Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus, MDI, pump therapy
Brief summary
The purpose of this study is to evaluate the comparative effectiveness of insulin pump therapy versus multiple daily injections in insulin-taking type 2 Diabetes Mellitus who are sub optimally controlled with multiple daily injections (MDI).
Detailed description
The type of study is interventional post-market release. All the devices under investigation have CE mark, and are used within intended use. This study has been designed to be prospective randomized controlled with a single-arm cross-over in the continuation phase. Four hundred type 2 Multiple Daily Injections (MDI) treated patients will undergo a screening (run-in) phase of 8 weeks. The aim of the screening phase is to eliminate the study effect that might result in a decrease of HbA1c and to make sure that patients, who are failing current MDI therapy, are selected. After this screening phase, eligible patients will be randomised to receive either Continuous Subcutaneous Insulin Infusion (CSII) treatment or continue MDI treatment. The study phase is a 6-months phase with 2-arms parallel design.
Interventions
DEVICEInsulin Pump (Medtronic Minimed Paradigm® VEO)
The pump delivers insulin as specified by the patient
Sponsors
Medtronic Diabetes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
at screening: 1. Diagnosed with type 2 DM, as per Investigator discretion 2. HbA1c (DCCT-standard) must be ≥ 8.0% and ≤12% as evidenced by central lab value taken at screening 3. Insulin resistance defined as required daily dose between 0.5-1.8 U/Kg or a maximum of 220 units of insulin per day 4. Aged 30 to 75 years old (inclusive) 5. On MDI regimen (basal/bolus regimen with long-acting insulin and rapid acting analogs) defined as ≥ 3 injections per day for at least 3 months prior signing the informed consent 6. Ability to comply with technology, according to Investigator's judgment 7. Patients must be willing to undergo all study procedures 8. Female patients of child-bearing potential must be using adequate contraception means as assessed by Investigator at randomisation: 1. Diagnosed with type 2 DM, as per Investigator discretion 2. HbA1c (DCCT-standard) must be ≥ 8.0% and ≤12% as evidenced by central lab value 3. Insulin resistance defined as required daily dose between 0.7-1.8 U/Kg or a maximum of 220 units of insulin per day 4. On MDI (basal/bolus regimen with long-acting insulin and rapid acting analogs) defined as ≥ 3 injections per day 5. Ability to comply with technology, according to Investigator's judgment 6. ≥ 2.5 SMBG per day on average, as reported in Carelink clinical during the run-in phase. 7. Patients must be willing to undergo all study procedures 8. Female patients of child-bearing potential must be using adequate contraception means as assessed by Investigator
Exclusion criteria
: 1. Subject has a history (≥ 2 events) of hypoglycemic seizure or hypoglycemic coma within the last 6 months 2. Subject is pregnant as assessed by a pregnancy test with central laboratory, or plans to become pregnant during the course of the study 3. Participation in another interventional clinical study, on-going or completed less than 3 months prior to signature of Patient Informed Consent. 4. Subject has proliferative retinopathy or sight threatening maculopathy 5. Subject has * an acute coronary syndrome (myocardial infarction or unstable angina) within 12 months OR * coronary artery revascularization by bypass surgery or stenting within 3 months OR * a transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 3 months OR * hospitalization for heart failure within 3 months or current New York Functional Class III or IV OR * current 2nd or 3rd degree heart block OR * symptomatic ventricular rhythm disturbances OR * thromboembolic disease within the last 3 months OR * 2nd degree Mobitz type II or 3rd degree heart block 6. Subject with renal impairment expressed as estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula \< 30 ml/min as demonstrated by the screening central laboratory value at the time of enrollment 7. Subject has taken oral or injectable steroids within the last 30 days 8. Systolic blood pressure on screening visit is \> 180 mmHg 9. Diastolic blood pressure on screening visit is \> 110 mmHg 10. Any other disease (eg active cancer under treatment) or condition including abnormalities found on the screening tests, that in the opinion of the Investigator, may preclude him/her from participating in the study 11. Taking any medication prescribed for weight loss 12. Alcohol or drug abuse, other than nicotine, at the investigator's discretion 13. Use of a GLP-1 agonist or pramlintide (Symlin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Between Group Difference in HbA1c When Comparing CSII to MDI | baseline and 6 months | To evaluate change in glycemic control (HbA1c) after 6 months of insulin pump therapy in patients with type 2 DM, as compared to patients on MDI therapy over the same time period. Change in A1c = A1c at 6 month - A1c at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Severe Hypoglycemia Incidence | 6 months | Severe hypoglycemia incidence during the study |
| Change in Glycemic Variability - AUC in Hyper (≥180mg/dL) | 6 months | Glycemic parameters calculated from blinded CGM data: change in AUC (Area Under the Curve) in hyper- (≥180mg/dL), among subjects with available AUC results. Change in hyper AUC = hyper AUC at 6 month - hyper AUC at baseline |
| Change in Glycemic Variability - AUC in Hypo (≤70mg/dL) | 6 months | Glycemic parameters calculated from blinded CGM data: change in AUC (Area Under the Curve) in hypo- (≤70mg/dL), among subjects with available AUC results. Change in hypo AUC = hypo AUC at 6 month - hypo AUC at baseline |
| Change in Body Weight | 6 months | Change in body weight from randomization to the end of study. Change in body weight = weight at 6 month - weight at baseline, among subjects with available body weight |
| Safety - Diabetic Ketoacidosis Incidence | 6 Months | Diabetic Ketoacidosis incidence during the study |
| Quality of Life and Treatment Satisfaction - Results From Diabetes Treatment Satisfaction Questionnaire (DTSQ) | 6 months | Subjects were asked to complete the Diabetes Treatment Satisfaction Questionnaire (DTSQs). Treatment satisfaction is measured by means of the DTSQs, status version (DTSQs, Bradley, 1990). It consists of a six-item scale assessing treatment satisfaction (TS) and two items assessing perceived frequency of hyperglycaemia and hypoglycaemia. The DTSQs items are scored on a scale from 0 to 6. The scale total is computed by adding the six items 1, 4, 5, 6, 7, and 8, to produce the Treatment Satisfaction scale total, which has a min of 0 and a max of 36. Higher score at 6 month compared to baseline represents a better outcome. Change in treatment satisfaction = score at 6 month - score at baseline, among subjects with available satisfaction scores |
Countries
Austria, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, North Macedonia, Serbia, South Africa, Spain, United States
Participant flow
Recruitment details
36 hospitals, tertiary care centres, and referal centres participated: eight in Canada, 23 in Europe and Israel, two in South Africa, and three in the USA. The study started in December 2010, and the fi nal data collection date for the primary outcome measure was in February 2014
Participants by arm
| Arm | Count |
|---|---|
| Insulin Pump Treatment Patients will get an insulin pump
Insulin Pump (Medtronic Minimed Paradigm® VEO): The pump delivers insulin as specified by the patient | 168 |
| Insulin Treatment With MDI patients treated with Multiple Daily Injections (MDI); basal/bolus therapy with rapid- and long-acting analogs with at least 3 injections per day | 163 |
| Total | 331 |
Baseline characteristics
| Characteristic | Insulin Treatment With MDI | Insulin Pump Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 163 Participants | 168 Participants | 331 Participants |
| Age, Continuous | 56.4 years STANDARD_DEVIATION 9.5 | 55.5 years STANDARD_DEVIATION 9.7 | 56.0 years STANDARD_DEVIATION 9.6 |
| HbA1c | 9.0 % of glycosylated hemoglobin STANDARD_DEVIATION 0.76 | 9.0 % of glycosylated hemoglobin STANDARD_DEVIATION 0.75 | 9.0 % of glycosylated hemoglobin STANDARD_DEVIATION 0.75 |
| Sex: Female, Male Female | 77 Participants | 74 Participants | 151 Participants |
| Sex: Female, Male Male | 86 Participants | 94 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 168 | 0 / 163 |
| other Total, other adverse events | 108 / 168 | 99 / 163 |
| serious Total, serious adverse events | 13 / 168 | 10 / 163 |
Outcome results
Primary
Between Group Difference in HbA1c When Comparing CSII to MDI
To evaluate change in glycemic control (HbA1c) after 6 months of insulin pump therapy in patients with type 2 DM, as compared to patients on MDI therapy over the same time period. Change in A1c = A1c at 6 month - A1c at baseline
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Pump Treatment | Between Group Difference in HbA1c When Comparing CSII to MDI | -1.1 Change in % HbA1c | Standard Deviation 1.2 |
| Insulin Treatment With MDI | Between Group Difference in HbA1c When Comparing CSII to MDI | -0.4 Change in % HbA1c | Standard Deviation 1.1 |
Secondary
Change in Body Weight
Change in body weight from randomization to the end of study. Change in body weight = weight at 6 month - weight at baseline, among subjects with available body weight
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Pump Treatment | Change in Body Weight | 1.52 kg | Standard Deviation 3.53 |
| Insulin Treatment With MDI | Change in Body Weight | 1.12 kg | Standard Deviation 3.62 |
Secondary
Change in Glycemic Variability - AUC in Hyper (≥180mg/dL)
Glycemic parameters calculated from blinded CGM data: change in AUC (Area Under the Curve) in hyper- (≥180mg/dL), among subjects with available AUC results. Change in hyper AUC = hyper AUC at 6 month - hyper AUC at baseline
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Pump Treatment | Change in Glycemic Variability - AUC in Hyper (≥180mg/dL) | -11 mg/dL/min | Standard Deviation 26.3 |
| Insulin Treatment With MDI | Change in Glycemic Variability - AUC in Hyper (≥180mg/dL) | -2.6 mg/dL/min | Standard Deviation 17.4 |
Secondary
Change in Glycemic Variability - AUC in Hypo (≤70mg/dL)
Glycemic parameters calculated from blinded CGM data: change in AUC (Area Under the Curve) in hypo- (≤70mg/dL), among subjects with available AUC results. Change in hypo AUC = hypo AUC at 6 month - hypo AUC at baseline
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Pump Treatment | Change in Glycemic Variability - AUC in Hypo (≤70mg/dL) | 0 mg/dL/min | Standard Deviation 0.6 |
| Insulin Treatment With MDI | Change in Glycemic Variability - AUC in Hypo (≤70mg/dL) | -0.1 mg/dL/min | Standard Deviation 0.9 |
Secondary
Quality of Life and Treatment Satisfaction - Results From Diabetes Treatment Satisfaction Questionnaire (DTSQ)
Subjects were asked to complete the Diabetes Treatment Satisfaction Questionnaire (DTSQs). Treatment satisfaction is measured by means of the DTSQs, status version (DTSQs, Bradley, 1990). It consists of a six-item scale assessing treatment satisfaction (TS) and two items assessing perceived frequency of hyperglycaemia and hypoglycaemia. The DTSQs items are scored on a scale from 0 to 6. The scale total is computed by adding the six items 1, 4, 5, 6, 7, and 8, to produce the Treatment Satisfaction scale total, which has a min of 0 and a max of 36. Higher score at 6 month compared to baseline represents a better outcome. Change in treatment satisfaction = score at 6 month - score at baseline, among subjects with available satisfaction scores
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Pump Treatment | Quality of Life and Treatment Satisfaction - Results From Diabetes Treatment Satisfaction Questionnaire (DTSQ) | 4.75 score | Standard Deviation 6.9 |
| Insulin Treatment With MDI | Quality of Life and Treatment Satisfaction - Results From Diabetes Treatment Satisfaction Questionnaire (DTSQ) | -0.26 score | Standard Deviation 6.9 |
Secondary
Safety - Diabetic Ketoacidosis Incidence
Diabetic Ketoacidosis incidence during the study
Time frame: 6 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Pump Treatment | Safety - Diabetic Ketoacidosis Incidence | 0 Participants |
| Insulin Treatment With MDI | Safety - Diabetic Ketoacidosis Incidence | 0 Participants |
Secondary
Safety - Severe Hypoglycemia Incidence
Severe hypoglycemia incidence during the study
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Pump Treatment | Safety - Severe Hypoglycemia Incidence | 0 Participants |
| Insulin Treatment With MDI | Safety - Severe Hypoglycemia Incidence | 1 Participants |