Inflammation Inhibition in Prediabetic Humans — INCITE  

Prediabetes Clinical Trial

Official title: Inflammation Inhibition for Microvascular and Autonomic Dysfunction in Obese Prediabetic Humans

Status Terminated

Clinical Trial Summary

Prediabetes, characterized by elevated fasting blood sugar or exaggerated blood sugar response to sugar ingestion, effects over 79 million adult Americans and is a precursor to the development of Type 2 diabetes. Importantly, approximately 42% of Iowans (950,000) have diabetes and 32% (670,000) have prediabetes with the majority of those with prediabetes going undiagnosed. Adults with prediabetes demonstrate early signs of cardiovascular and nervous system abnormalities and are at high risk for developing overt diabetes unless aggressive lifestyle (weight loss, exercise) or pharmacological interventions are employed. Interestingly, data in recent years has linked obesity and diabetes to chronic inflammation of the blood vessels and brain areas that regulate blood pressure. Therefore, the current study will test whether a commonly used aspirin-like anti-inflammatory drug called salsalate, will improve blood vessel health and nervous system dysfunction in adults with prediabetes. Eligible subjects will have measurements of blood pressure, blood vessel function in the arms and eyes, assessments of nerve activity, and blood samples taken before and after 4 weeks of ingesting an FDA approved aspirin-like drug called salsalate. The study is important because it will identify a potentially new pharmacological strategy to treat vascular and nervous system abnormalities in overweight and obese adults with early stage type 2 diabetes using an inexpensive, generically available drug with an excellent safety record that has been used for decades to treat chronic inflammatory conditions such as rheumatoid arthritis. If proven effective, this will provide preliminary support for the concept of targeting inflammation as a new clinical approach to treating early diabetes related complications. Furthermore, the current pilot study will provide support for developing a larger clinical trial using salsalate that could potentially then be extended to patients with type 2 diabetes and cardiovascular disease, as well as lead to the development of new anti-inflammatory agents with greater specificity for selective inflammatory pathways.

Clinical Trial Description

A total of 30 healthy men and women ages 18-79 years who are obese defined as body mass index (BMI) of 30 kg/m2 or greater and with prediabetes (defined as fasting blood glucose between 100-126 mg/dl, a fasting blood glucose of 140-199 mg/dl at 120 min during an oral glucose tolerance test; or HbA1C of 6-6.5%) will be enrolled and randomized to 4-5 weeks of salsalate or placebo in the study. CONTROL GROUP: Another n=10 healthy obese men and women age 18-49 WITHOUT prediabetes will be enrolled for baseline testing but will not undergo randomization to the salsalate/placebo intervention. Therefore, total enrollment will be n=40.

All subjects will have no history of cardiovascular, metabolic or pulmonary disease as determined from medical history and physical exam, and a resting 12-lead ECG. Subjects may be on anti-hypertensive medications but will be asked to hold the medication on the morning of testing. Subjects on medications for Type I or II diabetes mellitus or for hyperlipidemia will be excluded (see complete list below). Subjects will be non-smokers or quit smoking at least one year ago. Women will have regular menses and will be tested during the early follicular phase of their menstrual cycle (within 8 days of onset of menses) to control for differences in circulating estradiol concentrations. Aim 1 will measure microvascular function and aortic wall stiffness in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 1 is that chronic inflammation inhibition will improve microvascular and large elastic artery function in obese adults with prediabetes. Aim 2 will measure muscle sympathetic nervous system activity (MSNA) and baroreflex sensitivity in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 2 is that chronic inflammation inhibition will decrease MSNA and improve baroreflex sensitivity in obese adults with prediabetes. ;

Related Conditions & MeSH terms

• Glucose Intolerance
• Inflammation
• Obese
• Prediabetes
• Prediabetic State

• NCT number: NCT01977417
• Study type: Interventional
• Source: University of Iowa
• Status: Terminated
• Phase: Phase 2
• Start date: November 2012
• Completion date: April 2021