Beta-Cell Function and Sitagliptin Trial (BEST)

NCT ID: NCT00420511

Last Updated: 2012-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-09-30

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sitagliptin

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

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

sitagliptin 100 mg once a day

metformin

Intervention Type: DRUG

metformin 1000 mg twice a day (bid) by mouth (po)

Placebo arm

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo once a day

metformin

Intervention Type: DRUG

metformin 1000 mg twice a day (bid) by mouth (po)

Interventions

Sitagliptin

sitagliptin 100 mg once a day

Intervention Type: DRUG

Placebo

placebo once a day

Intervention Type: DRUG

metformin

metformin 1000 mg twice a day (bid) by mouth (po)

Intervention Type: DRUG

Other Intervention Names

januvia; glucophage

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bernard Zinman

Director, Leadership Sinai Centre for Diabetes

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernard Zinman, MD

Role: PRINCIPAL_INVESTIGATOR

Leadership Sinai Centre for Diabetes, University of Toronto

Ravi Retnakaran, MD

Role: PRINCIPAL_INVESTIGATOR

Leadership Sinai Centre for Diabetes, University of Toronto

Locations

Leadership Sinai Centre for Diabetes

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 25495067 (View on PubMed)

Other Identifiers

065-00

Identifier Type: -

Identifier Source: org_study_id