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

Type 2 Diabetes Clinical Trial

— RESET-IT  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02192424
• Other study ID #: 12-0263-A Main
• Status: Completed
• Phase: Phase 3
• Start date: July 2014
• Est. completion date: September 2020

Study information

• Verified date: October 2020
• Source: Mount Sinai Hospital, Canada
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 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.

Description:

In this study, eligible patients with type 2 diabetes will be randomized to either intermittent insulin therapy or not, on a background of metformin, after first undergoing a short course of intensive insulin therapy. The hypothesis under study is whether intermittent insulin therapy can preserve beta-cell function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: September 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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, glucagon-like peptide-1 (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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Metformin alone

• Metformin + Intermittent Insulin Therapy

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Achievement of target glycemic control	Achievement of target glycemic control will be assessed by the proportion of participants with A1c <7.0%	2 years
Other	achievement of glucose tolerance in the non-diabetic range	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.	2 years
Other	achievement of normal glucose tolerance	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.	2 years
Other	insulin sensitivity	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	2 years
Primary	Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).	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.	2 years
Secondary	Baseline-adjusted glycemic control at 2-years.	The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)	2 years