New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy

This study has been completed.
Sponsor:
Collaborators:
European Union
Ministerio de Ciencia e Innovación, Spain
Information provided by (Responsible Party):
Fundación para la Investigación del Hospital Clínico de Valencia
ClinicalTrials.gov Identifier:
NCT01550809
First received: February 28, 2012
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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 its efficiency be demonstrated clinically, the method could be incorporated in advanced sensor augmented pumps as well as feedforward action in closed-loop control algorithms for the artificial pancreas, in future work.


Condition Intervention Phase
Type 1 Diabetes
Other: iBolus
Other: tBolus (traditional bolus)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy: Feasibility of Insulin Dosing Based on Information From Continuous Glucose Monitoring

Resource links provided by NLM:


Further study details as provided by Fundación para la Investigación del Hospital Clínico de Valencia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 the insulin administration and during the whole 5-hour postprandial period (300 minutes).


  • 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. ] [ Designated as safety issue: Yes ]

    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 minute following the insulin administration and during the whole 5-hour postprandial period (300 minutes).



Secondary Outcome Measures:
  • The Area Under the Curve (AUC) of Plasma Glucose (PG) Above the Threshold of 140 mg/dl (AUC-PG>140). [ Time Frame: The whole experiment, i.e. the 5-hour postprandial period ] [ Designated as safety issue: No ]

    The AUC-PG>140 during the 5-hour period following the meal test represents the hyperglycemic risk related to the modality of prandial insulin administration.

    Plasma glucose (PG) for calculation of AUC-PG>140 was measured every 15 minutes following the insulin administration and during the whole 5-hour postprandial period (300 minutes).



Enrollment: 12
Study Start Date: February 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: tBolus (traditional bolus)
Traditional mealtime insulin bolus based on the individual insulin-to-CHO ratio
Other: tBolus (traditional bolus)
Insulin bolus dose calculated using the standard procedure based on the insulin-to-carbohydrate ratio
Experimental: iBolus (CGM-based insulin administration)
This is a CGM-based algorithm for prandial insulin administration. An individual patient's model characterizing a 5-hour postprandial period (0-5h PP) is obtained from a 6-day CGM period. A model with interval parameters accounting for patient's variability is calculated considering 20% uncertainty in insulin sensitivity and 10% in carbohydrates (CHO) estimation. Based on this model, constraints on plasma glucose are posed and a set-inversion problem lead to a set of solutions (the iBolus) that contains a bolus insulin dose, a specific mealtime basal insulin dose and the time for restoration of basal to baseline values.
Other: iBolus
Insulin bolus calculated from data obtained through CGM

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged between 18 and 60 years
  • Under CSII treatment for at least six months before Visit 1
  • Body mass index of between 18 and 35 kg/m2
  • HbA1c 6.0-8.5% at Visit 1
  • Normal laboratory values, ECG, and vital signs unless the investigator considered an abnormality to be clinically irrelevant
  • Women postmenopausal or using contraception judged by the investigator to be adequate (e.g., oral contraceptives, intra-uterine device or surgical treatment), with a negative urine pregnancy tests

Exclusion Criteria:

  • Pregnancy and lactation
  • History of hypersensitivity to the study medications or to drugs with similar chemical structures
  • Hypoglycemia unawareness
  • Progressive fatal diseases
  • History of drug or alcohol abuse
  • History of positive HIV or hepatitis B or C test
  • Impaired hepatic function, as shown by, but not limited to, SGPT or SGOT of more than twice the upper limit of the normal range at visit 1
  • Impaired renal function, as shown by, but not limited to, serum creatinine > 1.5 mg/dL at visit 1
  • Clinically relevant microvascular, cardiovascular, hepatic, neurologic, endocrine or other major systemic diseases other than T1DM which could hinder implementation of the clinical study protocol or interpretation of the study results
  • Pre-planned surgery during the study
  • Blood donation of more than 500 ml during the past three months for men, or during the past six months for women
  • Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
  • Subject unlikely to comply with clinical study protocol, e.g., uncooperative attitude, inability to return for follow-up visits, or poor likelihood of completing the study
  • Receipt of an experimental drug or use of an experimental device during the past 30 days.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01550809

Locations
Spain
Hospital Clínico Universitario
Valencia, Spain, 46010
Sponsors and Collaborators
Fundación para la Investigación del Hospital Clínico de Valencia
European Union
Ministerio de Ciencia e Innovación, Spain
Investigators
Principal Investigator: Francisco Javier Ampudia-Blasco, MD, PhD Fundación INCLIVA, Hospital Clínico Universitario de Valencia
  More Information

Additional Information:
No publications provided

Responsible Party: Fundación para la Investigación del Hospital Clínico de Valencia
ClinicalTrials.gov Identifier: NCT01550809     History of Changes
Other Study ID Numbers: FP7-PEOPLE-2009-IEF #252085, DPI2010-20764-C02-01
Study First Received: February 28, 2012
Results First Received: June 5, 2012
Last Updated: August 20, 2012
Health Authority: Spain: Ethics Committee

Keywords provided by Fundación para la Investigación del Hospital Clínico de Valencia:
T1DM
CSII
CGM
postprandial control
glycemic variability
Prandial insulin dosing in Type 1 diabetes treated with continuous subcutaneous insulin infusion

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014