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

NCT02194595 | Completed Phase 3

• 1 other identifier: 14-0128-A
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Type 2 Diabetes

Keywords

type 2 diabetes; beta-cell function; GLP-1; insulin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Baseline-adjusted beta-cell function at 20 weeks

  20 weeks

• Baseline-adjusted glycemic control at 20 weeks

  20 weeks

• Endothelial function at 8 weeks

  8 weeks

• Baseline-adjusted glycemic control at 8 weeks

  8 weeks

Other Outcomes (2)

• Baseline-adjusted insulin sensitivity at 8 weeks

  8 weeks

• Baseline-adjusted insulin sensitivity at 20 weeks

  20 weeks

Study Arms (3)

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.

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.

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.

Drug: Basal insulin and bolus insulin

Interventions

Basal insulin and exenatide DRUG

Also known as: Basal insulin glargine, Exenatide

Basal insulin and exenatide

Basal insulin only DRUG

Also known as: Basal insulin glargine

Basal insulin only

Basal insulin and bolus insulin DRUG

Also known as: Basal insulin glargine, Pre-meal insulin lispro

Basal Insulin and bolus insulin

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• University of Toronto: collaborator

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

Related Publications (1)

• 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.

  PMID: 36894921 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Ravi Retnakaran, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 18, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2021
• Study Completion: February 1, 2022
• Last Updated: April 11, 2022

Record last verified: 2022-04

Locations

CA (1)