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
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: 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
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014