- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01755468
Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Pilot Study)
August 14, 2018 updated by: Mount Sinai Hospital, Canada
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)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Ontario
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Toronto, Ontario, Canada, M5G1X5
- Mount Sinai Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Men and women between the ages of 30 and 80 years inclusive
- T2DM diagnosed by a physician </= 5 years prior to enrolment
- Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies
- On either no anti-diabetic medication or on metformin monotherapy, with no change in dose/regimen within 4 weeks prior to enrolment
- 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
- BMI >/= 23 kg/m2
- Negative pregnancy test at recruitment for all women with childbearing potential
Exclusion Criteria:
- Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, GLP-1 agonist or dipeptidyl peptidase-4 inhibitor
- Type 1 diabetes or secondary forms of diabetes
- History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
- Any major illness with a life expectancy of <5 years
- Hypersensitivity to insulin, metformin or the formulations of these products
- Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) <50 ml/min
- Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, previous liver transplant) or transaminases >2.5 X upper limit of normal
- History of congestive heart failure
- Excessive alcohol consumption, defined as >14 alcoholic drinks per week for males and >9 alcoholic drinks per week for females
- Unwillingness to administer insulin therapy or perform capillary blood glucose monitoring at least 4 times per day while receiving IIT
- 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.
- Non-adherence to the induction phase or any factor likely to limit adherence to the study protocol, in the opinion of the investigator
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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).
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Other Names:
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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
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).
Time Frame: 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.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baseline-adjusted glycemic control at 2-years.
Time Frame: 2 years
|
The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Achievement of target glycemic control
Time Frame: 2 years
|
Achievement of target glycemic control will be assessed by the proportion of participants with A1c <7.0%
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2 years
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achievement of glucose tolerance in the non-diabetic range
Time Frame: 2 years
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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
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achievement of normal glucose tolerance
Time Frame: 2 years
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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.
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2 years
|
insulin sensitivity
Time Frame: 2 years
|
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
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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Ravi Retnakaran, MD, Mount Sinai Hospital, Canada
- Principal Investigator: Bernard Zinman, MD, Mount Sinai Hospital, Canada
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2013
Primary Completion (Actual)
October 1, 2017
Study Completion (Actual)
October 1, 2017
Study Registration Dates
First Submitted
December 19, 2012
First Submitted That Met QC Criteria
December 21, 2012
First Posted (Estimate)
December 24, 2012
Study Record Updates
Last Update Posted (Actual)
August 16, 2018
Last Update Submitted That Met QC Criteria
August 14, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12-0263-A Pilot
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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