Beta-Cell Function and Sitagliptin Trial (BEST)

NCT00420511 | Completed Phase 2 Results

• 1 other identifier: 065-00
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes; beta-cell function; sitagliptin; intensive insulin therapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Insulinogenic Index Divided by HOMA-IR at 48 Weeks

  48 weeks

• Fasting Blood Glucose at 48 Weeks

  48 weeks

• Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year

  1 year

• Time to Loss of Glycemic Control

  1 year

• Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy

  1 year

Study Arms (2)

Sitagliptin

EXPERIMENTAL

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

Drug: Sitagliptin; Drug: metformin

Placebo arm

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: metformin

Interventions

Sitagliptin DRUG

sitagliptin 100 mg once a day

Also known as: januvia

Sitagliptin

Placebo DRUG

placebo once a day

Placebo arm

metformin DRUG

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

Also known as: glucophage

Placebo arm; Sitagliptin

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Leadership Sinai Centre for Diabetes

Toronto, Ontario, M5T 3L9, Canada

Location

Related Publications (1)

• 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.

  PMID: 25495067 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

The modest sample size of this pilot study may have lacked sufficient statistical power to detect an effect on preservation of beta-cell function.

Results Point of Contact

• Title: Dr. Ravi Retnakaran
• Organization: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital

rretnakaran@mtsinai.on.ca

416-586-4800

Study Officials

• Bernard Zinman, MD

  Leadership Sinai Centre for Diabetes, University of Toronto

  PRINCIPAL INVESTIGATOR

• Ravi Retnakaran, MD

  Leadership Sinai Centre for Diabetes, University of Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Leadership Sinai Centre for Diabetes

Study Record Dates

• First Submitted: January 10, 2007
• First Posted: January 11, 2007
• Study Start: January 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: January 2, 2012
• Results First Posted: December 29, 2011

Record last verified: 2011-12

Locations

CA (1)