Long Acting Insulin Glargine Titration Web Tool (LTHome) vs Enhanced Usual Therapy of Glargine Titration (INNOVATE)

A 12 Week, Parallel, Open-label, Randomized, Multi-center Study Evaluating Use, Safety and Effectiveness of a Web Based Tool vs. Enhanced Usual Therapy of Glargine Titration in T2DM Patients With a 4 Week Safety Extension

Evaluating patients with type 2 diabetes either starting once daily basal insulin or requiring increased basal titrations in order to compare the LTHome web based tool with the usual standard of practice for insulin glargine dosing adjustment.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: Long-acting insulin glargine titration web tool (LTHome); Other: Diabetes Education

Detailed Description

INNOVATE is a 12 week, parallel, open-label, randomized, multi-center study evaluating use, safety and effectiveness of a web based tool (LTHome) vs. enhanced usual therapy (EUT) of glargine titration in T2DM patients.

The primary objective of this study is to compare the effectiveness LTHome versus EUT of glargine titration in people with T2DM patients on basal insulin not meeting local targets or patients requiring basal initiation. Success will be measured by the percentage of subjects reaching Canadian Diabetes Association (CDA) guideline targets.

The efficacy objective is to demonstrate that the percentage (%) of subjects to reach FPG target by titration of insulin glargine using the LTHome tool with dose adjustment advice is not inferior to the % of subjects to reach FPG target using Enhanced Usual Therapy glargine titration during study participation (LTHome vs. EUT treatments).

The secondary objectives of this study are to assess safety, effectiveness, satisfaction and adherence of LTHome use versus Enhanced Usual Therapy glargine titration.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Diabetes & Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with type 2 diabetes mellitus (T2DM) between 18 and 75 years old (inclusively) with BMI ≤ 45 kg/m2.
• Signed written informed consent

• Patients scheduled to: initiate basal insulin treatment or increase their dose of current basal insulin therapy, independently of study participation, because of :

  • inadequate blood glucose control

• If on basal therapy at screening, must be using a stable dose of insulin glargine x 1 week prior to randomization

• Patients with poor blood glucose control defined by:

  • HbA1c level between > 7% at screening AND
  • mean FPG > 7 mmol/l as determined by most recent self-measured blood glucose in 3 of 7 days prior to randomization
• Patients proficient in computer literacy
• Patient is able and willing to monitor glucose with a home glucose monitor, and consistently record his/her blood glucose and insulin doses in a patient diary/web tool.

Exclusion Criteria:

• Any technical/administrative reason that makes it impossible to include the patient in the study, including closing enrollment due to full enrollment
• Patient who has previously participated in any clinical trial investigating the LTHome algorithm
• Patient who withdraws consent during screening (starting from signed informed consent form)
• Use of systemic steroids in the last 90 days

• Conditions/situations:

  • Patients with short life expectancy (less than 1 year)
  • Type 1 diabetes mellitus
  • Patients with conditions/concomitant diseases making them non-evaluable for the primary efficacy endpoint
  • Clinically significant cardiac disease, retinopathy, hepatic, renal dysfunction or relevant other major diseases as determined by Principal Investigator or designee.
  • Unstable oral antihyperglycemic drugs and/or Glucagon-Like Peptide Receptor (GLP-1R) Agonists therapy during the 4 week period prior to screening
  • Impossibility to meet specific protocol requirements (e.g. ability to perform blood glucose measurements, manage their own insulin glargine administration or deemed unlikely to safely manage insulin dosage on guidance by their HCP)
  • Patient is a primary relative of the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, or other staff or is directly involved in the conduct of the protocol
  • Patients with hypoglycemia unawareness, severe hypoglycemic episode in the last 90 days or hospitalization (for any reason) in the last 30 days
  • Cognitive disorder, dementia or any neurologic disorder, that would affect patient's ability to participate in the study, or patients who have no legal capacity or are under guardianship
• Pregnant or breastfeeding women, or women of child-bearing potential not protected by highly effective method(s) of birth control (as defined in the informed consent form and/or in a local protocol addendum) and who are unwilling or unable to be tested for pregnancy.
• Patients who are using, or need to start using, mealtime (Bolus) insulin during the timeframe of the study.
• Night shift workers

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: LTHome web tool; The long-acting insulin glargine titration web tool (LTHome) will provide insulin glargine titration suggestions based on user inputted blood glucose readings.	Other: Long-acting insulin glargine titration web tool (LTHome); The LTHome study arm will receive insulin glargine titration instructions from the LTHome web-based tool; Other: Diabetes Education; Individual diabetes education, detailed instructions on the use of the blood glucose monitor and unlimited availability of blood glucose monitoring supplies.
Active Comparator: Enhanced Usual Therapy (EUT); The Enhanced Usual Therapy arm will receive insulin glargine titration instructions that are the usual therapy provided by the physician/HCP, in addition to diabetes education.	Other: Diabetes Education; Individual diabetes education, detailed instructions on the use of the blood glucose monitor and unlimited availability of blood glucose monitoring supplies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects reaching fasting plasma glucose (FPG) target	The primary outcome is defined as all of the following; At least 4 out of 7 FPG readings done within a 10 day period are within the target range of 5-7.2 mmol/L; Mean glucose for three consecutive prior FPG values is between 5-7.2 mmol/L; There is no severe hypoglycemia during the 7-10 day period (Severe hypoglycemia is defined as third party intervention in management of the hypoglycemia).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events		12 weeks
Number of days to first reach fasting plasma glucose target	The number of days in the study until the first day the target is reached.	12 weeks
Number of days in target range after reaching fasting plasma glucose target	The number of days after reaching target where the FPG was between 5.0 and 7.2 mmol/L (inclusive)	12 weeks
Fasting plasma glucose	Fasting plasma glucose values over the entire study period will be summarized by mean and standard deviation	12 weeks
Hemoglobin A1c (HbA1c)	The change in HbA1c will be evaluated as an expression of overall glycemic control in the two treatment arms and compared.	12 weeks
Rate of documented hypoglycemia in subjects that reach target		12 weeks
Rate of documented hypoglycemia in subjects that do not reach target		12 weeks
Proportion of all patients with hypoglycemia	A summary of any hypoglycemia, severe hypoglycemia, nocturnal hypoglycemia, day-time hypoglycemia, symptomatic hypoglycemia, probable symptomatic hypoglycemia, and asymptomatic hypoglycemia will be summarized	12 weeks
Frequency of contact with physician/HCP	The number of times subjects contacted their physician/HCP during the study	12 weeks
Diabetes Treatment Satisfaction Questionnaire (DTSQ)	A questionnaire to assess subject's overall satisfaction with their diabetes treatment	12 weeks
Hypoglycemia Fear Survey (HFS)	A questionnaire to assess the subject's behaviours to avoid hypoglycemia and to measure the subjects' worries about hypoglycemia and its consequences	12 weeks
WHO-5 Well-Being Index	A questionnaire to measure emotional well-being to screening for likely depression in subjects with diabetes	12 weeks
Diabetes Distress Scale	A questionnaire to assess diabetes-related emotional distress	12 weeks
LTHome Patient Satisfaction Survey	LTHome arm only; a questionnaire to measure satisfaction of the use of the LTHome	12 weeks
Number of days subjects self-monitored their fasting plasma glucose		12 weeks
Number of dose recommendations prior to reaching target - LTHome only		12 weeks
Number of dose recommendations after target is reached - LTHome only		12 weeks
Number of days insulin glargine was taken - LTHome only		12 weeks
Reasons for disregarding LTHome advice - LTHome only	A summary of the reasons that subjects gave for not taking the insulin glargine dose recommendation given by the LTHome web tool when the recommendation was not followed	12 weeks
Serious adverse events		12 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Body weight (kg)	12 weeks
List of concomitant medications initiated after randomization	12 weeks

Collaborators and Investigators

• Sponsor: LMC Diabetes & Endocrinology Ltd.
• Collaborators: Sanofi
• Investigators: Principal Investigator: Ronnie Aronson, MD, LMC Diabetes & Endocrinology Ltd.

Publications and helpful links

General Publications

• Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. doi: 10.2337/diacare.28.5.1245. No abstract available.
• Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22.
• Hajos TR, Pouwer F, Skovlund SE, Den Oudsten BL, Geelhoed-Duijvestijn PH, Tack CJ, Snoek FJ. Psychometric and screening properties of the WHO-5 well-being index in adult outpatients with Type 1 or Type 2 diabetes mellitus. Diabet Med. 2013 Feb;30(2):e63-9. doi: 10.1111/dme.12040.
• Polonsky WH, Fisher L, Earles J, Dudl RJ, Lees J, Mullan J, Jackson RA. Assessing psychosocial distress in diabetes: development of the diabetes distress scale. Diabetes Care. 2005 Mar;28(3):626-31. doi: 10.2337/diacare.28.3.626.
• Bradley C, Plowright R, Stewart J, Valentine J, Witthaus E. The Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) evaluated in insulin glargine trials shows greater responsiveness to improvements than the original DTSQ. Health Qual Life Outcomes. 2007 Oct 10;5:57. doi: 10.1186/1477-7525-5-57.
• Canadian Diabetes Association Clinical Practice Guidelines Expert Committee; Cheng AY. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Introduction. Can J Diabetes. 2013 Apr;37 Suppl 1:S1-3. doi: 10.1016/j.jcjd.2013.01.009. Epub 2013 Mar 26. No abstract available.
• Cox DJ, Irvine A, Gonder-Frederick L, Nowacek G, Butterfield J. Fear of hypoglycemia: quantification, validation, and utilization. Diabetes Care. 1987 Sep-Oct;10(5):617-21. doi: 10.2337/diacare.10.5.617.
• Cryer PE. Hypoglycaemia: the limiting factor in the glycaemic management of Type I and Type II diabetes. Diabetologia. 2002 Jul;45(7):937-48. doi: 10.1007/s00125-002-0822-9. Epub 2002 Apr 26.
• Strange P. Treat-to-target insulin titration algorithms when initiating long or intermediate acting insulin in type 2 diabetes. J Diabetes Sci Technol. 2007 Jul;1(4):540-8. doi: 10.1177/193229680700100412.
• Morrison F, Shubina M, Turchin A. Encounter frequency and serum glucose level, blood pressure, and cholesterol level control in patients with diabetes mellitus. Arch Intern Med. 2011 Sep 26;171(17):1542-50. doi: 10.1001/archinternmed.2011.400.
• Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care. 2005 Dec;28(12):2948-61. doi: 10.2337/diacare.28.12.2948. No abstract available.
• Briscoe VJ, Davis SN. Hypoglycemia in type 1 and type 2 diabetes: physiology, pathophysiology, and management. Clinical Diabetes 24(3): 115-121, 2006.
• Seaquist ER, Miller ME, Bonds DE, Feinglos M, Goff DC Jr, Peterson K, Senior P; ACCORD Investigators. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care. 2012 Feb;35(2):409-14. doi: 10.2337/dc11-0996. Epub 2011 Dec 16.
• Swinnen SG, Hoekstra JB, DeVries JH. Insulin therapy for type 2 diabetes. Diabetes Care. 2009 Nov;32 Suppl 2(Suppl 2):S253-9. doi: 10.2337/dc09-S318. No abstract available.
• Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassai B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011 Jul 26;343:d4169. doi: 10.1136/bmj.d4169.
• Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. Am J Med. 1991 Apr;90(4):450-9.
• Petznick A. Insulin management of type 2 diabetes mellitus. Am Fam Physician. 2011 Jul 15;84(2):183-90.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimate): September 4, 2015

Study Record Updates

• Last Update Posted (Estimate): September 4, 2015
• Last Update Submitted That Met QC Criteria: September 1, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Type 2 diabetes; T2DM
• 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, Long-Acting; Insulin Glargine
• Other Study ID Numbers: INNOVATE (Other Identifier: Inovio INO-4800 Vaccine Trial for Efficacy)