Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00330733
Status:
COMPLETED
Last Update Posted:
2020-01-21
First Post:
2006-05-26
Brief Title:
Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk
Status:
COMPLETED
Status Verified Date:
2020-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 3also 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
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 3also 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
Detailed Description:
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 inhibitor of Kappa B Kinase and we have subsequently demonstrated their ability to downregulate NF-kB activation in each of these above tissues in animals Moreover by inhibiting the IKKBNF-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 aspirinASA7gday 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 salsalateDisalcid is much safer than ASAas 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 35-45gd 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 IKKBNF-kB pathway with salsalate is a feasible approach to reducing insulin resistance This study will more fully characterize the metabolic benefits of high dose salsalate therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None