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

Phase 3

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Continuous metformin; Drug: Intermittent insulin therapy

• Registration Number: NCT01755468
• Lead Sponsor: Mount Sinai Hospital, Canada

Brief 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 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.

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.

Study Timeline

• Study First Submitted: 2012-12-19
• Study First Submitted QC: 2012-12-21
• Study First Posted: 2012-12-24
• Study Start: 2013-04
• Primary Completion: 2017-10
• Study Completion: 2017-10
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-14
• Last Update Posted: 2018-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Continuous metformin	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).
Intermittent insulin therapy	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

Primary Outcome Measures

Name	Time	Method
Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).	2 years	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

Name	Time	Method
Baseline-adjusted glycemic control at 2-years.	2 years	The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)

Trial Locations

Locations (1)

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada