Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes
This study has been completed.
Sponsor:
Dana King
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Dana King, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00770367
First received: October 9, 2008
Last updated: December 2, 2011
Last verified: December 2011
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Purpose
SPECIFIC AIMS
- To determine whether pioglitazone will reduce levels of asymmetric dimethylarginine(ADMA) in patients with diabetes.
- To determine whether nitric oxide(NOx) products are increased with pioglitazone treatment.
- To determine whether pioglitazone reduces oxidative stress (F2-isoprostanes).
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes |
Drug: Pioglitazone then Placebo Drug: Placebo then Pioglitazone |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes |
Resource links provided by NLM:
Further study details as provided by Medical University of South Carolina:
Primary Outcome Measures:
- Asymmetric Dimethylarginine (ADMA) Level [ Time Frame: 3 months ] [ Designated as safety issue: No ]Labs measured micro moles per liter of ADMA levels in participants.
Secondary Outcome Measures:
- NOx f2-isoprostanes [ Time Frame: 3 months ] [ Designated as safety issue: No ]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
| Enrollment: | 36 |
| Study Start Date: | October 2008 |
| Study Completion Date: | June 2010 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
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.
Other Name: Actos, Glustin, Zactos
|
|
Experimental: 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.
|
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.
Other Name: Actos, Glustin, Zactos
|
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.
Eligibility| Ages Eligible for Study: | 40 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00770367
Locations
| United States, South Carolina | |
| Department of Family Medicine, MUSC | |
| Charleston, South Carolina, United States, 29425 | |
Sponsors and Collaborators
Dana King
Takeda Pharmaceuticals North America, Inc.
Investigators
| Principal Investigator: | Dana E King, MD | MUSC |
More Information
No publications provided
| Responsible Party: | Dana King, Vice Chair and Proffessor, Medical University of South Carolina |
| ClinicalTrials.gov Identifier: | NCT00770367 History of Changes |
| Other Study ID Numbers: | Takeda 07-060, 18379 |
| Study First Received: | October 9, 2008 |
| Results First Received: | July 8, 2010 |
| Last Updated: | December 2, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Medical University of South Carolina:
|
Cardiovascular risk biological markers |
Additional relevant MeSH terms:
|
Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases N,N-dimethylarginine Pioglitazone |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Hypoglycemic Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 22, 2013