search
Back to results

Beta-Cell Function and Sitagliptin Trial (BEST) (BEST)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Sitagliptin
Placebo
metformin
Sponsored by
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 diabetes, beta-cell function, sitagliptin, intensive insulin therapy

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Leadership Sinai Centre for Diabetes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sitagliptin

Placebo arm

Arm Description

Sitagliptin 100mg once a day (od) by mouth (po)

Placebo once a day (od) by mouth (po)

Outcomes

Primary Outcome Measures

Preservation of Beta-cell Function Measured by Area-under-the-curve (C-peptide/Glucose)/HOMA-IR
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
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
Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year
Time to Loss of Glycemic Control
Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy

Full Information

First Posted
January 10, 2007
Last Updated
December 28, 2011
Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT00420511
Brief Title
Beta-Cell Function and Sitagliptin Trial (BEST)
Acronym
BEST
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Type 2 diabetes, beta-cell function, sitagliptin, intensive insulin therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sitagliptin
Arm Type
Experimental
Arm Description
Sitagliptin 100mg once a day (od) by mouth (po)
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
Placebo once a day (od) by mouth (po)
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
januvia
Intervention Description
sitagliptin 100 mg once a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo once a day
Intervention Type
Drug
Intervention Name(s)
metformin
Other Intervention Name(s)
glucophage
Intervention Description
metformin 1000 mg twice a day (bid) by mouth (po)
Primary Outcome Measure Information:
Title
Preservation of Beta-cell Function Measured by Area-under-the-curve (C-peptide/Glucose)/HOMA-IR
Description
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.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Insulinogenic Index Divided by HOMA-IR at 48 Weeks
Description
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
Time Frame
48 weeks
Title
Fasting Blood Glucose at 48 Weeks
Time Frame
48 weeks
Title
Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year
Time Frame
1 year
Title
Time to Loss of Glycemic Control
Time Frame
1 year
Title
Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women between the ages of 30 and 75 inclusive Physician-diagnosed type 2 diabetes on 0-2 oral hypoglycemic agents Negative for anti-glutamic acid decarboxylase (anti-GAD_ antibodies (to rule out Latent Autoimmune Diabetes of Adults (LADA) 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: Current insulin therapy Type 1 diabetes or secondary forms of diabetes Any major illness with a life expectancy of < 5 years or that may interfere with the patient's participation in the study Involvement in any other study requiring drug therapy 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) 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 Excessive alcohol consumption, defined as > 14 alcoholic drinks per week for males and > 9 alcoholic drinks per week for females 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 History of serious arrhythmia or atrioventricular block on baseline electrocardiogram Uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg) Unwillingness to undergo multiple daily insulin injection therapy for 4 weeks Unwillingness to perform capillary blood glucose monitoring at least 4 times per day during intensive insulin therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernard Zinman, MD
Organizational Affiliation
Leadership Sinai Centre for Diabetes, University of Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ravi Retnakaran, MD
Organizational Affiliation
Leadership Sinai Centre for Diabetes, University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leadership Sinai Centre for Diabetes
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3L9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
25495067
Citation
Stein CM, Kramer CK, Zinman B, Choi H, Opsteen C, Retnakaran R. Clinical predictors and time course of the improvement in beta-cell function with short-term intensive insulin therapy in patients with Type 2 diabetes. Diabet Med. 2015 May;32(5):645-52. doi: 10.1111/dme.12671. Epub 2015 Jan 7.
Results Reference
derived

Learn more about this trial

Beta-Cell Function and Sitagliptin Trial (BEST)

We'll reach out to this number within 24 hrs