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

NCT ID: NCT01755468

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-10-31

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Continuous metformin

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Intermittent insulin therapy

Intervention Type: DRUG

Interventions

Intermittent insulin therapy

Intervention Type: DRUG

Continuous metformin

Intervention Type: DRUG

Other Intervention Names

Basal insulin glargine and pre-meal insulin lispro; Metformin

Eligibility 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi Retnakaran, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Canada

Bernard Zinman, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Canada

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Retnakaran R, Choi H, Ye C, Kramer CK, Zinman B. Two-year trial of intermittent insulin therapy vs metformin for the preservation of beta-cell function after initial short-term intensive insulin induction in early type 2 diabetes. Diabetes Obes Metab. 2018 Jun;20(6):1399-1407. doi: 10.1111/dom.13236. Epub 2018 Feb 23.

Reference Type: BACKGROUND

PMID: 29377408 (View on PubMed)

Other Identifiers

12-0263-A Pilot

Identifier Type: -

Identifier Source: org_study_id