Beta-Cell Function and Sitagliptin Trial (BEST)

Type 2 Diabetes Mellitus Clinical 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00420511
• Other study ID #: 065-00
• Status: Completed
• Phase: Phase 2
• First received: January 10, 2007
• Last updated: December 28, 2011
• Start date: January 2007
• Est. completion date: September 2009

Study information

• Verified date: December 2011
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sitagliptin
sitagliptin 100 mg once a day
• Placebo
placebo once a day
• metformin
metformin 1000 mg twice a day (bid) by mouth (po)

Locations

Country	Name	City	State
Canada	Leadership Sinai Centre for Diabetes	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Samuel Lunenfeld Research Institute, Mount Sinai Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 weeks	No
Secondary	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	48 weeks	No
Secondary	Fasting Blood Glucose at 48 Weeks		48 weeks	No
Secondary	Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year		1 year	No
Secondary	Time to Loss of Glycemic Control		1 year	No
Secondary	Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy		1 year	No