Beta-Cell Function and Sitagliptin Trial (BEST)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bernard Zinman, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
ClinicalTrials.gov Identifier:
NCT00420511
First received: January 10, 2007
Last updated: December 28, 2011
Last verified: December 2011
  Purpose

Type 2 diabetes mellitus (T2DM) 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 double-blind, randomized controlled pilot study comparing the effect of sitagliptin (a novel anti-diabetic drug with beta-cell protective potential) versus placebo, on the preservation of beta-cell function over one year in patients with T2DM on metformin, the first-line agent for the treatment of T2DM (ie. the study groups will be (i) sitagliptin and metformin versus (ii) placebo and metformin). This study may demonstrate an important beta-cell protective capacity of sitagliptin.

Hypothesis: In patients with T2DM on metformin, treatment with the DPP-IV inhibitor sitagliptin will preserve pancreatic beta-cell function.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Placebo
Drug: metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Pilot Study Assessing the Effect of Sitagliptin on the Preservation of Beta-Cell Function in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Samuel Lunenfeld Research Institute, Mount Sinai Hospital:

Primary Outcome Measures:
  • Preservation of Beta-cell Function Measured by Area-under-the-curve (C-peptide/Glucose)/HOMA-IR [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Area-under-the-C-peptide-curve (AUCCpep) and area-under-the-glucose-curve (AUCgluc) from 0 to 240 minutes during meal tests were calculated using the trapezoidal rule. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Beta-cell function was assessed using the ratio of total AUCCpep to AUCgluc divided by HOMA-IR (AUCCpep/gluc/HOMA-IR), a measure of insulin secretion in the context of ambient insulin sensitivity, analogous to the disposition index and adaptation index. Higher AUCCpep/gluc/HOMA-IR is indicative of better beta-cell function.


Secondary Outcome Measures:
  • Insulinogenic Index Divided by HOMA-IR at 48 Weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Insulinogenic index was calculated as the incremental change in insulin from 0 to 30 minutes divided by the incremental change in glucose over the same period of time. Insulinogenic index divided by HOMA-IR provides an additional measure of beta-cell function. A higher value indicates better beta-cell function

  • Fasting Blood Glucose at 48 Weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to Loss of Glycemic Control [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: January 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin 100mg once a day (od) by mouth (po)
Drug: Sitagliptin
sitagliptin 100 mg once a day
Other Name: januvia
Drug: metformin
metformin 1000 mg twice a day (bid) by mouth (po)
Other Name: glucophage
Placebo Comparator: Placebo arm
Placebo once a day (od) by mouth (po)
Drug: Placebo
placebo once a day
Drug: metformin
metformin 1000 mg twice a day (bid) by mouth (po)
Other Name: glucophage

Detailed Description:

Medications currently used in the treatment of T2DM have not been shown to modify the progressive decline in beta-cell function that occurs over time. Recent evidence, however, suggests that a new class of anti-diabetic medications, called dipeptidyl peptidase-IV (DPP-IV) inhibitors, may be able to protect beta cells and hence alter the natural history of T2DM. We thus wish to study the effect of sitagliptin (a DPP-IV inhibitor) on the preservation of beta-cell function in patients with T2DM randomized to either (i) sitagliptin and metformin or (ii) placebo and metformin.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women between the ages of 30 and 75 inclusive
  2. Physician-diagnosed type 2 diabetes on 0-2 oral hypoglycemic agents
  3. Negative for anti-glutamic acid decarboxylase (anti-GAD_ antibodies (to rule out Latent Autoimmune Diabetes of Adults (LADA)
  4. A1c at screening between 6.5% and 9% inclusive if on no oral hypoglycemic agents or 6.0% and 9.0% inclusive if on 1-2 oral hypoglycemic agents

Exclusion Criteria:

  1. Current insulin therapy
  2. Type 1 diabetes or secondary forms of diabetes
  3. Any major illness with a life expectancy of < 5 years or that may interfere with the patient's participation in the study
  4. Involvement in any other study requiring drug therapy
  5. Renal dysfunction as evidenced by serum creatinine >/= 136 umol/L for males or >/= 124 umol/L for females or abnormal creatinine clearance (< 60 ml/min by Modification of Diet in Renal Disease (MDRD) formula)
  6. Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases > 2.5 times the upper limit of normal
  7. Excessive alcohol consumption, defined as > 14 alcoholic drinks per week for males and > 9 alcoholic drinks per week for females
  8. Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study. Reliable contraception includes: birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide. Any women who miss a menstrual period or think that they may be pregnant must have a pregnancy test as soon as possible
  9. History of serious arrhythmia or atrioventricular block on baseline electrocardiogram
  10. Uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)
  11. Unwillingness to undergo multiple daily insulin injection therapy for 4 weeks
  12. Unwillingness to perform capillary blood glucose monitoring at least 4 times per day during intensive insulin therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00420511

Locations
Canada, Ontario
Leadership Sinai Centre for Diabetes
Toronto, Ontario, Canada, M5T 3L9
Sponsors and Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Bernard Zinman, MD Leadership Sinai Centre for Diabetes, University of Toronto
Principal Investigator: Ravi Retnakaran, MD Leadership Sinai Centre for Diabetes, University of Toronto
  More Information

No publications provided

Responsible Party: Bernard Zinman, Director, Leadership Sinai Centre for Diabetes, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
ClinicalTrials.gov Identifier: NCT00420511     History of Changes
Other Study ID Numbers: 065-00
Study First Received: January 10, 2007
Results First Received: June 24, 2011
Last Updated: December 28, 2011
Health Authority: Canada: Health Canada

Keywords provided by Samuel Lunenfeld Research Institute, Mount Sinai Hospital:
Type 2 diabetes
beta-cell function
sitagliptin
intensive insulin therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014