Back to resultsEffect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus (PUMP)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Insulin glulisine
Insulin lispro
Insulin aspart
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1
Eligibility Criteria
Inclusion Criteria:
- Type 1 diabetic subjects
- Treated with insulin for at least 2 years and by CSII for at least 6 months
- Using the same insulin (insulin glulisine, insulin aspart or insulin lispro) in CSII for at least 3 months with the same external pump compatible with the 3 short acting insulin analogues used in the study
- Using the same type of infusion set (catheter and cannula) for at least 3 months
- Performing at least 3 blood glucose controls per day
- HbA1c < 8.5%
- Body mass index (BMI) < 35 kg/m²
- Ability and willingness to perform blood glucose and ketone monitoring using the Sponsor-provided combined glucose and ketone meter and patient diary at home
Exclusion Criteria:
- Diabetes other than Type 1
- Total daily dose of insulin greater than 90 U/day
- Using an insulin pump requiring pre-filled cartridges
- History of infection at infusion site requiring a drainage in the last 3 months
- History of severe episodes of ketosis requiring hospitalization in the last 6 months
- Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study. An ophthalmoscopic examination should have been performed in the 2 years prior to study entry
- Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method) or breastfeeding
- Treatment with systemic corticosteroids or medication known to influence insulin sensitivity in the 3 months prior to visit 1
- Treatment with antidiabetic drug other than insulin in the 3 months prior to visit 1
- Likelihood of requiring treatments during the study which are not permitted
- Treatment with an investigational product in the 30 days prior to visit 1
- History of sensitivity to the study drugs or to drugs with a similar chemical structure
- Presence of any condition (medical, including clinically significant abnormal laboratory test, psychological, social or geographical) actual or anticipated that the Investigator feels would compromise the patient safety or limit his/her successful participation in the study
- Night shift workers
- Impaired renal function as shown by serum creatinine ≥1.5 mg/dL (133 μmol/L) or ≥1.4 mg/dL (124 μmol/L) in men and women, respectively
- Impaired hepatic function as shown by Alanine aminotransferase (ALT) and/or Aspart aminotransferase (AST) greater than three times the upper limit of normal range)
- Alcohol or drug abuse in the last year
- Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
sequence 1
Sequence 2
Sequence 3
Arm Description
sequence 1: insulin glulisine / insulin aspart / insulin lispro.
Sequence 2: insulin aspart / insulin lispro / insulin glulisine
Sequence 3: insulin lispro / insulin glulisine / insulin aspart
Outcomes
Primary Outcome Measures
Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Secondary Outcome Measures
Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Percentage of Patients With at Least One Unexplained Hyperglycemia
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Monthly Rate of Unexplained Hyperglycemia
Percentage of Patients With at Least One Confirmed Infusion Set Occlusion
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Monthly Rate of Confirmed Infusion Set Occlusion
Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).
Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l
Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).
Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l
Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year
Symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration.
Rate of Severe Symptomatic Hypoglycemia Per Patient-year
Severe symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia in which the patient required assistance of another person and one of the following:
the event was associated with a measured blood glucose level below 36 mg/dL
or event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.
Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year
Nocturnal Symptomatic hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration which occurs while the patient is asleep, after bedtime and before getting up in the morning.
Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site
Infection: local reaction at the infusion site requiring local or systemic antibiotherapy, or local drainage as per Investigator judgment.
Site inflammation or erythema: local reaction at the infusion site with no need for local or systemic antibiotherapy as per Investigator judgment.
Pruritis at injection site: presence of pruritis at the infusion site without any symptom of inflammation or erythema and/or infection.
Isolated pain at injection site: presence of pain at the infusion site without any symptom of inflammation or erythema and/or infection.
Time Interval Between Infusion Set Changes: All Changes
Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).
"All changes" include all the changes whatever the reason such as routine or requested by occurrence of events.
Time Interval Between Infusion Set Changes in Routine
Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).
Changes in routine correspond to interval between changes according to patient use.
Glycosylated Hemoglobin: HbA1c
Glycolysated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow-up in diabetic patients. This parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7%
Total Daily Basal Insulin Infusion
dose of the basal insulin regimen administered throughout the 24-hour period
Total Daily Bolus Insulin Dose
dose of every increment administered for example before meals
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00607087
Brief Title
Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus
Acronym
PUMP
Official Title
Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Sanofi
4. Oversight
5. Study Description
Brief Summary
Primary objective: To demonstrate the superiority of insulin glulisine over insulin aspart and insulin lispro administered by external pump in term of unexplained hyperglycemia and/or infusion set occlusion.
Main Secondary objectives:
To compare insulin glulisine, insulin aspart and insulin lispro on:
Unexplained hyperglycemia
Infusion set occlusion
Hypoglycemic episodes,7-point blood glucose profiles
Episodes of significant ketosis and/or risk level for impending diabetic ketoacidosis
Time to change the infusion set
HbA1c (Glycosylated hemoglobin)
Overall safety: incidence of adverse events
Detailed Description
The maximal duration of the study participation for patients was 41 weeks and one day, split in:
a 2-week screening period,
a 39-week treatment period: 3 treatment periods of 13 weeks with a crossover alternative regimen, including a dose adjustment period of 1 week at the beginning of each period (sequence1: insulin glulisine, then insulin aspart, then insulin lispro; sequence2: insulin aspart, then insulin lispro, then insulin glulisine; sequence 3: insulin lispro, then insulin glulisine, then insulin aspart)
and a follow-up period of 24 hours.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
289 (Actual)
8. Arms, Groups, and Interventions
Arm Title
sequence 1
Arm Type
Experimental
Arm Description
sequence 1: insulin glulisine / insulin aspart / insulin lispro.
Arm Title
Sequence 2
Arm Type
Experimental
Arm Description
Sequence 2: insulin aspart / insulin lispro / insulin glulisine
Arm Title
Sequence 3
Arm Type
Experimental
Arm Description
Sequence 3: insulin lispro / insulin glulisine / insulin aspart
Intervention Type
Drug
Intervention Name(s)
Insulin glulisine
Intervention Description
100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump
Intervention Type
Drug
Intervention Name(s)
Insulin lispro
Intervention Description
100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump
Intervention Type
Drug
Intervention Name(s)
Insulin aspart
Intervention Description
100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump
Primary Outcome Measure Information:
Title
Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
Description
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Time Frame
over 13 weeks of each treatment period
Secondary Outcome Measure Information:
Title
Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
Description
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Time Frame
over 13 weeks of each treatment period
Title
Percentage of Patients With at Least One Unexplained Hyperglycemia
Description
Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.
Time Frame
over 13 weeks of each treatment period
Title
Monthly Rate of Unexplained Hyperglycemia
Time Frame
over 13 weeks of each treatment period
Title
Percentage of Patients With at Least One Confirmed Infusion Set Occlusion
Description
Pump infusion set occlusion defined by at least one of the following items:
pump occlusion alarm,
patient observation of an occlusion, spontaneously or because of elevated blood glucose value.
Time Frame
over 13 weeks of each treatment period
Title
Monthly Rate of Confirmed Infusion Set Occlusion
Time Frame
over 13 weeks of each treatment period
Title
Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
Description
Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).
Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l
Time Frame
over 13 weeks of each treatment period
Title
Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
Description
Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).
Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l
Time Frame
over 13 weeks of each treatment period
Title
Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year
Description
Symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration.
Time Frame
over 13 weeks of each treatment period
Title
Rate of Severe Symptomatic Hypoglycemia Per Patient-year
Description
Severe symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia in which the patient required assistance of another person and one of the following:
the event was associated with a measured blood glucose level below 36 mg/dL
or event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.
Time Frame
over 13 weeks of each treatment period
Title
Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year
Description
Nocturnal Symptomatic hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration which occurs while the patient is asleep, after bedtime and before getting up in the morning.
Time Frame
over 13 weeks of each treatment period
Title
Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site
Description
Infection: local reaction at the infusion site requiring local or systemic antibiotherapy, or local drainage as per Investigator judgment.
Site inflammation or erythema: local reaction at the infusion site with no need for local or systemic antibiotherapy as per Investigator judgment.
Pruritis at injection site: presence of pruritis at the infusion site without any symptom of inflammation or erythema and/or infection.
Isolated pain at injection site: presence of pain at the infusion site without any symptom of inflammation or erythema and/or infection.
Time Frame
over 13 weeks of each treatment period
Title
Time Interval Between Infusion Set Changes: All Changes
Description
Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).
"All changes" include all the changes whatever the reason such as routine or requested by occurrence of events.
Time Frame
over 13 weeks of each treatment period
Title
Time Interval Between Infusion Set Changes in Routine
Description
Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).
Changes in routine correspond to interval between changes according to patient use.
Time Frame
over 13 weeks of each treatment period
Title
Glycosylated Hemoglobin: HbA1c
Description
Glycolysated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow-up in diabetic patients. This parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7%
Time Frame
over 13 weeks of each treatment period
Title
Total Daily Basal Insulin Infusion
Description
dose of the basal insulin regimen administered throughout the 24-hour period
Time Frame
over 13 weeks of each treatment period
Title
Total Daily Bolus Insulin Dose
Description
dose of every increment administered for example before meals
Time Frame
over 13 weeks of each treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 1 diabetic subjects
Treated with insulin for at least 2 years and by CSII for at least 6 months
Using the same insulin (insulin glulisine, insulin aspart or insulin lispro) in CSII for at least 3 months with the same external pump compatible with the 3 short acting insulin analogues used in the study
Using the same type of infusion set (catheter and cannula) for at least 3 months
Performing at least 3 blood glucose controls per day
HbA1c < 8.5%
Body mass index (BMI) < 35 kg/m²
Ability and willingness to perform blood glucose and ketone monitoring using the Sponsor-provided combined glucose and ketone meter and patient diary at home
Exclusion Criteria:
Diabetes other than Type 1
Total daily dose of insulin greater than 90 U/day
Using an insulin pump requiring pre-filled cartridges
History of infection at infusion site requiring a drainage in the last 3 months
History of severe episodes of ketosis requiring hospitalization in the last 6 months
Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study. An ophthalmoscopic examination should have been performed in the 2 years prior to study entry
Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method) or breastfeeding
Treatment with systemic corticosteroids or medication known to influence insulin sensitivity in the 3 months prior to visit 1
Treatment with antidiabetic drug other than insulin in the 3 months prior to visit 1
Likelihood of requiring treatments during the study which are not permitted
Treatment with an investigational product in the 30 days prior to visit 1
History of sensitivity to the study drugs or to drugs with a similar chemical structure
Presence of any condition (medical, including clinically significant abnormal laboratory test, psychological, social or geographical) actual or anticipated that the Investigator feels would compromise the patient safety or limit his/her successful participation in the study
Night shift workers
Impaired renal function as shown by serum creatinine ≥1.5 mg/dL (133 μmol/L) or ≥1.4 mg/dL (124 μmol/L) in men and women, respectively
Impaired hepatic function as shown by Alanine aminotransferase (ALT) and/or Aspart aminotransferase (AST) greater than three times the upper limit of normal range)
Alcohol or drug abuse in the last year
Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Affairs
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Macquarie Park
Country
Australia
Facility Name
Sanofi-Aventis Administrative Office
City
Vienna
Country
Austria
Facility Name
Sanofi-Aventis Administrative Office
City
Paris
Country
France
Facility Name
Sanofi-Aventis Administrative Office
City
Budapest
Country
Hungary
Facility Name
Sanofi-Aventis Administrative Office
City
Natanya
Country
Israel
Facility Name
Sanofi-Aventis Administrative Office
City
Milan
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
PE Gouda
Country
Netherlands
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Administrative Office
City
Guildford Surrey
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
21457066
Citation
van Bon AC, Bode BW, Sert-Langeron C, DeVries JH, Charpentier G. Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial. Diabetes Technol Ther. 2011 Jun;13(6):607-14. doi: 10.1089/dia.2010.0224. Epub 2011 Apr 2.
Results Reference
derived
Learn more about this trial
Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus
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