Improving Glycaemic Control in Malaysian Patients With Type 2 Diabetes Mellitus With Insulin Pump Therapy

The purpose of this study is to evaluate the comparative efficacy of insulin pump therapy versus multiple daily injections in insulin-taking type 2 diabetes mellitus who are sub-optimally controlled with premixed insulin regimen. This research is necessary because many patients with type 2 diabetes mellitus do not meet their glucose targets.

In advanced Type 2 diabetes mellitus, many patients develop worsening diabetes control and unable to reach the glucose targets despite intensive insulin regimens.This is further complicated by the risks of low blood sugar and weight gain. These limitations of multiple daily injection treatment show the need for new treatments for this group of patients.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Device: Insulin Pump; Drug: Multiple daily injections of insulin

Detailed Description

This study evaluates between group change in glycemic control (HbA1c) after 6 months of insulin pump therapy in patients with type 2 Diabetes Mellitus, as compared to patients on multiple daily injections (MDI) therapy over the same time period. It also evaluates between group changes in diabetes clinical outcomes after 6 months in patients with type 2 DM. Patient related outcomes will be measured after 6 months of therapy. The primary endpoint will be between group difference in average HbA1c changes from baseline to 6 months, when comparing Continuous Subcutaneous Insulin Infusion (CSII) to MDI.

The secondary end point concerns the safety issues such as severe hypoglycemia incidence: defined as an episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory blood glucose by finger stick of less than 50mg/dL (2.8 mmol/L), (i.e., subject is unable to treat self and requires carbohydrate, glucagon or other resuscitative actions to prevent further clinical deterioration), hospitalizations, Diabetic Ketoacidosis (DKA), an acute metabolic complication of diabetes, characterized by hyperglycemia, hyperketonemia, and metabolic acidosis, within group difference in HbA1c from 6 months to 12 months, change in weight or BMI, change in Lipids : total cholesterol, high density lipoprotein(HDL),low density lipoprotein(LDL),triglyceride, change in blood pressure, Insulin Dosage Changes (Total Daily Dose), Number of self monitoring blood glucose (SMBG)/day, treatment satisfaction: Diabetes Treatment Satisfaction Questionnaire status and change version (DTSQs and DTSQc).

The hypotheses underlying the secondary outcomes : the pump therapy improves glycaemic control whilst utilizing less total daily dose of insulin in comparison to multiple daily injections of insulin. This is associated with parallel improvement in metabolic profiles such as blood pressure and lipids. As for the glucose monitoring, investigators want to evaluate whether there is any difference in the frequency of SMBG/day between the 2 treatment groups. More frequent SMBG monitoring denotes better compliance, motivation and empowerment by the participants to control their diabetes.

• Study Type: Interventional
• Enrollment (Anticipated): 118
• Phase: Phase 4

Contacts and Locations

Study Locations

• Malaysia
  • Wilayah Persekutuan
    • Putrajaya, Wilayah Persekutuan, Malaysia, 62250
      • Recruiting
      • Hospital Putrajaya
      • Contact: Zanariah Hussein, MBBS,MRCP; Phone Number: 0122907136; Email: ppzana@hpj.gov.my
      • Contact: Nurain Mohd Noor, MBBS,MMed; Phone Number: 0122051570; Email: ppnurain@hpj.gov.my
      • Principal Investigator: Noor Rafhati Adyani Abdullah, MBBS,MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

CRITERIA FOR INCLUSION AT SCREENING

1. Diagnosed with type 2 Diabetes Mellitus, as per Investigator diagnosis
2. HbA1c (DCCT-standard) must be ≥ 9.0% and ≤12%
3. Insulin resistance defined as required daily dose up to 1.5u/kg or a maximum of 200 units insulin per day
4. Aged 20 to 75 years old inclusive
5. On premixed regimen (human or analogue insulin) defined as ≥ 2 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

CRITERIA FOR INCLUSION AT RANDOMISATION

1. Diagnosed with type 2 DM, as per Investigator diagnosis
2. HbA1c (DCCT-standard) must be ≥ 9.0% and ≤12%
3. Insulin resistance defined as required daily dose up to 1.5 U/Kg or a maximum of 200 units per day
4. On premixed regimen (human or analogue insulin) defined as ≥ 2 injections per day for at least 3 months prior signing the informed consent
5. Ability to comply with technology, according to Investigator's judgment
6. ≥ 2.5 SMBG per day on average
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:

CRITERIA FOR EXCLUSION (AT SCREENING AND RANDOMISATION)

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
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 the patient 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 Use of a Glucagon Like Peptide-1 agonist or pramlintide (Symlin®). Glucagon Like Peptide-1 slows gastric emptying, thereby decreasing the rate of glucose absorption. Pramlintide (Symlin®) is a commercially available analogue of amylin, a synergistic partner to insulin.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Insulin pump; Medtronic Minimed Paradigm Veo Insulin Pump utilising rapid acting insulin Glulisine or Aspart	Device: Insulin Pump; Medtronic Minimed Paradigm Veo Insulin Pump; Drug: Multiple daily injections of insulin; Multiple daily injections which consist of a single injection of basal insulin(insulin Glargine) and 3 injections of bolus insulin(rapid acting insulin Glulisine or Aspart) before each meal; Other Names: Basal bolus injections of insulin
Active Comparator: Multiple daily injections of insulin; Multiple daily injections consisting of a single basal insulin injection(Glargine) and 3 bolus insulin injections (rapid acting insulin Glulisine or Aspart) before each meal	Device: Insulin Pump; Medtronic Minimed Paradigm Veo Insulin Pump; Drug: Multiple daily injections of insulin; Multiple daily injections which consist of a single injection of basal insulin(insulin Glargine) and 3 injections of bolus insulin(rapid acting insulin Glulisine or Aspart) before each meal; Other Names: Basal bolus injections of insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
between group difference of HbA1c changes from baseline to 6 months	Between group difference in HbA1c changes from baseline to 6 months, when comparing CSII to MDI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within group difference in HbA1c changes from 6 months to 12 months	Within group difference in HbA1c changes from 6 months to 12 months after cross-over from MDI to CSII	1 year
Safety endpoints which are 1) Number of events of severe hypoglycemia 2)Any hospitalizations for hypoglycaemia or hyperglycaemic emergencies 3)Number of events of Diabetic Ketoacidosis (DKA)	Number of events of severe hypoglycemia : defined as an episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory blood glucose by finger stick of less than 50mg/dL (2.8 mmol/L), (i.e., subject is unable to treat self and requires carbohydrate, glucagon or other resuscitative actions to prevent further clinical deterioration); Any hospitalizations for hypoglycaemia or hyperglycaemic emergencies; Number of events of Diabetic Ketoacidosis (DKA), an acute metabolic complication of diabetes, characterized by hyperglycemia, hyperketonemia, and metabolic acidosis	1 year
change in weight (kg)	Between and within group difference in average weight changes when comparing CSII to MDI	1 year
Number of Self Monitoring Blood Glucose (SMBG) per day	Between and within group difference in the number of SMBG per day between CSII and MDI. The data is downloaded using Bayer Glucofacts Deluxe Software from the glucometer during each visit.	1 year
Total Daily Insulin Dosage per day in Unit/day	Between and within group total daily insulin dosage per day in Unit/day between CSII and MDI. The total daily insulin dose per day in the CSII group is downloaded from Medtronic CareLink Therapy Management Software whereas for the MDI group, it is the cumulative dosage of total insulin per day.	1 year
Total Daily Insulin Dosage per body weight in kilograms per day (Unit/kg/day)	Between and within group total daily insulin dosage per day (Outcome 6) divide by body weight in kilograms (Outcome 8) measured as (Unit/kg/day) for each patient,comparing between CSII and MDI	1 year
Body weight in kilograms	Between and within group body weight in kilograms, comparing between CSII and MDI	1 year
Treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire DTSQs	Treatment satisfaction: Diabetes Treatment Satisfaction Questionnaire using DTSQs comparing between CSII and MDI	1 year

Collaborators and Investigators

• Sponsor: Clinical Research Centre, Malaysia
• Collaborators: Medtronic
• Investigators: Principal Investigator: Noor Rafhati Adyani NR Abdullah, MBBS,MRCP, Putrajaya Hospital, Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: April 9, 2017
• First Posted (Actual): April 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2017
• Last Update Submitted That Met QC Criteria: April 9, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: insulin pump; basal bolus insulin
• 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; Insulin, Globin Zinc
• Other Study ID Numbers: NERP14-019

Plan for Individual participant data (IPD)

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