Beta-Cell Function and Sitagliptin Trial (BEST)
Overview[ - collapse ][ - ]
| 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 | Type 2 Diabetes Mellitus |
| Intervention | Drug: Sitagliptin Drug: Placebo Drug: metformin |
| Phase | Phase 2 |
| Sponsor | Samuel Lunenfeld Research Institute, Mount Sinai Hospital |
| Responsible Party | 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 |
Tracking Information[ + expand ][ + ]
| First Received Date | January 10, 2007 |
|---|---|
| Last Updated Date | December 28, 2011 |
| Start Date | January 2007 |
| Estimated Primary Completion Date | September 2009 |
| Current 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. |
| Current Secondary Outcome Measures |
|
Descriptive Information[ + expand ][ + ]
| Brief Title | Beta-Cell Function and Sitagliptin Trial (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 |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Type 2 Diabetes Mellitus |
| Intervention | Drug: Sitagliptin sitagliptin 100 mg once a day Other Names: januviaDrug: Placebo placebo once a day Drug: metformin metformin 1000 mg twice a day (bid) by mouth (po) Other Names: glucophage |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 21 |
| Estimated Completion Date | September 2009 |
| Estimated Primary Completion Date | September 2009 |
| Eligibility 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 |
| Gender | Both |
| Ages | 30 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Canada |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00420511 |
|---|---|
| Other Study ID Numbers | 065-00 |
| Has Data Monitoring Committee | No |
| Information Provided By | Samuel Lunenfeld Research Institute, Mount Sinai Hospital |
| Study Sponsor | Samuel Lunenfeld Research Institute, Mount Sinai Hospital |
| Collaborators | Merck Sharp & Dohme Corp. |
| Investigators | Principal Investigator: Bernard Zinman, MD Leadership Sinai Centre for Diabetes, University of TorontoPrincipal Investigator: Ravi Retnakaran, MD Leadership Sinai Centre for Diabetes, University of Toronto |
| Verification Date | December 2011 |
Locations[ + expand ][ + ]
| Leadership Sinai Centre for Diabetes | Toronto, Ontario, Canada, M5T 3L9 |
|---|