Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk

2014-08-27 03:44:26 | BioPortfolio


The hypothesis is that salsalate therapy may be an effective and safe method to modulate inflammation in metabolically-critical tissues and thus reduce insulin resistance and its related complications.

The objectives of the study are to (1) determine whether salsalate therapy improves insulin resistance in subjects with IGT and changes in glucose area under the curve following a standard oral glucose tolerance test (OGTT); (2) determine whether salsalate therapy reduces a) plasma levels of a variety of well established inflammatory proteins and b) mononuclear cell inflammatory activity to provide evidence of reduced systemic and tissue inflammation, respectively; and (3)also determine whether salsalate therapy improves parameters of cardiovascular disease risk, including features of metabolic syndrome (fasting glucose, triglycerides, HDL, and blood pressure) as well as endothelial dysfunction.


Recent studies demonstrate an important role for sub-acute, chronic inflammation in the development of insulin resistance, type 2 diabetes mellitus (T2 DM) and cardiovascular disease (CVD). A broad body of data indicate that obesity and high fat or "Western" diets activate sub-acute inflammatory processes in fat and liver tissue as well as in mononuclear cells. The inflammatory mediators produced by these tissues and cells promote the development of insulin resistance both locally and at distant sites such as skeletal muscle. These same inflammatory mediators may also increase the risk for CVD. Work from our labs indicate that Nuclear Factor-kappa B (NF-kB), an inflammatory master switch for a multitude of proinflammatory genes and pathways, is activated in fat and liver by obesity and high fat diets. We have also noted similar NF-kB activation in monocytes and macrophages in similar conditions of nutritional excess. It has become evident that salicylates inhibit the NF-kB regulatory protein IKKB and we have subsequently demonstrated their ability to downregulate NF-kB activation in each of these above tissues in animals. Moreover,by inhibiting the IKKB/NF-kB pathway, salicylates appear to ameliorate insulin resistance and its associated metabolic abnormalities and potentially provide a new approach for pharmacologic treatment of T2 DM as well as individuals with conditions such as impaired glucose intolerance (IGT) to prevent their progression to diabetes. Preliminary results from a two-week trail is T2 DM patients indicated that high-dose aspirin(ASA,~7g/day) improved glucose metabolism and associated risk factors. While this was as important first step towards proof-of-principle, the risk of severe gastrointestinal bleeding associated with high-dose ASA precludes broader use. Salicylate in its prodrug form of salsalate(Disalcid), is much safer than ASA(as it does not irritate the gastric mucosa nor alter bleeding times). We have now conducted several preliminary short-term in individuals with IGT or T2 DM as well in obese insulin resistant subjects and have demonstrated that salsalate in doses of 3.5-4.5g/d provides similar blood salicylate levels as high dose ASA and induces similar clinical and metabolic benefits over the 2-4 weeks study duration. Therefore, in vitro, animal and human clinical studies all support the concept that inhibiting the IKKB/NF-kB pathway with salsalates is a feasable approach to reducing insulin resistance. This study will more fully characterize the metabolic benefits of high dose salsalate therapy.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention




Salsalate, Placebo


Carl T. Hayden VA Medical Center
United States


Active, not recruiting


Department of Veterans Affairs

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:44:26-0400

Clinical Trials [316 Associated Clinical Trials listed on BioPortfolio]

Inflammation and Vascular Function in Atherosclerosis

The purpose of this study is to determine whether reducing inflammation in blood vessels with an aspirin-like drug called salsalate will improve blood vessel function.

Targeting Inflammation Using Salsalate in CardioVascular Disease

The hypothesis is that western lifestyle, with sedentary behaviors and caloric excess promote a chronic, subacute inflammatory state that participates in the development and progression of...

Salsalate in Patients Mild to Moderate Alzheimer's Disease

The purpose of the study is to test the safety and tolerability of twice daily Salsalate in patients with mild to moderate Alzheimer's Disease. Half of the participants will receive Salsal...

Targeting Inflammation Using Salsalate for Type 2 Diabetes-stage II

Growing evidence over recent years supports a potential role for low grade chronic inflammation in the pathogenesis of insulin resistance and type 2 diabetes. In this study we will determi...

The Comparison of Effect Between Salsalate and Placebo in Osteoarthritis With Nonalcoholic Fatty Liver Disease

This Study purpose to verify change of variety factors that the cause of nonalcoholic fatty liver disease and its process through salsalate injection to osteoarthritis patient who has non ...

PubMed Articles [1671 Associated PubMed Articles listed on BioPortfolio]

Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification.

Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. Among them, we reported that MMP10 is present in human atheroma, associated with atherosclerosis. H...

Progranulin in the hematopoietic compartment protects mice from atherosclerosis.

Progranulin is a circulating protein that modulates inflammation and is found in atherosclerotic lesions. Here we determined whether inflammatory cell-derived progranulin impacts atherosclerosis devel...

Using Placebo Beverages in Group Alcohol Studies.

Placebo beverage conditions remain a key element in the methodological toolkit for alcohol researchers interested in evaluating pharmacological and nonpharmacological factors influencing the effects o...

Disruption of a CD1d-mediated interaction between mast cells and NKT cells aggravates atherosclerosis.

The development of atherosclerosis is tightly regulated by the innate and adaptive immune system. Communication between these two compartments occurs, among others, upon presentation of lipid antigens...

A short essay on the spirituality of placebo from an (evolutionary) psychiatric perspective.

Different to spirituality, the placebo-effect is well operationalized. Against this background, an attempt is made to look at a possible phenomenological relationship between the therapeutic effective...

Medical and Biotech [MESH] Definitions

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.

Lack of perfusion in the EXTREMITIES resulting from atherosclerosis. It is characterized by INTERMITTENT CLAUDICATION, and an ANKLE BRACHIAL INDEX of 0.9 or less.

Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.

A drug that has been given by mouth in the treatment of atherosclerosis and other vascular disorders, hyperlipidemias, and thrombo-embolic disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1408)

More From BioPortfolio on "Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk"

Quick Search


Relevant Topic

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Searches Linking to this Trial