Clinical trial NCT00258128: Effect of Salicylate on Glucose Metabolism in Insulin Resistance States
Official title: Effect of Salicylate on Glucose Metabolism in Insulin Resistance States
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Insulin Resistance
Lead sponsor: Joslin Diabetes Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2005-11-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Data supports diet induced obesity leads to activation of the IKK/NF-kB inflamatory pathway and that chronic inflammation leads to insulin resistance and diabetes. In rodents, salicylates inhibit IKK/NF-kB and may improve insulin sensitivity. We will study if this is true in people.

Detailed description: Please see the following review articles on this topic:

Shoelson SE, Lee J, Goldfine AB. (2006) Inflammation in insulin resistance. J. Clin. Invest. 116, 1793-1801.

Goldfine AB, Fonseca V and Shoelson SE (2010) Therapeutic approaches to target inflammation in type 2 diabetes. Clin Chem. 57, 162-167.

Donath MY and Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 11, 98-107.

Goldfine AB and Shoelson SE (2017) Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk. J Clin Invest. 127, 83-93.

Eligibility criteria: Inclusion Criteria:

age 18 to 65 years, inclusive; HbA1c \>6.0% (off medication-diabetic) normal hemoglobin and hematocrit, without donation of blood in the previous 2 months; without involvement in any study evaluating an investigational drug or device for the previous 2 months; normal clotting studies; female postmenopausal or surgically sterile, or using barrier or oral contraception and with a negative pregnancy test.

Exclusion Criteria:

pregnant or lactating women; patients with persistent ketonuria or a history of ketoacidosis (suggesting the need for insulin therapy); current of previous use of insulin for glucose control; patients with abnormal liver function defined as elevation of bilirubin, alkaline phosphatase, ALT, AST, or GGTP more than 1.5 times the upper limit of normal; patients with kidney disease (serum creatinine \> 1.5 mg/dL) macroalbuminuria (1+ protein on a standard urine dip-stick, or \> 300 mg urinary albumin/day)- (patients with microalbuminuria will be enrolled); patients with any significant diseases or conditions, including emotional or psychiatric disorders and substance abuse, including history of binge drinking, that, in the opinion of the investigator, are likely to alter the patient's ability to complete the study; patients with metabolic acidosis (abnormal anion gap); history of gastric ulcer, dyspepsia, or upper or lower GI bleed; history of allergy to aspirin, or bleeding diathesis or currently on oral anticoagulants including warfarin, heparin, aspirin or other NSAIDs; patients with major vascular event within 6 months of screening for the study (e.g., myocardial infarction stroke, coronary artery bypass graft (CABG) surgery, angioplasty, peripheral vascular surgery); patients with chronic heart disease, or a history of myocardial infarction or stroke. Symptomatic angina pectoris or cardiac insufficiency as defined by the NYHA; classification as Functional Class III or IV; patients with HbA1C \> 13% (normal range 4-6%); patients who smoke more than one pack of cigarettes daily; patients taking treatment medications known to affect insulin sensitivity (e.g. diuretics, beta-blockers); patients taking warfarin, heparin or NSAID on a chronic basis; patients with inadequately controlled serum lipid levels (total cholesterol ≥ 275 mg/dL and fasting triglycerides ≥ 450 mg/dL); patients with history of cancer within 5 years prior to screening for the study other than basal cell carcinoma; active alcohol or other substance abuse.

Primary outcomes:
measure: Glucose
timeFrame: 4 weeks
Secondary outcomes:
measure: Adiponectin
timeFrame: 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Joslin Diabetes Center
name: Steven Shoelson
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fleischman 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.
citation: Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.
citation: Goldfine 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.