Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes

NCT ID: NCT00770367

Last Updated: 2018-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2010-06-30

Brief Summary

SPECIFIC AIMS

1. To determine whether pioglitazone will reduce levels of asymmetric dimethylarginine(ADMA) in patients with diabetes.

2. To determine whether nitric oxide(NOx) products are increased with pioglitazone treatment.

3. To determine whether pioglitazone reduces oxidative stress (F2-isoprostanes).

Detailed Description

The primary purpose of this study is to determine whether treatment with pioglitazone can reduce serum levels of asymmetric dimethylarginine (ADMA) in patients with adult diabetes. Recent research has found that elevated serum ADMA is associated with increased cardiovascular events and mortality, particularly in people with diabetes (Boger 2005, Zoccali 2006, Ueda 2007). ADMA, by mediating nitric oxide (NO) availability, may trigger pro-atherogenic effects. High plasma concentration of this substance has been associated with intima-media thickening, left ventricular hypertrophy and all-cause and cardiovascular mortality in patients with end-stage renal disease, and associated with increased cardiovascular events in patients with diabetes (Kryzazanowska 2007). The result of higher levels of ADMA and reduced output of NO increases vasoconstriction, increases inflammation, and interferes with endothelial function. Preliminary studies indicate that pioglitazone may reduce ADMA levels, and thus lower cardiovascular risk.Thus, this protocol will test whether pioglitazone can reduce ADMA levels in adult patients with diabetes.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pioglitazone then Placebo

18 volunteers that are Diabetic adults, 40-75 years that have higher ADMA levels as well as increased inflammation will take Pioglitazone for the first 12 week period of the study and then take the placebo for the final 12 weeks of the study.

Group Type: EXPERIMENTAL

Pioglitazone then Placebo

Intervention Type: DRUG

Subjects will take the pioglitazone 30mg tablet daily for 3 months. This will be followed by a 4-week period during which subjects will not be taking either the study drug or placebo. During the final 12-week period the group will take a placebo.

Placebo then Pioglitazone

18 (other half of participants) volunteers that are Diabetic adults, 40-75 years that have higher ADMA levels as well as increased inflammation will take the placebo for the first 12 week period of the study and then take the Pioglitazone for the final 12 weeks of the study.

Group Type: EXPERIMENTAL

Placebo then Pioglitazone

Intervention Type: DRUG

Subjects will take the placebo for the first 12 weeks of the study. This will be followed by a 4-week period during which subjects will not be taking either the study drug or placebo. During the final 12-week period the group will take the pioglitazone 30mg tablet daily for 3 months.

Interventions

Pioglitazone then Placebo

Subjects will take the pioglitazone 30mg tablet daily for 3 months. This will be followed by a 4-week period during which subjects will not be taking either the study drug or placebo. During the final 12-week period the group will take a placebo.

Intervention Type: DRUG

Placebo then Pioglitazone

Subjects will take the placebo for the first 12 weeks of the study. This will be followed by a 4-week period during which subjects will not be taking either the study drug or placebo. During the final 12-week period the group will take the pioglitazone 30mg tablet daily for 3 months.

Intervention Type: DRUG

Other Intervention Names

Actos, Glustin, Zactos; Actos, Glustin, Zactos

Eligibility Criteria

Inclusion Criteria

• Adults age 40--75 years-of-age, non-pregnant
• Informed consent
• History of type 2 Diabetes Mellitus
• Stable weight for the last 3 months (no change greater than +5% of body weight)
• ADMA > 0.50 µM/L (mean of non-diabetic reference group) (Devangelio 2007)
• On stable medical therapy for at least 3 months
• A working telephone

Exclusion Criteria

• Any history of known coronary heart disease, including a history of congestive heart failure, myocardial infarction, coronary re-vascularization, or stroke
• Pregnancy
• Chronic kidney disease, serum creatinine >2.0mg/dl, chronic liver disease, or uncontrolled hypertension (>160/100).
• Current participation in a formal weight loss program or planning to start such a program during the next 3 months
• Collagen vascular disease, infection, or other inflammatory condition
• Electrocardiogram (EKG) evidence of ischemia or infarction
• Macular edema (swelling of the back of the eye), recent excessive weight gain (over 5% of weight in 30 days), elevated liver function tests > 2.5 X the upper limit, or history of osteoporosis

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dana E King, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Department of Family Medicine, MUSC

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

18379

Identifier Type: OTHER

Identifier Source: secondary_id

Takeda 07-060

Identifier Type: -

Identifier Source: org_study_id