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

Primary Purpose

Pre-diabetes, Obesity

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Chronic salsalate
Acute Salsalate
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pre-diabetes focused on measuring Vascular function, Glucose tolerance, Obesity, Pre-diabetes

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Indiana Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Acute Salsalate

Chronic Salsalate - Obese

Chronic Salsalate - Lean

Arm Description

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.

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

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.

Outcomes

Primary Outcome Measures

Vascular Function
The primary endpoints of interest is flow-mediated vasodilation

Secondary Outcome Measures

Full Information

First Posted
February 4, 2009
Last Updated
June 5, 2019
Sponsor
Indiana University
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1. Study Identification

Unique Protocol Identification Number
NCT00837590
Brief Title
Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls
Official Title
Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Why Stopped
Preliminary results indicated no measurable benefit.
Study Start Date
March 2009 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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?
Detailed Description
We set out to pursue the following Aims: Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity? Pilot studies were performed exploring the acute actions of salsalate on vascular function, the chronic actions of salasate in obese individuals, and actions of chronic salsalate to prevent vascular dysfunction induced by fatty acids in lean individuals. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin? No studies were performed Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril? No studies were performed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-diabetes, Obesity
Keywords
Vascular function, Glucose tolerance, Obesity, Pre-diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute Salsalate
Arm Type
Experimental
Arm Description
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.
Arm Title
Chronic Salsalate - Obese
Arm Type
Experimental
Arm Description
Obese subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months' treatment with oral salsalate.
Arm Title
Chronic Salsalate - Lean
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Chronic salsalate
Intervention Description
Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.
Intervention Type
Drug
Intervention Name(s)
Acute Salsalate
Intervention Description
Subjects will receive a single oral dose of 2 gram of oral salsalate
Primary Outcome Measure Information:
Title
Vascular Function
Description
The primary endpoints of interest is flow-mediated vasodilation
Time Frame
Measured at baseline and after a single oral dose of salsalate (Acute) or 2 months' treatment with salsalate (Chronic)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kieren J Mather, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana Clinical Research Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

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

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