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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 Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:
NCT00770640
First received: October 9, 2008
Last updated: August 31, 2010
Last verified: August 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
 Drug: Pioglitazone and insulin
Drug: Insulin
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:
  • Change of total daily Insulin Dose. [ Time Frame: Week 24 or Final Visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 40
Study Start Date: August 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 30mg QD
(and variable insulin therapy)
 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
Placebo Comparator: Placebo QD
(and variable insulin therapy)
 Drug: Insulin
Pioglitazone placebo-matching tablets, orally, once daily and variable insulin therapy for up to 24 weeks.

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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00770640

Locations
Germany
Schwetzingen, Baden-Württemberg, Germany
Wiesbaden, Hessen, Germany
Bottrop, Nordrhein-Westfalen, Germany
Düsseldorf, Nordrhein-Westfalen, Germany
Lüdenscheid, Nordrhein-Westfalen, Germany
Solingen, Nordrhein-Westfalen, Germany
Alzey, Rheinland-Pfalz, Germany
Ingelheim, Rheinland-Pfalz, Germany
Mainz, Rheinland-Pfalz, Germany
Sponsors and Collaborators
Takeda Pharma GmbH
Investigators
Study Director: Medical Director Takeda Pharma GmbH
  More Information

Additional Information:
ACTOS® Package Insert  This link exits the ClinicalTrials.gov site
FDA Safety Alerts and Recalls  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Medical Director, Takeda Pharma GmbH, Aachen (Germany)
ClinicalTrials.gov Identifier: NCT00770640     History of Changes
Other Study ID Numbers: ATS K029, 2007-006744-21, DE-PIO-029, U1111-1114-1645
Study First Received: October 9, 2008
Last Updated: August 31, 2010
Health Authority: European Union: European Medicines Agency

Keywords provided by Takeda Global Research & Development Center, Inc.:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
 Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Renal Insufficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
 Urologic Diseases
Pioglitazone
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013