Glargine Versus NPH in Patients With Chronic Kidney Disease
Condition: Type 2 Diabetes Mellitus; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic kidney disease (CKD) is one of the most common microvascular complications of
      diabetes mellitus, and it is the leading cause of end stage renal disease on developed
      countries. The CKD diagnosis and its progression require re-evaluation of hypoglycemic
      therapy and constant dosing adjustments, in order to optimize glycemic control and minimize
      its side effects. Long acting insulin analogs and its pharmacokinetics have not been studied
      through different stages of kidney disease and there is no consensus defining the appropriate
      dosing adjustment based on the glomerular filtration rate (GFR). This research project will
      compare the glycemic response to intensive insulin treatment with NPH insulin and basal
      insulin analog (insulin glargine) in type 2 diabetes (DM 2) patients with CKD stages 3 and 4.
      Patients and methods - Inclusion Criteria: DM 2 patients with CKD secondary to diabetic
      nephropathy and GFR of 15-59 ml/min/1.73m². Exclusion Criteria: Patients with systemic
      neoplasia, HIV, CKD or nephropathy from other etiologies, severe psychiatric disorders and
      pregnant women. Study design: This study consists of a randomized, cross-over, open-label
      controlled clinical trial. Patients will be randomly divided into two groups: GROUP 1 -
      insulin analog glargine once a day and GROUP 2 - NPH human insulin, three applications per
      day, both group will be treated with insulin lispro at mealtime. The laboratory tests will be
      performed at baseline and 12, 24, 36 and 48 weeks after the study start. During routine
      medical appointments will be analyzed self- monitoring of capillary blood glucose (SMBG) and
      the hypoglycemia score. After 24 weeks the basal insulin will be changed, i.e. patients using
      NPH insulin will receive insulin glargine and patients on insulin glargine will be changed to
      NPH insulin. A CGMS will be carried out at 24 and 48 weeks. Methodology: The metabolic
      profile will be evaluated throughout SMBG; biochemical, hormonal and hematological
      measurements; hypoglycemia score and CGMS. Statistical analysis will be performed using
      comparative descriptive analyzes, such as chi-square distribution, t-test and non-parametric
      tests. Analyze of data CGMS will include the area under the curve and the related statistic.
      Finally, logistic regression models will be adopted to evaluate the effect of the treatment
      on the several variables in question.
    

Detailed description: 
      This study consists of a randomized, cross-over, open-label controlled clinical trial.
      Randomized patients will be allocated alternately into two groups to receive the following
      therapies: GROUP 1 - insulin analog glargine once a day associated to insulin lispro at
      mealtime and GROUP 2 - NPH human insulin, three applications per day ( breakfast, lunch and
      bedtime) and insulin lispro at mealtime. Patients receiving insulin NPH plus insulin lispro
      will be oriented to mix both of them in the same syringe at breakfast and lunchtime. The
      laboratory tests will be performed at baseline and 12, 24, 36 and 48 weeks after the study
      start. During routine medical appointments the patient should bring the self- monitoring of
      capillary blood glucose (SMBG), eight points per day once a week, and hypoglycemia score.

      After 24 weeks of insulin therapy, a continuous glucose monitoring system (CGMS) will be
      implemented for three days, and after that, the basal insulin changed i.e. patients using NPH
      insulin will receive insulin glargine and patients on insulin glargine will be changed to NPH
      insulin, both groups will keep insulin lispro before meals. A new CGMS will be carried out 24
      weeks after therapy has been changed. Methodology: The metabolic profile will be evaluated
      throughout SMBG; biochemical, hormonal and hematological measurements; hypoglycemia score and
      CGMS (Medtronic/Northridge, CA). All randomized patients who use at least one dose of any
      study treatment will be considered in the Intent-to-treat (ITT) population. The initial plan
      is to randomize 40 patients, assuming a drop-out rate of 15%, to obtain a sample size of at
      least 34 randomized patients. .Statistical analysis will be performed using comparative
      descriptive analyzes, such as chi-square distribution, t-test and non-parametric tests.
      Analyze of data CGMS will include the area under the curve and the related statistic.
      Finally, logistic regression models will be adopted to evaluate the effect of the treatment
      on the several variables in question.
    

Intervention name(s): Glargine insulin; NPH insulin
Intervention type(s): Drug; Drug
Intervention description(s): The initial insulin dose for those randomized to IGlar was 80% of the total daily NPH dose that was being discontinued. All of them had pre-prandial Regular insulin switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. After 24 weeks, basal insulins were switched; in other words, individuals on IGlar in the first period switched to INPH, and the doses of pre-meal insulin were sustained; The same total daily NPH insulin dose was maintained for those randomized to INPH. All of them had pre-prandial Regular insulin (Humulin R™, Lilly, Brazil) switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. . After 24 weeks, basal insulins were switched; in other words, individuals on NPH in the first period switched to glargine insulin, and the doses of pre-meal insulin were sustained.
Other intervention name(s): Lantus insulin ™, Sanofi-Aventis, Brazil; Humulin N™, Lilly, Brazil
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Glargine insulin; Chronic Kidney Disease; CGMS