dose will be calculated (referred as iBolus). Then, the same subjects will undergo standardized meal test studies comparing the administration of a traditional bolus (tBolus, based on insulin to CHO ratio, correction factor, etc.) with the CGM-based prandial insulin delivery (iBolus).

Significant advances in postprandial control are expected. Should

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Evaluation of a novel continuous glucose monitoring-based method for mealtime insulin dosing--the iBolus--in subjects with type 1 diabetes using continuous subcutaneous insulin infusion therapy: a randomized controlled trial.
   Rossetti P, Ampudia-Blasco FJ, Laguna A, Revert A, et al · · 2012 · cited 13× · PMID 23003329 · DOI 10.1089/dia.2012.0145