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

June 5, 2019 updated by: Indiana University

Aims:

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

We set out to pursue the following Aims:

  1. 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.
  2. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin? No studies were performed
  3. 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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acute Salsalate
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
Subjects will receive a single oral dose of 2 gram of oral salsalate
Experimental: Chronic Salsalate - Obese
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
Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.
Experimental: Chronic Salsalate - Lean
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
Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vascular Function
Time Frame: Measured at baseline and after a single oral dose of salsalate (Acute) or 2 months' treatment with salsalate (Chronic)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Investigators

  • Principal Investigator: Kieren J Mather, MD, Indiana University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

February 4, 2009

First Submitted That Met QC Criteria

February 4, 2009

First Posted (Estimate)

February 5, 2009

Study Record Updates

Last Update Posted (Actual)

August 1, 2019

Last Update Submitted That Met QC Criteria

June 5, 2019

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IU-IRB-0901-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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