Using Salsalate to Target Adipocyte Macrophage Infiltration (TAMI)

May 1, 2014 updated by: Michael I. Goran, University of Southern California

Using Salsalate to Target Adipocyte Macrophage Infiltration and Reverse Metabolic Disease Risk in Obese Hispanic Young Adults

Background: The prevalence of obesity has increased throughout the last three decades due to genetic, metabolic, behavioral, and environmental factors. Obesity and high-fat western diets activate inflammatory processes, which promote development of insulin resistance as well as other metabolic complications. Increasing obesity rates are a major public health concern in the Hispanic population due to the large number of Hispanics suffering from obesity. Based on preliminary data, we propose a double-blind randomized clinical trial of Salsalate therapy in obese Hispanic young adults. Salsalate treatment shows promise for decreasing inflammation under conditions of weight stability by reducing macrophage infiltration of adipocytes. Hispanics have the greatest amount of visceral adipose tissue (VAT), liver fat, and inflammation when compared to other ethnic groups, thereby increasing the potential for treatment effects in this high-risk population.

Purpose: The purpose of this study is to demonstrate through a "proof-of-concept" trial that Salsalate induced reductions in adipose tissue inflammation are possible under conditions of weight stability.

Methodology: We will recruit obese Hispanic young adults (18 - 35 years) from hospitals, clinics, and community centers. Study Endpoints: Primary outcomes will be macrophage infiltration as assessed by the presence of crown-like structures (CLS) in subcutaneous adipose tissue (SAT) biopsies, liver fat, insulin sensitivity, and fasting glucose. We will also assess plasma levels of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1, C-reactive protein (CRP), and SAT gene expression of nuclear factor kB (NF-kB) and insulin signaling pathways.

Intervention and Follow-up: Participants will be randomly assigned to four weeks of treatment with Salsalate (4 g/d) or placebo and will be studied under weight maintenance conditions. These measures will enable us to determine if Salsalate treatment is capable of reducing adipose tissue inflammation and related metabolic outcomes in the absence of weight loss.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

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
    • California
      • Los Angeles, California, United States, 90089
        • University of Southern California Diabetes Obesity Research Institute (DORI)
      • Los Angeles, California, United States, 90089
        • University of Southern California, Clinical Trials Unit (CTU)

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 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Obese (body mass index >30 kg/m^2)
  • Hispanic males and females age 18-35 years

Exclusion Criteria:

  • Women with hemoglobin <11.5 g/dL or men with hemoglobin <12.5 g/dL will be excluded
  • AST / ALT >2 times the upper limit of normal
  • Evidence of any liver disease other than non-alcoholic steatosis
  • Diabetes
  • Diagnosis of any disease that is known to influence insulin action and secretion
  • Current or past involvement in any weight loss, exercise, or sports program in the six months prior to participation
  • Use of medication known to influence body composition or fat distribution (e.g. Cushing syndrome)
  • History of renal disease
  • Use of non-steroidal anti-inflammatory drugs (NSAIDs)
  • Chicken pox, flu, or influenza infection
  • Those taking high doses of vitamin C, antacids (containing Ca2+ or Mg+2), or taking Warfarin
  • Hypertension
  • Allergies to Salsalate, aspirin or other NSAIDs
  • History of peptic ulcer or upper GI bleeding
  • A positive pregnancy test or current lactation
  • Has smoked greater than 100 cigarettes in their lifetime and now smokes everyday or some days
  • Drinks greater than 200 g/day of alcohol
  • Those with a waist circumference (or widest part of body measurement) greater than or equal to 185 cm due to MRI size restrictions

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Salsalate
Salsalate (4 g/day)
Drug: Salsalate (4 g/day)
Given orally twice daily
Other Names:
  • Salicylate
Placebo Comparator: Placebo
Placebo (4 g/day)
Drug: Placebo (4 g/day)
Given orally twice daily
Other Names:
  • Inactive control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma glucose levels over a 2-hour oral glucose tolerance test
Time Frame: 4 weeks
Glucose following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma glucose levels.
4 weeks
Change in adipose tissue inflammation
Time Frame: 4 weeks
Adipose tissue inflammation following 4 weeks of treatment with salsalate (4 g/day) or placebo. Adipose tissue inflammation will be determined from abdominal subcutaneous adipose tissue biopsies performed at baseline and 4 weeks.
4 weeks
Change in systemic markers of inflammation
Time Frame: 4 weeks
Systemic markers of inflammation following treatment with salsalate (4 g/day) or placebo. Fasting blood samples will be taken at baseline and 4 weeks to measure systemic markers of inflammation.
4 weeks
Change in plasma insulin levels over a 2-hour oral glucose tolerance test
Time Frame: 4 weeks
Insulin following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma insulin levels.
4 weeks
Change in plasma fasting free fatty acid levels
Time Frame: 4 weeks
Fasting free fatty acids (FFA) following 4 weeks of treatment with salsalate (4 g/day) or placebo. Fasting blood samples will be taken at baseline and 4 weeks to measure changes in plasma fasting FFA.
4 weeks
Change in plasma C-peptide levels over a 2-hour oral glucose tolerance test
Time Frame: 4 weeks
C-peptide following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 2-hour oral glucose tolerance test will be performed at baseline and 4 weeks to measure changes in plasma C-peptide levels.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body composition
Time Frame: 4 weeks
Changes in body composition following 4 weeks of treatment with salsalate (4 g/day) or placebo. A DEXA scan will be performed at baseline and 4 weeks to measure any potential changes in body composition (body fat and lean tissue mass).
4 weeks
Change in ectopic fat
Time Frame: 4 weeks
Changes in ectopic fat following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 3-Tesla whole abdominal MRI scan will be performed at baseline and 4 weeks to measure any potential changes in ectopic fat.
4 weeks
Change in diet
Time Frame: 4 weeks
Changes in diet following 4 weeks of treatment with salsalate (4 g/day) or placebo. A 24-hour diet recall will be performed at baseline and 4 weeks to measure any potential changes in diet.
4 weeks
Change in physical activity
Time Frame: 4 weeks
Changes in physical activity following 4 weeks of treatment with salsalate (4 g/day) or placebo. A Godin-Shephard Leisure-Time Physical Activity questionnaire will be performed at baseline and 4 weeks to measure any potential changes in physical activity.
4 weeks

Collaborators and Investigators

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

Sponsor

University of Southern California

Investigators

  • Principal Investigator: Tanya L Alderete, University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2011

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

April 29, 2014

First Submitted That Met QC Criteria

May 1, 2014

First Posted (Estimate)

May 5, 2014

Study Record Updates

Last Update Posted (Estimate)

May 5, 2014

Last Update Submitted That Met QC Criteria

May 1, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-11-00017

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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