Diabetes Mellitus, Type 1
Conditions
Keywords
Type 1 diabetes
Brief summary
The primary objective of this study is to evaluate whether the patients with Type 1 diabetes mellitus in sub-optimal glycemic control can achieve better glycemic control by using the Medtronic MiniMed Paradigm® REAL-Time Pump System with continuous glucose monitoring versus the Medtronic MiniMed Paradigm® REAL-Time Pump alone with Self Monitoring Blood Glucose (SMBG).Our null hypothesis is there is a 0% reduction in HbA1c from baseline compared to control group, after 6 months of treatment.
Interventions
DEVICEinsulin pump with continuous glucose sensing (Paradigm Real-Time Insulin Pump System)
6 months of pump plus continuous glucose sensing in conjunction to SMBG
DEVICEinsulin pump and blinded continuous glucose sensing (Paradigm Real-Time insulin pump)
insulin pump with smbg to be worn for 6 months. 15 days in each 6 week period blinded continuous glucose sensing will be conducted.
Sponsors
Medtronic Diabetes
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Type 1 diabetes mellitus diagnosed for at least 12 months prior to signature of informed consent, * Sub-optimal glycemic control (7.5%\<HbA1c\<9.5%). * Patient treated by continuous subcutaneous insulin infusion (CSII) for at least 6 months prior signature of informed consent. * Patient treated within the practice of the investigator's center at least 6 months prior signature of informed consent. * Patient has no preliminary experience with the sensor function of the Paradigm REAL-Time or the Guardian® REAL-Time for the 4 months prior signature of informed consent.
Exclusion criteria
* Existing pregnancy or intention to conceive (as assessed by investigator). * Hearing or vision impairment so that glucose display and alarms cannot be recognized. * Three or more incidents in the last 12 months of severe hypoglycaemia with documented Blood Glucose below 50mg/dL (if possible), resulting in unconsciousness, hospitalisation or third party assistance, where recovery follows treatment with glucose or glucagon or similar. * History of hypoglycemic unawareness as assessed by the investigator. * Alcohol or drug abuse, other than nicotine. * Documented cutaneous allergy or disease (allergy to sensor or components of the sensor, psoriasis, staphylococcus, exanthema etc.). * Any documented concomitant chronic disease known to affect diabetes control (e.g. altered renal function, active cancer undergoing treatment, Crohn's disease, ulcerative colitis, Mb Addison disease) or any concomitant pharmacological treatment that might modify glycemic values (e.g chronic corticosteroid therapy), eating disorders and morbid obesity (defined as adults : Body Mass Index \>35 and children Body Mass Index \> 2 standard deviations. for age) as assessed by the investigator. * Any other medical, social or psychological condition that, in the investigator's opinion, makes the patient unable to comply with the study protocol and all study procedures. * For pediatric subjects: does not have a reliable support person. * Plans to travel for extended periods (3+ weeks) where the devices cannot be supplied or replaced and/or medical support is limited (eg. exotic countries, remote places). * Participation in another clinical study, on-going or completed less than 3 months prior to signature of Patient Informed Consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c at 6 Month | 6 months | The end of period difference in HbA1c after 6 months of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe Hypoglycemia Events | 6 months | — |
| Daily Min Spent in Euglycaemia (3.9-10.0 mmol/l) | 6 months | — |
| Glycemic Variability | 6 months | 24 h SD of glucose values (mg/dl) |
| Pediatric Quality of Life Inventory (Vers 4.0; PedsQL) | 6 months | This questionnaire is a validated assessment of health-related quality of life in children developed by J.W. Varni, (1998). Scores are transformed on a scale from 0 to 100. higher values represent a better outcome |
| Diabetic Ketoacidosis Events | 6 months | A diabetic ketoacidosis event (DKE) is defined as a hyperglycemia (blood glucose \>250 mg/dL) with either low serum bicarbonate (\<15 mEq/L) and/or low pH (\<7.3) and either ketonemia or ketonuria and requiring treatment within a health-care facility. |
| Postprandial Glycaemia | 6 months | Breakfast Postprandial glycaemia |
Countries
Austria, Denmark, Italy, Luxembourg, Netherlands, Slovenia, Spain
Participant flow
Pre-assignment details
Cross-over design 1 month run-in before randomization 4 month wash out period
Participants by arm
| Arm | Count |
|---|---|
| Off/On 6 month-Period Off: Continuous Subcutaneous Insulin Infusion (CSII) and Self Monitoring Blood Glucose \[Device: Paradigm® Real-Time pump with Sensor Off feature\]
4 month wash out period
6 month-Period On: Continuous Subcutaneous Insulin Infusion (CSII) + personal continuous glucose monitoring (personal CGM) \[Device: Paradigm® Real-Time pump with Sensor On feature continuously\] | 76 |
| On/Off 6 month-Period On: Continuous Subcutaneous Insulin Infusion (CSII) + personal continuous glucose monitoring (personal CGM) \[Device: Paradigm® Real-Time pump with Sensor On feature continuously\]
4 month wash out period
6 month-Period Off: Continuous Subcutaneous Insulin Infusion (CSII) and Self Monitoring Blood Glucose \[Device: Paradigm® Real-Time pump with Sensor Off feature\] | 77 |
| Total | 153 |
Baseline characteristics
| Characteristic | Off/On | On/Off | Total |
|---|---|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 17 | 28 years STANDARD_DEVIATION 16 | 28 years STANDARD_DEVIATION 17 |
| Sex: Female, Male Female | 39 Participants | 35 Participants | 74 Participants |
| Sex: Female, Male Male | 37 Participants | 42 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 153 |
| other Total, other adverse events | 64 / 153 | 52 / 153 |
| serious Total, serious adverse events | 5 / 153 | 6 / 153 |
Outcome results
Primary
HbA1c at 6 Month
The end of period difference in HbA1c after 6 months of treatment
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sensor Off Arm | HbA1c at 6 Month | 8.47 percentage of glycosylated hemoglobin | Standard Deviation 0.96 |
| Sensor ON Arm | HbA1c at 6 Month | 8.04 percentage of glycosylated hemoglobin | Standard Deviation 0.87 |
p-value: <0.0001ANCOVA
Secondary
Daily Min Spent in Euglycaemia (3.9-10.0 mmol/l)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sensor Off Arm | Daily Min Spent in Euglycaemia (3.9-10.0 mmol/l) | 669 minutes | Standard Deviation 208 |
| Sensor ON Arm | Daily Min Spent in Euglycaemia (3.9-10.0 mmol/l) | 774 minutes | Standard Deviation 232 |
Secondary
Diabetic Ketoacidosis Events
A diabetic ketoacidosis event (DKE) is defined as a hyperglycemia (blood glucose \>250 mg/dL) with either low serum bicarbonate (\<15 mEq/L) and/or low pH (\<7.3) and either ketonemia or ketonuria and requiring treatment within a health-care facility.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sensor Off Arm | Diabetic Ketoacidosis Events | 3 Participants |
| Sensor ON Arm | Diabetic Ketoacidosis Events | 2 Participants |
Secondary
Glycemic Variability
24 h SD of glucose values (mg/dl)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sensor Off Arm | Glycemic Variability | 77.16 mg/dl | Standard Deviation 21.43 |
| Sensor ON Arm | Glycemic Variability | 71.58 mg/dl | Standard Deviation 20.2 |
Secondary
Number of Severe Hypoglycemia Events
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sensor Off Arm | Number of Severe Hypoglycemia Events | 2 participants |
| Sensor ON Arm | Number of Severe Hypoglycemia Events | 4 participants |
Secondary
Pediatric Quality of Life Inventory (Vers 4.0; PedsQL)
This questionnaire is a validated assessment of health-related quality of life in children developed by J.W. Varni, (1998). Scores are transformed on a scale from 0 to 100. higher values represent a better outcome
Time frame: 6 months
Population: In total 72 children took part in the clinical trial: 8 young children (6-7 years), 26 children (8-12 years) and 38 teenagers (13-17 years). Arms/Groups are reported on a per intervention basis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sensor Off Arm | Pediatric Quality of Life Inventory (Vers 4.0; PedsQL) | 85.11 units on a scale | Standard Deviation 9.49 |
| Sensor ON Arm | Pediatric Quality of Life Inventory (Vers 4.0; PedsQL) | 84.75 units on a scale | Standard Deviation 10.41 |
Secondary
Postprandial Glycaemia
Breakfast Postprandial glycaemia
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sensor Off Arm | Postprandial Glycaemia | 157.7 mg/dl | Standard Deviation 24.5 |
| Sensor ON Arm | Postprandial Glycaemia | 160.4 mg/dl | Standard Deviation 31.3 |