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

NCT00837590 | Terminated Phase 1 Results DMC

• 1 other identifier: IU-IRB-0901-03
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Aims:

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

Conditions

Pre-diabetes; Obesity

Keywords

Vascular function; Glucose tolerance; Obesity; Pre-diabetes

Outcome Measures

Primary Outcomes (1)

• Vascular Function

  The primary endpoints of interest is flow-mediated vasodilation

  Measured at baseline and after a single oral dose of salsalate (Acute) or 2 months' treatment with salsalate (Chronic)

Study Arms (3)

Acute Salsalate

EXPERIMENTAL

Nondiabetic lean and obese subjects will be studied in this arm. Subjects will be studied at baseline and after a single dose of oral salsalate.

Drug: Acute Salsalate

Chronic Salsalate - Obese

EXPERIMENTAL

Obese subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months' treatment with oral salsalate.

Drug: Chronic salsalate

Chronic Salsalate - Lean

EXPERIMENTAL

Lean subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months' treatment with oral salsalate. The effects of an acute fatty acid infusion on vascular function will be measured on both occasions.

Drug: Chronic salsalate

Interventions

Chronic salsalate DRUG

Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.

Chronic Salsalate - Lean; Chronic Salsalate - Obese

Acute Salsalate DRUG

Subjects will receive a single oral dose of 2 gram of oral salsalate

Acute Salsalate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana Clinical Research Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Glucose Intolerance; Obesity

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was a small pilot not powered for main outcomes; the goal was to gather preliminary data for future grants.

Results Point of Contact

• Title: Dr. Kieren Mather
• Organization: Indiana University

kmather@iupui.edu

317-278-2187

Study Officials

• Kieren J Mather, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2009
• First Posted: February 5, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: August 1, 2010
• Last Updated: August 1, 2019
• Results First Posted: August 1, 2019

Record last verified: 2013-05

Locations

US (1)