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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mount Sinai Hospital, Canada
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
University of Toronto
Information provided by (Responsible Party):
Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier:
NCT02194595
First received: July 16, 2014
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: Basal insulin and exenatide
Drug: Basal insulin only
Drug: Basal insulin and bolus insulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)

Resource links provided by NLM:


Further study details as provided by Mount Sinai Hospital, Canada:

Primary Outcome Measures:
  • Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Baseline-adjusted beta-cell function at 20 weeks [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    The secondary outcome of baseline-adjusted beta-cell function at 20 weeks will be measured with the Insulin Secretion-Sensitivity Index-2 (ISSI-2)

  • Baseline-adjusted glycemic control at 20 weeks [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    The secondary outcome of baseline-adjusted glycemic control at 20 weeks will be assessed by A1c (glycated hemoglobin)

  • Endothelial function at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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)

  • Baseline-adjusted glycemic control at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Baseline-adjusted glycemic control at 8 weeks will be measured by A1c


Other Outcome Measures:
  • Baseline-adjusted insulin sensitivity at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Baseline-adjusted insulin sensitivity at 8 weeks will be measured by Matsuda index

  • Baseline-adjusted insulin sensitivity at 20 weeks [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Baseline-adjusted insulin sensitivity at 20 weeks will be measured by Matsuda index


Estimated Enrollment: 120
Study Start Date: September 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Basal insulin and exenatide
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
Other Names:
  • Basal insulin glargine
  • Exenatide
Active Comparator: Basal insulin only
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
Other Name: Basal insulin glargine
Active Comparator: Basal Insulin and bolus insulin
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
Other Names:
  • Basal insulin glargine
  • Pre-meal insulin lispro

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies
  4. On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4 weeks
  5. 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
  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02194595

Contacts
Contact: Ravi Retnakaran, MD 416-586-4800 ext 3941 rretnakaran@mtsinai.on.ca
Contact: Bernard Zinman, MD 416-586-8747 zinman@lunenfeld.ca

Locations
Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G1X5
Contact: Ravi Retnakaran, MD    416-586-4800 ext 3941      
Principal Investigator: Ravi Retnakaran, MD         
Sponsors and Collaborators
Mount Sinai Hospital, Canada
Canadian Institutes of Health Research (CIHR)
University of Toronto
Investigators
Principal Investigator: Ravi Retnakaran, MD Mount Sinai Hospital, New York
  More Information

No publications provided

Responsible Party: Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier: NCT02194595     History of Changes
Other Study ID Numbers: 14-0128-A
Study First Received: July 16, 2014
Last Updated: September 10, 2014
Health Authority: Canada: Health Canada

Keywords provided by Mount Sinai Hospital, Canada:
type 2 diabetes
beta-cell function
GLP-1
insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Exenatide
Glargine
Insulin
Insulin Lispro
Insulin, Globin Zinc
Insulin, Long-Acting
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014