Diabetes RiskPhase 1TAMINCT02130804
Using Salsalate to Target Adipocyte Macrophage Infiltration
A Phase 1 study testing Salsalate (4 g/day) in people with Diabetes Risk, run by University of Southern California at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Risk
- What is being tested?
- Salsalate (4 g/day)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2011to Oct 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Obese (body mass index >30 kg/m^2)
- Hispanic males and females age 18-35 years
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Southern California Diabetes Obesity Research Institute (DORI)
Los Angeles, California, 90089
University of Southern California, Clinical Trials Unit (CTU)
Los Angeles, California, 90089
About this study
Official title: 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.
Read more
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.
- Conditions
- Diabetes Risk
- Being tested
- Salsalate (4 g/day), Placebo (4 g/day)
- Keywords
- Obesity, Adipose tissue inflammation, Salsalate, Hispanics
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salsalate (4 g/day)Drug
Also called Salicylate
Given orally twice daily
Placebo (4 g/day)Drug
Also called Inactive control
Given orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| Salsalate | Experimental | Salsalate (4 g/day) Receives: Drug: Salsalate (4 g/day) |
| Placebo | Placebo comparator | Placebo (4 g/day) Receives: Drug: Placebo (4 g/day) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma glucose levels over a 2-hour oral glucose tolerance test
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.
Measured: 4 weeks
Change in adipose tissue inflammation
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.
Measured: 4 weeks
Change in systemic markers of inflammation
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.
Measured: 4 weeks
Change in plasma insulin levels over a 2-hour oral glucose tolerance test
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.
Measured: 4 weeks
Change in plasma fasting free fatty acid levels
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.
Measured: 4 weeks
Change in plasma C-peptide levels over a 2-hour oral glucose tolerance test
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.
Measured: 4 weeks
Secondary outcomes (4)
Change in body composition
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).
Measured: 4 weeks
Change in ectopic fat
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.
Measured: 4 weeks
Change in diet
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.
Measured: 4 weeks
Change in physical activity
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2014 (estimated)
- Study startJul 2011
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetes RiskStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael I. Goran, University of Southern California
- Investigators
- Michael I Goran, PhD, Principal investigator, University of Southern CaliforniaTanya L Alderete, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02130804
- Sponsor's protocol ID
- HS-11-00017
- Acronym
- TAMI
- Status last verified
- May 2014
- First submitted
- 29 Apr 2014
- Last updated
- 5 May 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Goldfine AB, Conlin PR, Halperin F, Koska J, Permana P, Schwenke D, Shoelson SE, Reaven PD. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia. 2013 Apr;56(4):714-23. doi: 10.1007/s00125-012-2819-3. Epub 2013 Jan 31.
PubMed 23370525Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE; TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2010 Mar 16;152(6):346-57. doi: 10.7326/0003-4819-152-6-201003160-00004.
PubMed 20231565Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008 May;1(1):36-43. doi: 10.1111/j.1752-8062.2008.00026.x.
PubMed 19337387Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008 Feb;31(2):289-94. doi: 10.2337/dc07-1338. Epub 2007 Oct 24.
PubMed 17959861Koska J, Ortega E, Bunt JC, Gasser A, Impson J, Hanson RL, Forbes J, de Courten B, Krakoff J. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia. 2009 Mar;52(3):385-93. doi: 10.1007/s00125-008-1239-x. Epub 2008 Dec 23.
PubMed 19104769Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Reduction of insulin resistance and plasma glucose level by salsalate treatment in persons with prediabetes. Endocr Pract. 2012 Nov-Dec;18(6):826-33. doi: 10.4158/EP12064.OR.
PubMed 22784842Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes. Acta Diabetol. 2013 Aug;50(4):537-43. doi: 10.1007/s00592-011-0329-2. Epub 2011 Sep 22.
PubMed 21938543
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Salsalate to Target Adipocyte Macrophage Infiltration and Reverse Metabolic Disease Risk in Obese Hispanic Young Adults
- ClinicalTrials.gov ID
- NCT02130804
- Acronym / sponsor ID
- TAMI / HS-11-00017
- Conditions
- Diabetes Risk
- Keywords
- Obesity, Adipose tissue inflammation, Salsalate, Hispanics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 5 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Salsalate | Experimental | Drug: Salsalate (4 g/day)Salsalate (4 g/day) |
| Placebo | Placebo comparator | Drug: Placebo (4 g/day)Placebo (4 g/day) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Obese (body mass index >30 kg/m^2)
- Hispanic males and females age 18-35 years
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Salsalate (4 g/day)Also: SalicylateGiven orally twice daily | Drug | Salsalate |
| Placebo (4 g/day)Also: Inactive controlGiven orally twice daily | Drug | Placebo |
Primary outcome
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.
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.
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.
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.
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.
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 secondary outcomes
Change in body composition
Time frame: 4 weeks
Change in ectopic fat
Time frame: 4 weeks
Change in diet
Time frame: 4 weeks
Change in physical activity
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2014.
- Background: PubMed 23370525Goldfine AB, Conlin PR, Halperin F, Koska J, Permana P, Schwenke D, Shoelson SE, Reaven PD. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia. 2013 Apr;56(4):714-23. doi: 10.1007/s00125-012-2819-3. Epub 2013 Jan 31.
- Background: PubMed 20231565Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE; TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2010 Mar 16;152(6):346-57. doi: 10.7326/0003-4819-152-6-201003160-00004.
- Background: PubMed 19337387Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008 May;1(1):36-43. doi: 10.1111/j.1752-8062.2008.00026.x.
- Background: PubMed 17959861Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008 Feb;31(2):289-94. doi: 10.2337/dc07-1338. Epub 2007 Oct 24.
- Background: PubMed 19104769Koska J, Ortega E, Bunt JC, Gasser A, Impson J, Hanson RL, Forbes J, de Courten B, Krakoff J. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia. 2009 Mar;52(3):385-93. doi: 10.1007/s00125-008-1239-x. Epub 2008 Dec 23.
- Background: PubMed 22784842Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Reduction of insulin resistance and plasma glucose level by salsalate treatment in persons with prediabetes. Endocr Pract. 2012 Nov-Dec;18(6):826-33. doi: 10.4158/EP12064.OR.
- Background: PubMed 21938543Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes. Acta Diabetol. 2013 Aug;50(4):537-43. doi: 10.1007/s00592-011-0329-2. Epub 2011 Sep 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael I Goran, PhD principal investigator
University of Southern California
Tanya L Alderete principal investigator
University of Southern California
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Salsalate (4 g/day) in people with Diabetes Risk, run by University of Southern California at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma glucose levels over a 2-hour oral glucose tolerance test (time frame: 4 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02130804, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2014.