Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

The LANCET Trial: A Trial of Long-acting Insulin Injection to Reduce C-reactive Protein in Patients With Type 2 Diabetes

This study has been terminated.
(Interim analyses demonstrated futility. Thus, recruitment curtailed 10/08.)
Sponsor:
Collaborator:
Sanofi
Information provided by:
Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00366301
First received: August 17, 2006
Last updated: October 26, 2010
Last verified: October 2010

August 17, 2006
October 26, 2010
August 2006
April 2009   (final data collection date for primary outcome measure)
Percentage Reduction in C-reactive Protein (CRP) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
percentage reduction in C-reactive protein (CRP)
Complete list of historical versions of study NCT00366301 on ClinicalTrials.gov Archive Site
Not Provided
  • insulin sensitivity and glycemic control
  • change in lipids, specifically total cholesterol, LDL, HDL, triglycerides
  • change in non-lipid biomarkers, specifically IL-6, TNF-alpha, RII, PAI-1 antigen, tPA antigen, adiponectin, leptin
  • change in weight
  • marked hypoglycemia
Not Provided
Not Provided
 
The LANCET Trial: A Trial of Long-acting Insulin Injection to Reduce C-reactive Protein in Patients With Type 2 Diabetes
The LANCET Trial: A Randomized Clinical Trial of Lantus for C-reactive Protein Reduction in Early Treatment of Type 2 Diabetes

The purpose of this study, which is being conducted at 100 centers throughout the United States, is to determine whether Lantus, a long-acting insulin injection, either alone or in combination with metformin, is effective in reducing C-reactive protein (CRP) in adults with type 2 diabetes. CRP is a marker of chronic low-level inflammation, a new risk factor for diabetes, heart attack, stroke, and other cardiovascular events.

Study Rationale

Low-grade systemic inflammation as indicated by elevated levels of C-reactive protein (CRP) is often present in patients with type 2 diabetes. Individuals with type 2 diabetes represent a vulnerable population in which cardiovascular event rates are high and among whom CRP reduction may have the greatest impact. While several classes of oral hypoglycemic agents have been shown to lower CRP, data are not available for newer formulations of long-acting insulins such as Lantus (insulin glargine injection) and no study has comprehensively evaluated the relative merit of insulin-providing versus insulin-sensitizing strategies for this purpose.

Investigational Plan

This is a multicenter, community-based, randomized 2x2 factorial trial of Lantus and metformin among patients with type 2 diabetes treated with either diet or oral monotherapy (other than metformin) only who have poor glycemic control and elevated CRP. The primary endpoint is change in CRP. Secondary endpoints include improvement in insulin sensitivity, glycemic control, blood lipids, as well as selected inflammatory and prothrombotic markers, and adipokine levels.

Limited data suggest that short-term insulin administration in patients with poorly controlled type 2 diabetes may lower CRP, but the benefit of CRP reduction that is unique to insulin therapy and independent of glycemic control per se remains uncertain. The insulin-sensitizing agent metformin, a mainstay of anti-diabetic therapy, has been shown to reduce macrovascular complications among patients with type 2 diabetes and, in some but not all randomized clinical trials, also has a modest CRP-lowering effect. This study is designed to assess whether the use of Lantus either alone or in combination with metformin lowers CRP over a 14-week treatment period.

Eligible men and women age 18 to 79 years with early diabetes on diet only or oral monotherapy with baseline HbA1c 7.0-10% and CRP greater than or equal to 2.0 mg/l will be randomized in a 2X2 factorial fashion as follows. First, participants will be assigned at random to open-label Lantus or no insulin. Then, within these two categories, subjects will be assigned at random to metformin or placebo. Thus, the four resultant treatment groups are Lantus injection and placebo pill, Lantus injection and metformin pill, metformin pill alone, and placebo pill alone. All patients will receive diet and exercise counseling.

This study design will permit testing of the overall effect of Lantus as well as the effect of combination therapy with metformin for CRP reduction at a targeted level of glycemic control (fingerstick fasting blood glucose < 110 mg/dl). All participants will be provided with a glucometer for fingerstick glucose testing calibrated to report plasma-referenced values.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes
  • Drug: Insulin glargine injection
    Once daily for 14 weeks
    Other Name: Lantus
  • Drug: metformin
    Up to 4 pils per day (2g per day) maximum
  • Drug: Placebo pill
    Up to 4 pills per day
  • Placebo Comparator: Placebo pill
    Placebo pill
    Intervention: Drug: Placebo pill
  • Active Comparator: Metformin Pill
    Metformin pill
    Intervention: Drug: metformin
  • Active Comparator: Insulin Glargine plus placebo pill
    Insulin glargine plus placebo pill
    Interventions:
    • Drug: Insulin glargine injection
    • Drug: Placebo pill
  • Active Comparator: Insulin Glargine plus metformin pill
    Insulin Glargine plus metformin pill
    Interventions:
    • Drug: Insulin glargine injection
    • Drug: metformin
Pradhan AD, Everett BM, Cook NR, Rifai N, Ridker PM. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA. 2009 Sep 16;302(11):1186-94.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
500
April 2009
April 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Men and women aged 18 to 79
  • Type 2 diabetes, treated only by diet or oral drugs other than metformin
  • HbA1c greater than or equal to 7% and less than or equal to 10%
  • C-reactive protein greater than or equal to 2 mg/L

Exclusion Criteria:

  • Baseline use of metformin or insulin
  • Type 1 diabetes, history of ketoacidosis or positive anti-GAD antibody
  • History of congestive heart failure requiring drug therapy
  • Active liver disease
  • Kidney impairment
  • Recent initiation or change in dose of statins, fibric acid derivatives, angiotensin receptor blockers, nonsteroidal anti-inflammatory agents, or corticosteroids
Both
18 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00366301
2006-P-000823, Lantus_L_00833
Yes
Aruna Das Pradhan, MD, MPH, Brigham & Women's Hospital, Boston, Massachusetts 02115
Brigham and Women's Hospital
Sanofi
Study Chair: Paul M Ridker, MD, MPH Brigham and Women's Hospital
Principal Investigator: Aruna Das Pradhan, MD, MPH Brigham and Women's Hospital
Brigham and Women's Hospital
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP