New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy

NCT01550809 | Completed Phase 3 Results

• 2 other identifiers: FP7-PEOPLE-2009-IEF #252085DPI2010-20764-C02-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

T1DM; CSII; CGM; postprandial control; glycemic variability; Prandial insulin dosing in Type 1 diabetes treated with continuous subcutaneous insulin infusion

Outcome Measures

Primary Outcomes (2)

• The Area Under the Curve (AUC) of Plasma Glucose (PG) Concentrations During the 5-hour Postprandial Period (AUC-PG0-5 h).

  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 whole experiment, i.e. 5 hours

• The Area Under the Curve (AUC) of the Glucose Infusion Rate (GIR) During the 5-hour Postprandial Period (AUC-GIR0-5h).

  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).

  The whole experiment, i.e. 5 hours.

Secondary Outcomes (1)

• The Area Under the Curve (AUC) of Plasma Glucose (PG) Above the Threshold of 140 mg/dl (AUC-PG>140).

  The whole experiment, i.e. the 5-hour postprandial period

Study Arms (2)

tBolus (traditional bolus)

ACTIVE COMPARATOR

Traditional mealtime insulin bolus based on the individual insulin-to-CHO ratio

Other: tBolus (traditional bolus)

iBolus (CGM-based insulin administration)

EXPERIMENTAL

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

Interventions

iBolus OTHER

Insulin bolus calculated from data obtained through CGM

iBolus (CGM-based insulin administration)

tBolus (traditional bolus) OTHER

Insulin bolus dose calculated using the standard procedure based on the insulin-to-carbohydrate ratio

tBolus (traditional bolus)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead
• European Union: collaborator
• Ministerio de Ciencia e Innovación, Spain: collaborator

Study Sites (1)

Hospital Clínico Universitario

Valencia, Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Francisco Javier Ampudia Blasco
• Organization: Departamento de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia, Universitat de València, Valencia, Spain

Francisco.J.Ampudia@uv.es

+34 96 3862665

Study Officials

• Francisco Javier Ampudia-Blasco, MD, PhD

  Fundación INCLIVA, Hospital Clínico Universitario de Valencia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2012
• First Posted: March 12, 2012
• Study Start: February 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: August 29, 2012
• Results First Posted: August 29, 2012

Record last verified: 2012-08

Locations

ES (1)