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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00676260
First received: May 9, 2008
Last updated: February 27, 2012
Last verified: February 2012
  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 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: Effect of Pioglitazone 15 mg or 30 mg on Microcirculation in Type 2 Diabetes Patients Treated With Insulin

Resource links provided by NLM:


Further study details as provided by Takeda:

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
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, see Learn About Clinical Studies.

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

Locations
United Kingdom
Exeter, United Kingdom
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00676260     History of Changes
Other Study ID Numbers: AD4833/EC412, U1111-1114-1082
Study First Received: May 9, 2008
Last Updated: February 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Lipoatrophic
Dyslipidemia
Drug Therapy

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

ClinicalTrials.gov processed this record on October 22, 2014