OpT2mise Glucose Control in Type 2 Diabetes Mellitus (DM) With Insulin Pump Therapy

Study Overview
=================
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.

Official Title
-----------------
OpT2mise Glucose Control in Type 2 DM With Insulin Pump Therapy

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Device: Insulin Pump (Medtronic Minimed Paradigm® VEO)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria at screening: Diagnosed with type 2 DM, as per Investigator discretion HbA1c (DCCT-standard) must be ≥ 8.0% and ≤12% as evidenced by central lab value taken at screening Insulin resistance defined as required daily dose between 0.5-1.8 U/Kg or a maximum of 220 units of insulin per day Aged 30 to 75 years old (inclusive) 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 Ability to comply with technology, according to Investigator's judgment Patients must be willing to undergo all study procedures Female patients of child-bearing potential must be using adequate contraception means as assessed by Investigator at randomisation: Diagnosed with type 2 DM, as per Investigator discretion HbA1c (DCCT-standard) must be ≥ 8.0% and ≤12% as evidenced by central lab value Insulin resistance defined as required daily dose between 0.7-1.8 U/Kg or a maximum of 220 units of insulin per day On MDI (basal/bolus regimen with long-acting insulin and rapid acting analogs) defined as ≥ 3 injections per day Ability to comply with technology, according to Investigator's judgment ≥ 2.5 SMBG per day on average, as reported in Carelink clinical during the run-in phase. Patients must be willing to undergo all study procedures Female patients of child-bearing potential must be using adequate contraception means as assessed by Investigator Exclusion Criteria : Subject has a history (≥ 2 events) of hypoglycemic seizure or hypoglycemic coma within the last 6 months Subject is pregnant as assessed by a pregnancy test with central laboratory, or plans to become pregnant during the course of the study Participation in another interventional clinical study, on-going or completed less than 3 months prior to signature of Patient Informed Consent. Subject has proliferative retinopathy or sight threatening maculopathy 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 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 Subject has taken oral or injectable steroids within the last 30 days Systolic blood pressure on screening visit is > 180 mmHg Diastolic blood pressure on screening visit is > 110 mmHg 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 Taking any medication prescribed for weight loss Alcohol or drug abuse, other than nicotine, at the investigator's discretion Use of a GLP-1 agonist or pramlintide (Symlin)

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Pump Treatment<br>Patients will get an insulin pump | Device: Insulin Pump (Medtronic Minimed Paradigm® VEO)<br>* The pump delivers insulin as specified by the patient<br>* Other names: Medtronic MiniMed Paradigm® VEO system (MMT-554/754;|
| No Intervention: Insulin treatment with MDI<br>patients treated with Multiple Daily Injections (MDI); basal/bolus therapy with rapid- and long-acting analogs with at least 3 injections per day | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months | 
| Safety - Severe Hypoglycemia Incidence | Severe hypoglycemia incidence during the study | 6 months | 
| 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 | 6 months | 
| 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 | 6 months | 
| 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 | 6 months | 
| Safety - Diabetic Ketoacidosis Incidence | Diabetic Ketoacidosis incidence during the study | 6 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes Mellitus, MDI, pump therapy