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

Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00770367
• Other study ID #: Takeda 07-060
• Secondary ID: 18379
• Status: Completed
• Phase: Phase 4
• Start date: October 2008
• Est. completion date: June 2010

Study information

• Verified date: December 2011
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Department of Family Medicine, MUSC	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Asymmetric Dimethylarginine (ADMA) Level	Labs measured micro moles per liter of ADMA levels in participants.	3 months
Secondary	NOx f2-isoprostanes	Measured oxidative stress - NOx measured by chemiluminescence detection using the Sievers NOA 280i and f2-isoprostanes are isolated by thin layer chromatography and subjected to a highly sensitive and specific gas chromatography/mass spectroscopy method to measusre the oxidative stress	3 months