Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls - Full Text View

Sponsor:	Indiana University
Information provided by:	Indiana University
ClinicalTrials.gov Identifier:	NCT00837590

Purpose

We intend to pursue the following Aims:

Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity?
Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin?
Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril?

The intent of the current project is to efficiently and at low cost generate preliminary data along each of these lines of questioning, studying the minimum number of subjects required to assess the viability of the question using the current measurement approaches.

Condition	Intervention
Pre-diabetes Obesity	Drug: salsalate Drug: metformin Drug: lisinopril

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls

Resource links provided by NLM:

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

MedlinePlus related topics: Diabetes Medicines Obesity Pre-diabetes

Drug Information available for: Sodium salicylate Lisinopril Salicylsalicylic acid Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Indiana University:

Primary Outcome Measures:

The primary endpoints of interest are basal flow and diameter, flow-mediated vasodilation, insulin-stimulated glucose disposal and insulin-mediated vasodilation measured by brachial artery ultrasound [ Time Frame: End of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Other endpoints of interest include circulating levels of endothelin and nitric oxide, levels of inflammatory markers, circulating endothelial progenitor cell numbers, and steady-state glucose disposal rate for the insulin infusion study. [ Time Frame: End of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	March 2009
Study Completion Date:	August 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Nondiabetic lean and obese subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months of treatment with salsalate.	Drug: salsalate Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.
Experimental: Metformin Obese subjects will be pre-treated with metformin 1000mg bid for 4 weeks prior to baseline measurements and will continue metformin in addition to salsalate for an additional 2 months.	Drug: salsalate Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses. Drug: metformin metformin po 1000mg bid
Experimental: Lisinopril Obese subjects will be pre-treated with lisinopril 20mg qd for 4 weeks prior to baseline measurements and continue lisinopril in addition to salsalate for an additional 2 months.	Drug: salsalate Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses. Drug: lisinopril lisinopril po 20mg qd

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

healthy
normotensive (BP<140/95 mmHg)
lean and obese
18 and 55 years
women must be premenopausal

Exclusion Criteria:

use of pharmacologic agents or recreational drugs, with the exception of occasional use of non-narcotic pain medications
blood pressure (>140/90 mmHg)
elevated cholesterol (LDL >130 mg/dL)
diabetes mellitus (by ADA criteria)
evidence of coronary and/or peripheral vascular disease by history and physical exam
>5 kg change in weight in the preceding 3 months
chronic systemic illness with recognized metabolic effects
hepatitis C and HIV
recognized systemic inflammatory or autoimmune processes such as rheumatoid arthritis or systemic lupus erythematosis
Raynaud's phenomenon or other abnormalities of hand or finger perfusion
regular participation in endurance or high-performance athletic activity
history of aspirin or salsalate sensitivity including aspirin-induced asthma
prior treatment with salsalate, pentoxyfilline, or monoclonal anti-TNFalpha antibodies
pregnancy
liver transaminase levels >3 times the upper limit of normal
creatinine >1.5 mg/dL
history of a cellular immunodeficiency-related opportunistic infections, such as an endemic mycosis (eg. histoplasmosis) or mycobacterial infection (eg tuberculosis)
reactive tuberculin skin test
history of malignancy except for basal cell carcinoma of the skin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00837590

Locations

United States, Indiana
Indiana Clinical Research Center
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

Investigators

Principal Investigator:

Kieren J Mather, MD

Indiana University

More Information

No publications provided

Responsible Party:	Kieren Mather, MD, Indiana University
ClinicalTrials.gov Identifier:	NCT00837590 History of Changes
Other Study ID Numbers:	IU-IRB-0901-03
Study First Received:	February 4, 2009
Last Updated:	October 29, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Indiana University:

Vascular function
Glucose tolerance
Obesity
Pre-diabetes

Additional relevant MeSH terms:

Diabetes Mellitus
Inflammation
Obesity
Glucose Intolerance
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia

Metformin
Sodium Salicylate
Salicylsalicylic acid
Lisinopril
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on February 12, 2012