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

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ClinicalTrials.gov Identifier: NCT00366301
Recruitment Status : Terminated (Interim analyses demonstrated futility. Thus, recruitment curtailed 10/08.)
First Posted : August 21, 2006
Results First Posted : November 25, 2010
Last Update Posted : November 25, 2010
Sponsor:
Collaborator:
Sanofi
Information provided by:
Brigham and Women's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Insulin glargine injection
Drug: metformin
Drug: Placebo pill
Enrollment 500
Recruitment Details Recruitment occurred at 73 US office-based practices between October 2006 and December 2008.
Pre-assignment Details Preenrollment evaluation comprised local laboratory testing of hsCRP,HbA1c, and safety parameters (ALT or AST and creatinine). Eligible participants were enrolled in a 2-week run-in. Ability to self-monitor fingerstick blood glucose and perform insulin injection was determined and evaluation for evidence of marked hyperglycemia was undertaken.
Arm/Group Title Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Hide Arm/Group Description Placebo pill Metformin pill Insulin glargine plus placebo pill Insulin Glargine plus metformin pill
Period Title: Overall Study
Started 124 126 126 124
Either 6W or 14W CRP Obtained 120 124 124 119
Completed 116 120 122 116
Not Completed 8 6 4 8
Reason Not Completed
Lost to Follow-up             4             4             3             7
Withdrawal by Subject             4             2             1             1
Arm/Group Title Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill Total
Hide Arm/Group Description Placebo pill Metformin pill Insulin glargine plus placebo pill Insulin Glargine plus metformin pill Total of all reporting groups
Overall Number of Baseline Participants 124 126 126 124 500
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Mean (SD) Number Analyzed 124 participants 126 participants 126 participants 124 participants 500 participants
54.0  (10.9) 53.8  (11.5) 53.8  (11.4) 54.0  (11.7) 53.9  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 126 participants 126 participants 124 participants 500 participants
Female
64
  51.6%
68
  54.0%
83
  65.9%
66
  53.2%
281
  56.2%
Male
60
  48.4%
58
  46.0%
43
  34.1%
58
  46.8%
219
  43.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 126 participants 126 participants 124 participants 500 participants
Hispanic or Latino
13
  10.5%
4
   3.2%
19
  15.1%
17
  13.7%
53
  10.6%
Not Hispanic or Latino
110
  88.7%
119
  94.4%
104
  82.5%
105
  84.7%
438
  87.6%
Unknown or Not Reported
1
   0.8%
3
   2.4%
3
   2.4%
2
   1.6%
9
   1.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 124 participants 126 participants 126 participants 124 participants 500 participants
White 91 88 95 91 365
African American 25 34 25 24 108
Other 8 4 6 9 27
1.Primary Outcome
Title Percentage Reduction in C-reactive Protein (CRP)
Hide Description [Not Specified]
Time Frame 14 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
As hsCRP was measured at both 6 and 14 weeks, linear mixed models conditioning on baseline hsCRP and adjusting for treatment stratum were constructed with the dependent variable being change in lnCRP. Any subject having either or both 6 week and 14 week measures was included.
Arm/Group Title Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Hide Arm/Group Description:
Placebo pill
Metformin pill
Insulin glargine plus placebo pill
Insulin Glargine plus metformin pill
Overall Number of Participants Analyzed 120 124 124 119
Mean (95% Confidence Interval)
Unit of Measure: Percent CRP Reduction
-19.0
(-27.8 to -9.1)
-16.1
(-25.1 to -6.1)
-2.9
(-13.2 to 8.6)
-20.1
(-28.8 to -10.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Pill, Metformin Pill, Insulin Glargine Plus Placebo Pill, Insulin Glargine Plus Metformin Pill
Comments As hsCRP was measured at both 6 and 14 weeks, linear mixed models conditioning on baseline hsCRP and adjusting for treatment stratum were constructed with the dependent variable being change in lnCRP. The means at each time point were estimated from a repeated-measures model incorporating all 3 time points. The interventions were assessed by fitting terms corresponding to study drug and treatment arm assignment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted models included terms for baseline HbA1c and weight and change in weight at each time point.
Method of Estimation Estimation Parameter Percent Change in Log CRP
Estimated Value 20
Parameter Dispersion
Type: Standard Error of the mean
Value: 10
Estimation Comments [Not Specified]
Time Frame 14 weeks
Adverse Event Reporting Description Occurrence of marked hypoglycemia, weight gain, and other adverse events were collected at each of 6 visits.
 
Arm/Group Title Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Hide Arm/Group Description Placebo pill Metformin pill Insulin glargine plus placebo pill Insulin Glargine plus metformin pill
All-Cause Mortality
Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/124 (2.42%)      8/126 (6.35%)      2/126 (1.59%)      0/124 (0.00%)    
Cardiac disorders         
Supraventricular Tachycardia Requiring Hospitalization *  0/124 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0 0/124 (0.00%)  0
Chest Pain Hospitalization *  0/124 (0.00%)  0 2/126 (1.59%)  2 1/126 (0.79%)  1 0/124 (0.00%)  0
Endocrine disorders         
Hyperglycemia Requiring Hospitalization *  1/124 (0.81%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0 0/124 (0.00%)  0
Gastrointestinal disorders         
Severe Diarrhea Requiring Hospitalization *  0/124 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0 0/124 (0.00%)  0
Gastroenteritis Hospitalization *  0/124 (0.00%)  0 2/126 (1.59%)  2 0/126 (0.00%)  0 0/124 (0.00%)  0
Infections and infestations         
Cellulitis Hospitalization *  1/124 (0.81%)  0/126 (0.00%)  0 0/126 (0.00%)  0 0/124 (0.00%)  0
Sepsis Hospitazation *  1/124 (0.81%)  1 0/126 (0.00%)  0 0/126 (0.00%)  0/124 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Traumatic Injury/Fracture *  0/124 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0 0/124 (0.00%)  0
Psychiatric disorders         
Depression *  0/124 (0.00%)  0 1/126 (0.79%)  1 0/126 (0.00%)  0 0/124 (0.00%)  0
Renal and urinary disorders         
Nephrolithiasis Requiring Hospitalization *  0/124 (0.00%)  0 0/126 (0.00%)  0 1/126 (0.79%)  1 0/124 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.5%
Placebo Pill Metformin Pill Insulin Glargine Plus Placebo Pill Insulin Glargine Plus Metformin Pill
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/124 (9.68%)      18/126 (14.29%)      21/126 (16.67%)      17/124 (13.71%)    
Endocrine disorders         
Severe Hypoglycemia  [1]  1/124 (0.81%)  1 3/126 (2.38%)  3 3/126 (2.38%)  3 6/124 (4.84%)  6
Hyperglycemia: Confirmed Fasting Glucose >= 250 mg/dl   10/124 (8.06%)  10 1/126 (0.79%)  1 4/126 (3.17%)  4 1/124 (0.81%)  1
Hyperglycemia: Any Self-Monitor Blood Glucose >= 400 mg/dl   3/124 (2.42%)  3 0/126 (0.00%)  0 3/126 (2.38%)  3 1/124 (0.81%)  1
Weight Gain >= 5% of Baseline   3/124 (2.42%)  3 4/126 (3.17%)  4 14/126 (11.11%)  14 8/124 (6.45%)  8
Gastrointestinal disorders         
Gastrointestinal Adverse Event (e.g. diarrhea not requiring hospitalization) *  3/124 (2.42%)  3 13/126 (10.32%)  13 4/126 (3.17%)  4 8/124 (6.45%)  8
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
Subjects were queried at each study visit.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Aruna Pradhan
Organization: Brigham and Women's Hospital
Phone: 617-732-8777
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
First Submitted: August 17, 2006
First Posted: August 21, 2006
Results First Submitted: October 26, 2010
Results First Posted: November 25, 2010
Last Update Posted: November 25, 2010