Efficacy of Pioglitazone on Microcirculation in Type 2 Diabetes Patients Treated With Insulin - Full Text View

Sponsor:	Takeda Global Research & Development Centre (Europe) Ltd.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00676260

Purpose

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	Intervention	Phase
Diabetes Mellitus	Drug: Pioglitazone Drug: Placebo	Phase II

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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Insulin Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Capillary filtration capacity. [ Time Frame: Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Isovolumetric venous pressure. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Capillary pressure. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Postural vasoconstriction. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Maximum blood flow. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Capillary recruitment. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
24-hour ambulatory blood pressure. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Interleukin-6 [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
C-Reactive Protein. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]
Vascular Endothelium Growth Factor. [ Time Frame: Final Visit ] [ Designated as safety issue: Yes ]

Enrollment:	29
Study Start Date:	December 2002
Study Completion Date:	August 2004
Primary Completion Date:	August 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00676260

Locations

United Kingdom

Exeter, United Kingdom

Sponsors and Collaborators

Takeda Global Research & Development Centre (Europe) Ltd.

Investigators

Study Director:

Medical Director

Takeda Global Research & Development Centre (Europe) Ltd.

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

Publications:

Tooke JE, Elston LM, Gooding KM, Ball CI, Mawson DM, Piper J, Sriraman R, Urquhart R, Shore AC. The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin. Diabetologia. 2006 May;49(5):1064-70. Epub 2006 Mar 1.

Responsible Party:	VP, Clinical Science, Takeda Global Research & Development Centre (Europe) Ltd.
ClinicalTrials.gov Identifier:	NCT00676260 History of Changes
Other Study ID Numbers:	AD4833/EC412, U1111-1114-1082
Study First Received:	May 9, 2008
Last Updated:	July 1, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory 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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012