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Efficacy of Pioglitazone on Microcirculation in Type 2 Diabetes Patients Treated With Insulin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00676260
Recruitment Status : Completed
First Posted : May 13, 2008
Last Update Posted : February 28, 2012
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to measure microcirculation in type 2 diabetes patients with peripheral edema who are taking pioglitazone, once daily (QD).

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Drug: Pioglitazone Drug: Placebo Phase 2

Detailed Description:

Pioglitazone is a thiazolidinedione compound with a mode of action as a peroxisome proliferator-activated receptor gamma agonist. Activation of this receptor causes increased transcriptional activity at a number of locations that are important to carbohydrate and lipid (fat) metabolism. Insulin resistance is reversed by enhancing the action of insulin, thereby promoting glucose utilization in peripheral tissues, suppressing gluconeogenesis in the liver, and reducing lipolysis at the adipocyte.

In previous studies of pioglitazone, peripheral edema (swelling in the hands, feet, and legs) was reported as an adverse event more often in pioglitazone groups and appears to be a dose dependent phenomenon with pioglitazone. The incidence of peripheral edema in monotherapy studies was 3.2% in pioglitazone patients compared with 0.7% placebo patients and was reported more by females than males. This incidence was higher when pioglitazone was combined with sulphonylurea or insulin (5.9% and 15.6%, respectively). In comparison, the incidence of edema, when sulphonylurea or insulin was combined with placebo, was 2.1% and 7.5%, respectively.

This study is designed to identify the mechanisms underlying peripheral edema formation with pioglitazone in patients with Type 2 diabetes.

Individuals who participate in this study will provide written informed consent and will be required to commit to a screening visit and approximately 4 additional visits at the study center. Study participation is anticipated to be about 10 to 12 weeks (or approximately 3 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Pioglitazone 15 mg or 30 mg on Microcirculation in Type 2 Diabetes Patients Treated With Insulin
Study Start Date : December 2002
Actual Primary Completion Date : August 2004
Actual Study Completion Date : August 2004

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pioglitazone QD Drug: Pioglitazone
Pioglitazone 15 mg to 30 mg, tablets, orally, once daily for up to 10 weeks
Other Names:
  • Actos
  • AD4833

Placebo Comparator: Placebo QD Drug: Placebo
Pioglitazone placebo-matching tablets, orally, once daily for up to 10 weeks

Primary Outcome Measures :
  1. Capillary filtration capacity. [ Time Frame: Final Visit ]

Secondary Outcome Measures :
  1. Isovolumetric venous pressure. [ Time Frame: Final Visit ]
  2. Capillary pressure. [ Time Frame: Final Visit ]
  3. Postural vasoconstriction. [ Time Frame: Final Visit ]
  4. Maximum blood flow. [ Time Frame: Final Visit ]
  5. Capillary recruitment. [ Time Frame: Final Visit ]
  6. 24-hour ambulatory blood pressure. [ Time Frame: Final Visit ]
  7. Interleukin-6 [ Time Frame: Final Visit ]
  8. C-Reactive Protein. [ Time Frame: Final Visit ]
  9. Vascular Endothelium Growth Factor. [ Time Frame: Final Visit ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Stable glycemic control glycosylated hemoglobin between 6.5 and 10%) in the two months prior to the study.
  • Type 2 diabetes treated by diet and stable dose 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:

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

    • Non steroidal anti-inflammatory Drugs (except for aspirin at anti-aggregant doses), oral anti-diabetic drugs (except metformin), calcium-channel blockers, and diuretics at anti-edema doses are excluded from the study.
    • Treatment with systemic corticosteroids within four weeks prior to enrolment and during the study was not allowed.
    • Patients who have taken beta-blockers are to have been on a stable dose for four weeks before entry in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00676260

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United Kingdom
Exeter, United Kingdom
Sponsors and Collaborators
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Study Director: Medical Director Takeda
Additional Information:
Publications of Results:
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Responsible Party: Takeda Identifier: NCT00676260    
Other Study ID Numbers: AD4833/EC412
U1111-1114-1082 ( Registry Identifier: WHO )
First Posted: May 13, 2008    Key Record Dates
Last Update Posted: February 28, 2012
Last Verified: February 2012
Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Drug Therapy
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs