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Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Pilot Study)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier:
NCT01755468
First received: December 19, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). The investigators propose a pilot randomized controlled trial to determine whether intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve pancreatic beta-cell function and maintain glycemic control early in the course of type 2 diabetes.


Condition Intervention Phase
Type 2 Diabetes
Drug: Intermittent insulin therapy
Drug: Continuous metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial to Evaluate Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes: REmission Studies Evaluating Type 2 DM - Intermittent Insulin Therapy (RESET-IT Pilot Study)

Resource links provided by NLM:


Further study details as provided by Mount Sinai Hospital, Canada:

Primary Outcome Measures:
  • Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index.


Secondary Outcome Measures:
  • Baseline-adjusted glycemic control at 2-years. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)


Other Outcome Measures:
  • Achievement of target glycemic control [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Achievement of target glycemic control will be assessed by the proportion of participants with A1c <7.0%

  • achievement of glucose tolerance in the non-diabetic range [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The proportion of participants with glucose tolerance in the non-diabetic range will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.

  • achievement of normal glucose tolerance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The proportion of participants with normal glucose tolerance will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.

  • insulin sensitivity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Insulin sensitivity will be measured by Matsuda index, a clamp-validated measure of whole-body insulin sensitivity that can be obtained from the oral glucose tolerance test


Estimated Enrollment: 24
Study Start Date: April 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Continuous metformin
After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy. Metformin will be initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months).
Drug: Continuous metformin
Other Name: Metformin
Experimental: Intermittent insulin therapy
After a 3-week course of intensive insulin therapy, participants will receive intermittent intensive insulin therapy for 2 weeks every 3 months. The 2-week course of insulin therapy will be repeated at 3-, 6-, 9-, 12-, 15-,18- and 21-months, with final outcome measurement performed at 24-months
Drug: Intermittent insulin therapy
Other Name: Basal insulin glargine and pre-meal insulin lispro

Detailed Description:

In this study, eligible patients with type 2 diabetes will be randomized to either intermittent insulin therapy or continuous metformin therapy, after both arms have first undergone a short course of intensive insulin therapy. The hypothesis under study is whether intermittent insulin therapy can better preserve beta-cell function.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women between the ages of 30 and 80 years inclusive
  2. T2DM diagnosed by a physician </= 5 years prior to enrolment
  3. Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies
  4. On either no anti-diabetic medication or on metformin monotherapy, with no change in dose/regimen within 4 weeks prior to enrolment
  5. A1c at screening between 5.5% and 9.0% inclusive if on metformin, or between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication
  6. BMI >/= 23 kg/m2
  7. Negative pregnancy test at recruitment for all women with childbearing potential

Exclusion Criteria:

  1. Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, GLP-1 agonist or dipeptidyl peptidase-4 inhibitor
  2. Type 1 diabetes or secondary forms of diabetes
  3. History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
  4. Any major illness with a life expectancy of <5 years
  5. Hypersensitivity to insulin, metformin or the formulations of these products
  6. Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) <50 ml/min
  7. Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, previous liver transplant) or transaminases >2.5 X upper limit of normal
  8. History of congestive heart failure
  9. Excessive alcohol consumption, defined as >14 alcoholic drinks per week for males and >9 alcoholic drinks per week for females
  10. Unwillingness to administer insulin therapy or perform capillary blood glucose monitoring at least 4 times per day while receiving IIT
  11. Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study or the first 3 months after the study. Reliable contraception includes birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide.
  12. Non-adherence to the induction phase or any factor likely to limit adherence to the study protocol, in the opinion of the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755468

Locations
Canada, Ontario
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G1X5
Sponsors and Collaborators
Mount Sinai Hospital, Canada
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Ravi Retnakaran, MD Mount Sinai Hospital, Toronto
Principal Investigator: Bernard Zinman, MD Mount Sinai Hospital, Toronto
  More Information

No publications provided

Responsible Party: Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier: NCT01755468     History of Changes
Other Study ID Numbers: 12-0263-A Pilot
Study First Received: December 19, 2012
Last Updated: July 28, 2014
Health Authority: Canada: Health Canada

Keywords provided by Mount Sinai Hospital, Canada:
beta-cell function, type 2 diabetes, intermittent insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014