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
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: Insulin glargine injection
Drug: metformin
Drug: Placebo pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The LANCET Trial: A Randomized Clinical Trial of Lantus for C-reactive Protein Reduction in Early Treatment of Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Percentage Reduction in C-reactive Protein (CRP) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Enrollment: 500
Study Start Date: August 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo pill
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: Insulin glargine injection
Once daily for 14 weeks
Other Name: Lantus
Drug: Placebo pill
Up to 4 pills per day
Active Comparator: Insulin Glargine plus metformin pill
Insulin Glargine plus metformin pill
Drug: Insulin glargine injection
Once daily for 14 weeks
Other Name: Lantus
Drug: metformin
Up to 4 pils per day (2g per day) maximum

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.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00366301

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Brigham and Women's Hospital
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
  More Information

No publications provided by Brigham and Women's Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Aruna Das Pradhan, MD, MPH, Brigham & Women's Hospital, Boston, Massachusetts 02115
ClinicalTrials.gov Identifier: NCT00366301     History of Changes
Other Study ID Numbers: 2006-P-000823, Lantus_L_00833
Study First Received: August 17, 2006
Results First Received: October 26, 2010
Last Updated: October 26, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
type 2 diabetes
insulin
insulin injection
metformin
C-reactive protein
insulin sensitivity
glycemic control
inflammation

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Contraceptive Agents, Female
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Glargine
Insulin
Metformin
Insulin, Long-Acting
Contraceptives, Oral
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014