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

OpT2mise Glucose Control in Type 2 DM With Insulin Pump Therapy

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Device: Insulin Pump (Medtronic Minimed Paradigm® VEO)

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.

• Study Type: Interventional
• Enrollment (Actual): 331
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1130
    • City hopital Vienna-Hieting
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 0M3
      • Clinical Professor Department of Medicine University of Calgary
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W5
      • Endocrinologist, 202-301 Columbia Street East
    • Vancouver, British Columbia, Canada, V6E 1M7
      • 416-1033 Davie St
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Health Science Centre
  • Ontario
    • Oakville, Ontario, Canada, L6H 3P1
      • LMC Endocrinology Centre
    • Smiths' Falls, Ontario, Canada, K7A 4W8
      • Canadian Centre for Research on Diabetes
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hsopital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University, McGill Nutrition and Food Science Centre
• France
  • Caen, France, 14033
    • CHU côte de Nacre
  • Marseille, France, 13274
    • CHU - Ste Marguerite
  • Montpellier, France, 34295
    • Hôpital Lapeyronie
  • Nancy, France, 54500
    • Chu de Nancy
  • Strasbourg, France, 67091
    • CHU Strasbourg
  • Toulouse, France, 31059
    • CHU Toulouse Rangueil
• Germany
  • Bad Heilbrunn, Germany, 83670
    • Fachklinik Bad Heilbrunn
  • Münster, Germany, 48145
    • Zentrum für Diabetes und Gefäßerkrankungen
• Hungary
  • Budapest, Hungary, 1076
    • Péterfy Hospital and Emergency Center Diabetes Outpatient Clinic
• Israel
  • Beer-Sheva, Israel, 84105
    • Soroka University Medical Center
  • Jerusalem, Israel, 93106
    • Diabetic Clinic
  • Tel Hashomer - Ramat Gan, Israel, 5262
    • Chaim Sheba Medical center Endocrinology unit
  • Zerifin, Israel, 70300
    • Assaf- Harofeh Medical Center
• Italy
  • Bari, Italy, 70124
    • Università degli Studi di Bari - Policlinico Universitario
  • Perugia, Italy, 06132
    • Università di Perugia - Ospedale S.M. Della Misericordia
  • Roma, Italy, 00161
    • University La Sapienza - Policlinico
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • University Clinic of Endocrinology
• Netherlands
  • Capelle A/d IJssel, Netherlands, 2906
    • IJsselland Ziekenhuis Poli Interne geneeskunde
  • Eindhoven, Netherlands, 5600
    • Maxima Medisch Centrum
  • Hoogeveen, Netherlands, 7900
    • Bethesda Diabetes Research Center
• Serbia
  • Belgrade, Serbia, 11 000
    • Clinic for Endocrinology, Diabetes and Metabolic Diseases
• South Africa
  • Johannesburg, South Africa, 2198
    • Centre for Diabetes and Endocrinology
  • Port Elizabeth, South Africa, 6001
    • Dr.Garcjan Podgorski
• Spain
  • Barcelona, Spain, 08036
    • ICMDM Hospital Clínic i Universitari
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Pump Treatment; Patients will get an insulin pump	Device: Insulin Pump (Medtronic Minimed Paradigm® VEO); The pump delivers insulin as specified by the patient; Other Names: Medtronic MiniMed Paradigm® VEO system (MMT-554/754
No Intervention: 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

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

Collaborators and Investigators

• Sponsor: Medtronic Diabetes
• Investigators: Principal Investigator: Ohad Cohen, MD, Chaim Sheba Medical Center, Tel Hashomer, Israel; Principal Investigator: Ignacio Conget, MD, ICMDM Hospital Clínic i, Barcelona, Spain; Principal Investigator: Yves Reznic, MD, CHU Côte de Nacre, France; Principal Investigator: Ronnie Aronson, MD, FRCPC, FACE LMC Endocrinology Centres, Canada

Publications and helpful links

General Publications

• Chlup R, Runzis S, Castaneda J, Lee SW, Nguyen X, Cohen O. Complex Assessment of Metabolic Effectiveness of Insulin Pump Therapy in Patients with Type 2 Diabetes Beyond HbA1c Reduction. Diabetes Technol Ther. 2018 Feb;20(2):153-159. doi: 10.1089/dia.2017.0283. Epub 2017 Dec 7.
• Metzger M, Castaneda J, Reznik Y, Giorgino F, Conget I, Aronson R, de Portu S, Runzis S, Lee SW, Cohen O. Factors associated with improved glycemic control following continuous subcutaneous insulin infusion therapy in patients with type 2 diabetes uncontrolled with bolus-basal insulin regimens: An analysis from the OpT2mise randomized trial. Diabetes Obes Metab. 2017 Oct;19(10):1490-1494. doi: 10.1111/dom.12960. Epub 2017 Jul 25.
• Reznik Y, Cohen O, Aronson R, Conget I, Runzis S, Castaneda J, Lee SW; OpT2mise Study Group. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial. Lancet. 2014 Oct 4;384(9950):1265-72. doi: 10.1016/S0140-6736(14)61037-0. Epub 2014 Jul 2.

Helpful Links

• Publication of primary endpoints in the Lancet

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 13, 2010
• First Posted (Estimate): August 16, 2010

Study Record Updates

• Last Update Posted (Actual): March 12, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; MDI; pump therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: EUR05 / CEP234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No