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

Sponsor:	Medical University of South Carolina
Collaborator:	Takeda Global Research & Development Center, Inc.
Information provided by:	Medical University of South Carolina
ClinicalTrials.gov Identifier:	NCT00770367

Purpose

SPECIFIC AIMS

To determine whether pioglitazone will reduce levels of ADMA in patients with diabetes.
To determine whether nitric oxide products (NOx) are increased with pioglitazone treatment.
To determine whether pioglitazone reduces oxidative stress (F2-isoprostanes).

Condition	Intervention	Phase
Diabetes	Drug: pioglitazone	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes

Resource links provided by NLM:

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:

ADMA level [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

NOx f2-isoprostanes [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
pioglitazone: Experimental	Drug: pioglitazone pioglitazone 30mg daily for 3 months

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
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

Contacts

Contact: Dana E King, MD	843-792-5262	kingde@musc.edu
Contact: Lynne hartel	843-792-8385	hartel@musc.edu

Locations

United States, South Carolina
Department of Family Medicine, MUSC	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Lynne Hartel 843-792-8385 hartel@musc.edu
Contact: Tara Hogue 843-792-8112 hoguetm@musc.edu
Principal Investigator: Dana E King, MD
Sub-Investigator: Marty Player, MD

Sponsors and Collaborators

Medical University of South Carolina

Takeda Global Research & Development Center, Inc.

Investigators

Principal Investigator:

Dana E King, MD

MUSC

More Information

No publications provided

Responsible Party:	Medical University of South Carolina ( Dana E. King MD )
Study ID Numbers:	Takeda 07-060, 18379
Study First Received:	October 9, 2008
Last Updated:	October 9, 2008
ClinicalTrials.gov Identifier:	NCT00770367 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Medical University of South Carolina:

Cardiovascular risk
biological markers

Additional relevant MeSH terms:

Hypoglycemic Agents
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Pioglitazone
Physiological Effects of Drugs
Diabetes Mellitus

Endocrine System Diseases
Enzyme Inhibitors
Glucose Metabolism Disorders
N,N-dimethylarginine
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010