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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00770640
First received: October 9, 2008
Last updated: August 31, 2010
Last verified: August 2010

October 9, 2008
August 31, 2010
August 2008
June 2010   (final data collection date for primary outcome measure)
Change of total daily Insulin Dose. [ Time Frame: Week 24 or Final Visit. ] [ Designated as safety issue: No ]
The change of total daily insulin dose. [ Time Frame: End of Treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00770640 on ClinicalTrials.gov Archive Site
  • Individual insulin doses to assess the number of patients with insulin reduction of greater than or equal to 30%. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Glucose. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Insulin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in C-peptide. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Intact Proinsulin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Adiponectin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Angiotensin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Relaxin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in fetuin A. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Carbonyl Protein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Myeloperoxidase. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Matrix-Gla Protein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in High Sensitivity C-reactive Protein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Cholesterol. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in High-Density Lipoprotein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Low-Density Lipoprotein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Oxidized Low-Density Lipoprotein. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Triglycerides. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Matrix Metalloproteinase -9. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in Monocyte Chemoattractant Protein -1. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Change from Baseline in E-selectin. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Pioglitazone in serum. [ Time Frame: Week 12. ] [ Designated as safety issue: No ]
  • Change from Baseline in intact Parathyroid Hormone. [ Time Frame: Weeks 12 and 24 or Final Visit. ] [ Designated as safety issue: No ]
  • Individual insulin doses to assess the number of patients with insulin reduction of greater than or equal to 30%. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Glucose Laboratory marker. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Laboratory markers (insulin, C-peptide and intact proinsulin). [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Laboratory markers (adiponectin and angiotensin). [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Laboratory markers (relaxin, fetuin A and carbonyl protein). [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Calcification Markers (Myeloperoxidase and matrix-gla protein). [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in High sensitivity C-reactive protein. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Lipids (cholesterol, high-density lipoprotein, low-density lipoprotein, oxidized low-density lipoprotein and triglycerides). [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Matrix Metalloproteinase -9 and Monocyte Chemoattractant Protein -1. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in E-selectin. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
  • Pioglitazone in serum. [ Time Frame: Week: 12. ] [ Designated as safety issue: No ]
  • The change from Baseline in intact Parathyroid Hormone. [ Time Frame: Weeks: 12 and 24. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy of Pioglitazone and Insulin in Treating Subjects With Type 2 Diabetes Mellitus and Renal Failure.
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

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus
  • Drug: Pioglitazone and insulin
    Pioglitazone 30 mg, tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
    Other Names:
    • ACTOS®
    • AD-4833
  • Drug: Insulin
    Pioglitazone placebo-matching tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
  • Experimental: Pioglitazone 30mg QD
    (and variable insulin therapy)
    Intervention: Drug: Pioglitazone and insulin
  • Placebo Comparator: Placebo QD
    (and variable insulin therapy)
    Intervention: Drug: Insulin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
June 2010
June 2010   (final data collection date for primary outcome measure)

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 greater than or equal to 6.0% 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.
Both
30 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00770640
ATS K029, 2007-006744-21, DE-PIO-029, U1111-1114-1645
No
Medical Director, Takeda Pharma GmbH, Aachen (Germany)
Takeda
Not Provided
Study Director: Medical Director Takeda Pharma GmbH, Aachen (Germany)
Takeda
August 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP