Efficacy of Pioglitazone and Insulin in Treating Subjects With Type 2 Diabetes Mellitus and Renal Failure.

Condition(s) targeted: Diabetes Mellitus

Intervention: Pioglitazone and insulin (Drug); Insulin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Takeda Pharma GmbH

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Takeda Pharma GmbH

Overall contact:
Study Manager, Phone: +49 800 8253325

The purpose of this study is to determine the metabolic and cardiovascular effects of pioglitazone and insulin combination therapy in subjects with Type 2 Diabetes and Renal Failure.

Official title: Comparison of the Effects of Pioglitazone vs. Placebo When Given in Addition to Standard Insulin Treatment in Patients With Type 2 Diabetes Mellitus and Renal Failure

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change of total daily Insulin Dose.

Secondary outcome:

Individual insulin doses to assess the number of patients with insulin reduction of greater than or equal to 30%.

Change from Baseline in Glycosylated Hemoglobin.

Change from Baseline in Glucose.

Change from Baseline in Insulin.

Change from Baseline in C-peptide.

Change from Baseline in Intact Proinsulin.

Change from Baseline in Adiponectin.

Change from Baseline in Angiotensin.

Change from Baseline in Relaxin.

Change from Baseline in fetuin A.

Change from Baseline in Carbonyl Protein.

Change from Baseline in Myeloperoxidase.

Change from Baseline in Matrix-Gla Protein.

Change from Baseline in High Sensitivity C-reactive Protein.

Change from Baseline in Cholesterol.

Change from Baseline in High-Density Lipoprotein.

Change from Baseline in Low-Density Lipoprotein.

Change from Baseline in Oxidized Low-Density Lipoprotein.

Change from Baseline in Triglycerides.

Change from Baseline in Matrix Metalloproteinase -9.

Change from Baseline in Monocyte Chemoattractant Protein -1.

Change from Baseline in E-selectin.

Pioglitazone in serum.

Change from Baseline in intact Parathyroid Hormone.

Detailed description: Patients with type 2 diabetes mellitus and clinically significant kidney disease presenting with contra-indications for metformin and sulfonylurea drugs are usually treated with insulin therapy only. While the prolonged pharmacokinetic insulin profile due to delayed renal insulin elimination already is a hurdle for a successful therapy, impaired kidney function results in increased oxidative stress and cardiovascular risk, especially in patients requiring dialysis. Several potential mechanisms may explain this increased cardiovascular risk, and one, frequent finding is coexistence of several other independent cardiovascular risk factors including dyslipidemia, hypertension and smoking. In addition, impaired kidney function is associated with elevated markers of inflammation and other putative risk factors for cardiovascular events.

The focus of this study is to investigate whether pioglitazone may help improve overall metabolic and cardiovascular risks in patients with end stage renal disease, and if pioglitazone can potentially exert positive effects on kidney function in patients with renal failure requiring dialysis.

The duration of treatment for patients completing the study is approximately 26 weeks.

Minimum age: 30 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Has Type 2 Diabetes Mellitus, and is a patient on insulin treatment for at least 3

months.

- Has a body mass index less than 36 kg/m²

- Has a glycosylated hemoglobin level of 6. 5 % and less than 10 %.

- Patient is on hemo-dialysis with or without residual excretion

- An insulin dose greater than 20 IE/day

Exclusion Criteria:

- Has a history of type 1 diabetes.

- Has acute infections.

- History of hypersensitivity to the study drugs or to drugs with similar chemical

structures.

- History of severe or multiple allergies.

- Has a progressive fatal disease other than kidney failure.

- Has a history of drug or alcohol abuse within the last 5 years.

- A history of significant cardiovascular (e. g. Coronary heart failure based on New

York Heart Association stage III - IV), respiratory, gastrointestinal, hepatic (e. g.

alanine aminotransferase greater than 2. 5 times the normal reference range) or hematological disease.

- History of primary hyperaldosteronism

- Acute myocardial infarction, open heart surgery or cerebral event (stroke/transient

ischemic attack) within the last year prior to study start.

- Any further antidiabetic treatment except pioglitazone and insulin.

- History of macular edema.

- Is required to take or intends to continue taking any disallowed medication, any

prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

- Treatment with any other investigational drug within 3 months before trial

entry.

- Treatment with steroids within 3 months before trial entry.

- Treatment with thiazolidinediones within the past 3 months.

- If statin therapy applicable: Change of medication within the last 4 weeks.

- Pre-treatment with gemfibrozil within the last 12 weeks.

- Pre-treatment with rifampicin within the last 12 weeks.

- Has uncontrolled unstable angina.

Study Manager, Phone: +49 800 8253325

Schwetzingen, Baden-Württemberg, Germany; Recruiting

Wiesbaden, Hessen, Germany; Recruiting

Lüdenscheid, Nordrhein-Westfalen, Germany; Recruiting

Solingen, Nordrhein-Westfalen, Germany; Recruiting

Bottrop, Nordrhein-Westfalen, Germany; Recruiting

Düsseldorf, Nordrhein-Westfalen, Germany; Recruiting

Mainz, Rheinland-Pfalz, Germany; Recruiting

Ingelheim, Rheinland-Pfalz, Germany; Recruiting

Alzey, Rheinland-Pfalz, Germany; Recruiting

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FDA Safety Alerts and Recalls

Starting date: August 2008
Ending date: April 2010
Last updated: August 20, 2009