Type 2 DiabetesPhase 3PREVAILNCT02194595
Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)
A Phase 3 study testing Basal insulin and exenatide, Basal insulin only and Basal insulin and bolus insulin 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?
- Basal insulin and exenatide, Basal insulin only and Basal insulin and bolus insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2014to Feb 2022
- 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 ≤7 years prior to enrolment
- On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4 weeks
- A1c at screening between 5.5% and 9.0% inclusive if on anti-diabetic medications, 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 or a glucagon-like peptide-1 (GLP-1) agonist
- Type 1 diabetes or secondary forms of diabetes
- History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
- Hypersensitivity to insulin, exenatide, or the formulations of these products
- Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR)<30 ml/min by Modification of Diet in Renal Disease (MDRD) formula
- History of pancreatitis
Show all 12Show fewer
- Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (MTC)
- Personal history of non-familial medullary thyroid carcinoma (MTC)
- Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)
- Unwillingness to perform capillary glucose monitoring at least 4 times a day during treatment
- 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.
- Any factor likely to limit adherence to the protocol, in the opinion of investigator
Trial locations and contacts
1 site in 1 country.
About this 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 randomized controlled trial to determine whether combining basal insulin with a new medication called exenatide is a therapeutic strategy that can preserve beta-cell function early in the course of type 2 diabetes.
Read the detailed description
In this open-label, parallel-arm randomized controlled trial, adults with T2DM of ≤7 years duration on 0-2 anti-diabetic medications will be randomized to 8-weeks treatment with either (i) basal insulin glargine, (ii) intensive insulin therapy consisting of glargine and pre-meal insulin lispro, or (iii) glargine and the GLP-1 agonist exenatide (twice daily). They will then go into a 12-week washout on lifestyle modification only. Beta-cell function will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks. The primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.
- Conditions
- Type 2 Diabetes
- Being tested
- Basal insulin and exenatide, Basal insulin only, Basal insulin and bolus insulin
- Keywords
- type 2 diabetes, beta-cell function, GLP-1, insulin
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Basal insulin and exenatideDrug
Also called Basal insulin glargine, Exenatide
Basal insulin onlyDrug
Also called Basal insulin glargine
Basal insulin and bolus insulinDrug
Also called Basal insulin glargine, Pre-meal insulin lispro
| Study group | Role | What they receive |
|---|---|---|
| Basal insulin and exenatide | Experimental | Participants in this arm will undergo an 8-week course of treatment with exenatide and insulin glargine. Exenatide will be initiated at 5ug subcutaneous (sc) bid (before breakfast and before dinner) for the first 4 weeks, followed by 10ug bid for the next 4 weeks. Glargine sc injection at bedtime will be titrated to fasting glucose. Receives: Drug: Basal insulin and exenatide |
| Basal insulin only | Active comparator | Participants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose. Receives: Drug: Basal insulin only |
| Basal Insulin and bolus insulin | Active comparator | Participants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal. Receives: Drug: Basal insulin and bolus insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean beta-cell function over the 8-week treatment period, measured using the 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. The primary outcome comparison is between the glargine/exenatide and glargine only arms.
Measured: 8 weeks
Secondary outcomes (4)
Baseline-adjusted beta-cell function at 20 weeks
The secondary outcome of baseline-adjusted beta-cell function at 20 weeks will be measured with the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
Measured: 20 weeks
Baseline-adjusted glycemic control at 20 weeks
The secondary outcome of baseline-adjusted glycemic control at 20 weeks will be assessed by A1c (glycated hemoglobin)
Measured: 20 weeks
Endothelial function at 8 weeks
Endothelial function will be assessed as the digital endothelial vasomotor function in response to reactive hyperemia using pulse amplitude tonometry, which will be measured by the pulse amplitude response to hyperemia (PAT ratio)
Measured: 8 weeks
Baseline-adjusted glycemic control at 8 weeks
Baseline-adjusted glycemic control at 8 weeks will be measured by A1c
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2014 (estimated)
- Study startSep 2014
- Primary completionDec 2021
- Study completionFeb 2022
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
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), University of Toronto
- Responsible party
- Sponsor
- Investigators
- Ravi Retnakaran, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02194595
- Sponsor's protocol ID
- 14-0128-A
- Acronym
- PREVAIL
- Status last verified
- Apr 2022
- First submitted
- 16 Jul 2014
- Last updated
- 11 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Retnakaran R, Pu J, Ye C, Emery A, Kramer CK, Zinman B. The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes. Cardiovasc Diabetol. 2023 Mar 9;22(1):50. doi: 10.1186/s12933-023-01781-z.
PubMed 36894921
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)
- ClinicalTrials.gov ID
- NCT02194595
- Acronym / sponsor ID
- PREVAIL / 14-0128-A
- Conditions
- Type 2 Diabetes
- Keywords
- type 2 diabetes, beta-cell function, GLP-1, insulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), University of Toronto
- Study start
- Sep 2014
- Primary completion
- Dec 2021 (actual)
- Study completion
- Feb 2022 (actual)
- First posted
- 18 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 combining basal insulin with a new medication called exenatide is a therapeutic strategy that can preserve beta-cell function early in the course of type 2 diabetes.
Detailed description
In this open-label, parallel-arm randomized controlled trial, adults with T2DM of ≤7 years duration on 0-2 anti-diabetic medications will be randomized to 8-weeks treatment with either (i) basal insulin glargine, (ii) intensive insulin therapy consisting of glargine and pre-meal insulin lispro, or (iii) glargine and the GLP-1 agonist exenatide (twice daily). They will then go into a 12-week washout on lifestyle modification only. Beta-cell function will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks. The primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Basal insulin and exenatide | Experimental | Drug: Basal insulin and exenatideParticipants in this arm will undergo an 8-week course of treatment with exenatide and insulin glargine. Exenatide will be initiated at 5ug subcutaneous (sc) bid (before breakfast and before dinner) for the first 4 weeks, followed by 10ug bid for the next 4 weeks. Glargine sc injection at bedtime will be titrated to fasting glucose. |
| Basal insulin only | Active comparator | Drug: Basal insulin onlyParticipants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose. |
| Basal Insulin and bolus insulin | Active comparator | Drug: Basal insulin and bolus insulinParticipants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women between the ages of 30 and 80 years inclusive
- T2DM diagnosed by a physician ≤7 years prior to enrolment
- On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4 weeks
- A1c at screening between 5.5% and 9.0% inclusive if on anti-diabetic medications, or between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication
- BMI ≥ 23 kg/m2
Key exclusion criteria (12 listed)
- Current anti-diabetic treatment with insulin or a glucagon-like peptide-1 (GLP-1) agonist
- Type 1 diabetes or secondary forms of diabetes
- History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
- Hypersensitivity to insulin, exenatide, or the formulations of these products
- Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR)<30 ml/min by Modification of Diet in Renal Disease (MDRD) formula
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 |
|---|---|---|
| Basal insulin and exenatideAlso: Basal insulin glargine, Exenatide | Drug | Basal insulin and exenatide |
| Basal insulin onlyAlso: Basal insulin glargine | Drug | Basal insulin only |
| Basal insulin and bolus insulinAlso: Basal insulin glargine, Pre-meal insulin lispro | Drug | Basal Insulin and bolus insulin |
Primary outcome
Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
Time frame: 8 weeks
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. The primary outcome comparison is between the glargine/exenatide and glargine only arms.
4 secondary outcomes
Baseline-adjusted beta-cell function at 20 weeks
Time frame: 20 weeks
Baseline-adjusted glycemic control at 20 weeks
Time frame: 20 weeks
Endothelial function at 8 weeks
Time frame: 8 weeks
Baseline-adjusted glycemic control at 8 weeks
Time frame: 8 weeks
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 11 Apr 2022.
- Derived from this study: PubMed 36894921Retnakaran R, Pu J, Ye C, Emery A, Kramer CK, Zinman B. The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes. Cardiovasc Diabetol. 2023 Mar 9;22(1):50. doi: 10.1186/s12933-023-01781-z.
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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 Basal insulin and exenatide, Basal insulin only and Basal insulin and bolus insulin 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 6 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 11 Apr 2022. 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?
Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) (time frame: 8 weeks). 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 NCT02194595, 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 11 Apr 2022.