Glargine Versus NPH in Patients With Chronic Kidney Disease

Condition(s) targeted: Type 2 Diabetes Mellitus; Chronic Kidney Disease

Intervention: Glargine (Drug); NPH insulin (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University of Sao Paulo General Hospital

Official(s) and/or principal investigator(s):
Marcia S Queiroz, MD, PhD, Principal Investigator, Affiliation: Assistant Professor at Division of Endocrinology and Metabolism, Department of Internal Medicine, Clinic Hospital of the University of São Paulo Medical School

Overall contact:
Marcia Queiroz, PhD, Phone: 551126616293, Email: marciasqz@gmail.com

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 3, 6, 9 and 12 months after the study start. During routine medical appointments will be analyzed self- monitoring of capillary blood glucose (SMBG) and the hypoglycemia score. After six months 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 6 and 12 months. 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.

Official title: Subcutaneous Insulin Glargine Versus NPH Insulin in Patients With Chronic Kidney Disease Stages III and IV: Randomized Controlled Trial.

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in Glycated Hemoglobin (A1c)

Secondary outcome: hypoglycemia

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 3, 6, 9 and 12 months 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 six months 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 six months 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.

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients with type 2 diabetes mellitus and chronic kidney disease secondary to

diabetic nephropathy in stages 3 and 4 (moderate and severe nephropathy, corresponding to glomerular filtration rate of 15-59 ml/min/1. 73m²) will be included in the study. Exclusion Criteria:

- Patients with systemic neoplasias,

- HIV, chronic kidney disease or nephropathy from other etiologies,

- severe psychiatric disorders

- pregnant women.

Marcia Queiroz, PhD, Phone: 551126616293, Email: marciasqz@gmail.com

University of Sao Paulo, Sao Paulo 05410001, Brazil; Recruiting
Marcia Queiroz, PhD, Phone: 551126616293, Email: marciasqz@gmail.com
Marcia Queiroz, PhD, Principal Investigator
Silvia Titan, PhD, Principal Investigator
Carolina Betonico, MD, Sub-Investigator

Starting date: December 2013
Last updated: May 25, 2015