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

October 26, 2010 updated by: Brigham and Women's Hospital

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 77 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo pill
Drug: Placebo pill
Up to 4 pills per day
Active Comparator: Metformin Pill
Metformin pill
Drug: metformin
Up to 4 pils per day (2g per day) maximum
Active Comparator: Insulin Glargine plus placebo pill
Insulin glargine plus placebo pill
Drug: Placebo pill
Up to 4 pills per day
Drug: Insulin glargine injection
Once daily for 14 weeks
Other Names:
  • Lantus
Active Comparator: Insulin Glargine plus metformin pill
Drug: metformin
Up to 4 pils per day (2g per day) maximum
Drug: Insulin glargine injection
Once daily for 14 weeks
Other Names:
  • Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage Reduction in C-reactive Protein (CRP)
Time Frame: 14 weeks
14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Sanofi

Investigators

  • Study Chair: Paul M Ridker, MD, MPH, Brigham and Women's Hospital
  • Principal Investigator: Aruna Das Pradhan, MD, MPH, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

August 17, 2006

First Submitted That Met QC Criteria

August 18, 2006

First Posted (Estimate)

August 21, 2006

Study Record Updates

Last Update Posted (Estimate)

November 25, 2010

Last Update Submitted That Met QC Criteria

October 26, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-P-000823
  • Lantus_L_00833

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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