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

Primary Purpose

Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Pioglitazone and insulin
Insulin
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pioglitazone 30mg QD

Placebo QD

Arm Description

(and variable insulin therapy)

(and variable insulin therapy)

Outcomes

Primary Outcome Measures

Change of total daily Insulin Dose.

Secondary Outcome Measures

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.

Full Information

First Posted
October 9, 2008
Last Updated
August 31, 2010
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT00770640
Brief Title
Efficacy of Pioglitazone and Insulin in Treating Subjects With Type 2 Diabetes Mellitus and Renal Failure.
Acronym
PIOren
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 Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Takeda

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pioglitazone 30mg QD
Arm Type
Experimental
Arm Description
(and variable insulin therapy)
Arm Title
Placebo QD
Arm Type
Placebo Comparator
Arm Description
(and variable insulin therapy)
Intervention Type
Drug
Intervention Name(s)
Pioglitazone and insulin
Other Intervention Name(s)
ACTOS®, AD-4833
Intervention Description
Pioglitazone 30 mg, tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
Pioglitazone placebo-matching tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
Primary Outcome Measure Information:
Title
Change of total daily Insulin Dose.
Time Frame
Week 24 or Final Visit.
Secondary Outcome Measure Information:
Title
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.
Title
Change from Baseline in Glycosylated Hemoglobin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Glucose.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Insulin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in C-peptide.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Intact Proinsulin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Adiponectin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Angiotensin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Relaxin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in fetuin A.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Carbonyl Protein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Myeloperoxidase.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Matrix-Gla Protein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in High Sensitivity C-reactive Protein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Cholesterol.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in High-Density Lipoprotein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Low-Density Lipoprotein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Oxidized Low-Density Lipoprotein.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Triglycerides.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Matrix Metalloproteinase -9.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in Monocyte Chemoattractant Protein -1.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Change from Baseline in E-selectin.
Time Frame
Weeks 12 and 24 or Final Visit.
Title
Pioglitazone in serum.
Time Frame
Week 12.
Title
Change from Baseline in intact Parathyroid Hormone.
Time Frame
Weeks 12 and 24 or Final Visit.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Takeda Pharma GmbH, Aachen (Germany)
Official's Role
Study Director
Facility Information:
City
Schwetzingen
State/Province
Baden-Württemberg
Country
Germany
City
Wiesbaden
State/Province
Hessen
Country
Germany
City
Bottrop
State/Province
Nordrhein-Westfalen
Country
Germany
City
Düsseldorf
State/Province
Nordrhein-Westfalen
Country
Germany
City
Lüdenscheid
State/Province
Nordrhein-Westfalen
Country
Germany
City
Solingen
State/Province
Nordrhein-Westfalen
Country
Germany
City
Alzey
State/Province
Rheinland-Pfalz
Country
Germany
City
Ingelheim
State/Province
Rheinland-Pfalz
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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