Clinical trial NCT02192424: Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Main Trial)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: beta-cell function,
type 2 diabetes,
intermittent insulin
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2014-07-16
Enrollment: 109
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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 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.

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, 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

Primary outcomes:
measure: Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).
timeFrame: 2 years
Secondary outcomes:
measure: Baseline-adjusted glycemic control at 2-years.
timeFrame: 2 years
Other outcomes:
measure: Achievement of target glycemic control
timeFrame: 2 years
measure: achievement of glucose tolerance in the non-diabetic range
timeFrame: 2 years
measure: achievement of normal glucose tolerance
timeFrame: 2 years
measure: insulin sensitivity
timeFrame: 2 years
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Ravi Retnakaran, MD
role: PRINCIPAL_INVESTIGATOR
References: