Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes - Full Text View

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

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:

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

MedlinePlus related topics: Diabetes

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

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 23, 2012