Type 2 DiabetesPhase 3RESET-ITNCT02192424
Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Main Trial)
A Phase 3 study testing Metformin alone and Metformin + Intermittent Insulin Therapy in people with Type 2 Diabetes, run by Mount Sinai Hospital, Canada at 1 site in Canada.
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). Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Metformin alone and Metformin + Intermittent Insulin Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2014to Sep 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, glucagon-like peptide-1 (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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Type 2 Diabetes
- Being tested
- Metformin alone, Metformin + Intermittent Insulin Therapy
- Keywords
- beta-cell function,, type 2 diabetes,, intermittent insulin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin aloneDrug
Also called metformin
Metformin + Intermittent Insulin TherapyDrug
Also called metformin,, basal insulin glargine and pre-meal insulin lispro
| Study group | Role | What they receive |
|---|---|---|
| Metformin alone | Active comparator | 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). Receives: Drug: Metformin alone |
| Metformin + Intermittent Insulin Therapy | Experimental | After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, 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). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. 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. Receives: Drug: Metformin + Intermittent Insulin Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (1)
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)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionAug 2020
- Study completionSep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Ravi Retnakaran, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02192424
- Sponsor's protocol ID
- 12-0263-A Main
- Acronym
- RESET-IT
- Status last verified
- Oct 2020
- First submitted
- 14 Jul 2014
- Last updated
- 27 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Retnakaran R, Pu J, Emery A, Harris SB, Reichert SM, Gerstein HC, McInnes N, Kramer CK, Zinman B. Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes. Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w.
PubMed 37500612
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02192424
- Acronym / sponsor ID
- RESET-IT / 12-0263-A Main
- Conditions
- Type 2 Diabetes
- Keywords
- beta-cell function,, type 2 diabetes,, intermittent insulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Jul 2014
- Primary completion
- Aug 2020 (actual)
- Study completion
- Sep 2020 (actual)
- First posted
- 16 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin alone | Active comparator | Drug: Metformin aloneAfter 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). |
| Metformin + Intermittent Insulin Therapy | Experimental | Drug: Metformin + Intermittent Insulin TherapyAfter a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, 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). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. 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. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, glucagon-like peptide-1 (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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin aloneAlso: metformin | Drug | Metformin alone |
| Metformin + Intermittent Insulin TherapyAlso: metformin,, basal insulin glargine and pre-meal insulin lispro | Drug | Metformin + Intermittent Insulin Therapy |
Primary outcome
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.
1 secondary outcome
Baseline-adjusted glycemic control at 2-years.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
- Derived from this study: PubMed 37500612Retnakaran R, Pu J, Emery A, Harris SB, Reichert SM, Gerstein HC, McInnes N, Kramer CK, Zinman B. Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes. Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi Retnakaran, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin alone and Metformin + Intermittent Insulin Therapy in people with Type 2 Diabetes, run by Mount Sinai Hospital, Canada at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02192424, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2020.