Trial Outcomes & Findings for New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy (NCT NCT01550809)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

12 participants

Primary outcome timeframe

The whole experiment, i.e. 5 hours

Results posted on

2012-08-29

Participant Flow

Twelve patients were recruited in this two-way, crossover study. One factor was the type of the insulin bolus administered (iBolus or tBolus). The other factor was the amount of carbohydrates (Low- or High-CHO meal) ingested. Recruitment started in February 2010 and was terminated by the end of June 2011

Subjects received the i- or the tBolus on the first meal study (either Low or High CHO), according to one of the following sequences: 1. iBolus first+low CHO first 2. iBolus first+high CHO first 3. tBolus first+low CHO first 4. tBolus first+high CHO first Each one of the four meal tests was performed 1-2 weeks apart from the others

Participant milestones

Participant milestones
Measure	tBolus (Traditional Bolus) Traditional mealtime bolus based on the individual insulin-to-CHO ratio	iBolus (CGM-based Insulin Administration) This is a continuous glucose monitoring (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.
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

New Strategies for Postprandial Glycemic Control Using Insulin Pump Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	tBolus (Traditional Bolus) n=6 Participants Traditional mealtime bolus based on the individual insulin-to-CHO ratio	iBolus (CGM-based Insulin Administration) n=6 Participants This is a continuous glucose monitoring (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.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	43.6 years STANDARD_DEVIATION 6.8 • n=5 Participants	40.3 years STANDARD_DEVIATION 7.9 • n=7 Participants	41.8 years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Spain	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: The whole experiment, i.e. 5 hours

Population: This was a proof-of-concept study. However, as an estimation of N, a two-sided t-test achieved 84% power to infer that the mean difference was not 0 when the total sample size of a 2x2 crossover design was 12, the actual mean difference in the AUC-PG0-5 h was 100mg\*dl-1\*h, the square root of the within mean square error was 75.0 and alpha was 0.05.

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).

Outcome measures

Outcome measures
Measure	tBolus (Traditional Bolus) n=12 Participants Traditional mealtime bolus based on the individual insulin-to-CHO ratio	iBolus (CGM-based Insulin Administration) n=12 Participants This is a continuous glucose monitoring (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.
The Area Under the Curve (AUC) of Plasma Glucose (PG) Concentrations During the 5-hour Postprandial Period (AUC-PG0-5 h).	724.6 mg*h/dl Standard Deviation 198.7	668.8 mg*h/dl Standard Deviation 162.7

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	tBolus (Traditional Bolus) n=12 Participants Traditional mealtime bolus based on the individual insulin-to-CHO ratio	iBolus (CGM-based Insulin Administration) n=12 Participants This is a continuous glucose monitoring (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.
The Area Under the Curve (AUC) of the Glucose Infusion Rate (GIR) During the 5-hour Postprandial Period (AUC-GIR0-5h).	55.0 mg/kg Standard Deviation 103.3	119.6 mg/kg Standard Deviation 167.0

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	tBolus (Traditional Bolus) n=12 Participants Traditional mealtime bolus based on the individual insulin-to-CHO ratio	iBolus (CGM-based Insulin Administration) n=12 Participants This is a continuous glucose monitoring (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.
The Area Under the Curve (AUC) of Plasma Glucose (PG) Above the Threshold of 140 mg/dl (AUC-PG>140).	111.1 mg*h/dl Standard Deviation 176.6	89.3 mg*h/dl Standard Deviation 144.0

Adverse Events

tBolus (Traditional Bolus)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

iBolus (CGM-based Insulin Administration)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Francisco Javier Ampudia Blasco

Departamento de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia, Universitat de València, Valencia, Spain

Phone: +34 96 3862665

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place