Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)

Type 2 Diabetes Clinical Trial

— PREVAIL  

Official title:

Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02194595
• Other study ID #: 14-0128-A
• Status: Completed
• Phase: Phase 3
• Start date: September 2014
• Est. completion date: February 2022

Study information

• Verified date: April 2022
• Source: Mount Sinai Hospital, Canada
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: February 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Men and women between the ages of 30 and 80 years inclusive

2. T2DM diagnosed by a physician =7 years prior to enrolment

3. On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4 weeks

4. 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

5. BMI = 23 kg/m2

6. Negative pregnancy test at recruitment for all women with childbearing potential

Exclusion Criteria:

1. Current anti-diabetic treatment with insulin or a glucagon-like peptide-1 (GLP-1) agonist

2. Type 1 diabetes or secondary forms of diabetes

3. History of hypoglycemia unawareness or severe hypoglycemia requiring assistance

4. Hypersensitivity to insulin, exenatide, or the formulations of these products

5. Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR)<30 ml/min by Modification of Diet in Renal Disease (MDRD) formula

6. History of pancreatitis

7. Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (MTC)

8. Personal history of non-familial medullary thyroid carcinoma (MTC)

9. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)

10. Unwillingness to perform capillary glucose monitoring at least 4 times a day during treatment

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. Any factor likely to limit adherence to the protocol, in the opinion of investigator

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Basal insulin and exenatide

• Basal insulin only

• Basal insulin and bolus insulin

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada	Canadian Institutes of Health Research (CIHR), University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Baseline-adjusted insulin sensitivity at 8 weeks	Baseline-adjusted insulin sensitivity at 8 weeks will be measured by Matsuda index	8 weeks
Other	Baseline-adjusted insulin sensitivity at 20 weeks	Baseline-adjusted insulin sensitivity at 20 weeks will be measured by Matsuda index	20 weeks
Primary	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.	8 weeks
Secondary	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)	20 weeks
Secondary	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)	20 weeks
Secondary	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)	8 weeks
Secondary	Baseline-adjusted glycemic control at 8 weeks	Baseline-adjusted glycemic control at 8 weeks will be measured by A1c	8 weeks