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NCT Number: NCT02130804

Using Salsalate to Target Adipocyte Macrophage Infiltration

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.

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Key information

Conditions

Diabetes Risk Body Weight Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Southern California Diabetes Obesity Research Institute (DORI), Los Angeles, California, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Salsalate (4 g/day)

Drug

Given orally twice daily

Other names: Salicylate

Placebo (4 g/day)

Drug

Given orally twice daily

Other names: Inactive control

Primary outcomes

  1. 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.

  2. 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.

  3. 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. 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.

  5. 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.

  6. 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.

Secondary outcomes

  1. 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).

  2. 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.

  3. 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. 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.

Sponsors and collaborators

Lead sponsor

University of Southern California

Other

Registry information

Official study title

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

Acronym: TAMI

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
May 5, 2014
Registry last updated
May 5, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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