Official Title: “Effect of Pioglitazone 15 mg or 30 mg on Microcirculation in Type 2 Diabetes Patients Treated With Insulin”

This was a randomized, double-blind, parallel group, placebo controlled comparison study designed to identify the mechanisms underlying peripheral edema formation with pioglitazone.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2004

The study comprised five visits over a period of 10-12 weeks, including an 8-10 week treatment with pioglitazone HCl 15 mg QD (which could be titrated up to 30 mg QD at Week 2 or Week 4). Study procedures included capillary filtration capacity, isovolumetric pressure, capillary pressure, postural vasoconstriction, maximum blood flow, capillary recruitment, 24-hour ambulatory blood pressure monitoring, Interleukin-6, C-reactive protein, and vascular endothelium growth factor, which were performed at Baseline and Week 8. Other procedures and safety monitoring were also carried out during the course of the study.

Intervention(s) in this Clinical Trial

• Drug: pioglitazone HCl
  • Oral tablet
• Drug: Placebo
  • Oral tablet

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Pioglitazone HCl, provided orally at 15 mg QD to Type 2 diabetes patients receiving insulin with or without metformin. Dose could be titrated to 30 mg QD (Week 2) on the basis of tolerability and blood glucose levels. The dose could be reduced again at any time.
• Placebo Comparator: 2
  • Placebo, provided orally to Type 2 diabetes patients receiving insulin with or without metformin.

Primary Measures

• Capillary filtration capacity.
  • Time Frame: 8-10 Weeks.
    Safety Issue?: No

Secondary Measures

• Isovolumetric venous pressure, capillary pressure, postural vasoconstriction, maximum blood flow, capillary recruitment, 24-hour ambulatory blood pressure, IL-6, CRP, VEGF, HbA1C and fasting plasma glucose.
  • Time Frame: 8-10 Weeks.
    Safety Issue?: Yes
• Triglycerides. Safety variables including vital signs, clinical laboratory tests (hematology, blood chemistry, and urinalysis), ECG, physical examination, body weight, and adverse events.
  • Time Frame: 8-10 Weeks.
    Safety Issue?: Yes

Inclusion Criteria:

• Men or women between 40 and 80 years of age.
• Stable glycemic control in the two months prior to the study.
• Type 2 diabetes treated by diet and stable doses of insulin (alone or with metformin) in the three months prior to the study.
• Female patients must have been postmenopausal, had a hysterectomy, or were surgically sterilized.

Exclusion Criteria:

• Subject had Type 1 diabetes.
• Subject had an episode of hypoglycemia requiring medical assistance three months prior to the study.
• Subject had peripheral artery disease (including Raynaud's syndrome) confirmed by an Ankle Brachial Pressure Index less than 0.9.
• Subject had sever chronic venous insufficiency as evidenced by venous ulceration or subcutaneous serum deposits.
• Subject had vascular autoimmune disease, had received a renal transplant, or were receiving dialysis.
• Subject had heart failure (NYHA I to IV), left ventricular hypertrophy evident from the ECG, or myocardial infarction 12 months prior to start of study.
• Subject had uncontrolled hypertension or familial polyposis coli.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

Richard Urquhart, MD Study Director Takeda Europe Research & Development Centre Ltd.  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00676260

Study ID Number: AD-4833/EC412

ClinicalTrials.gov Identifier: NCT00676260

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency