Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D)

The primary objective of the first stage of the TINSAL-T2D trial is to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. The trial is a multicenter, single mask lead-in, double masked placebo controlled dose ranging study, comparing salsalte to placebo over 3 months.

Inclusion criteria

• Type 2 diabetes on diet and exercise therapy or monotherapy with metformin, insulin secretagogue, or alpha-glucosidase inhibitors, or a low-dose combination of these at ≤ 50% maximal dose (see Appendix). Dosing is stable for 8 weeks prior to randomization.
• FPG ≤ 225 mg/dL and HbA1c>7% and ≤9.5% at screening
• Age ≥18 and <75
• Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm)

Exclusion criteria

• Type 1 diabetes and/or history of ketoacidosis determined by medical history
• History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation
• History of long-term therapy with insulin (>30 days) within the last year
• Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4 (Byetta), alone or in combination in the previous 6 months
• Pregnancy or lactation
• Patients requiring corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks)
• Use of weight loss drugs [e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications] within 3 months of screening or intentional weight loss of ≥ 10 lbs in the previous 6 months
• Surgery within 30 days prior to screening
• Serum creatinine >1.4 for women and >1.5 for men or eGFR <60 [possible chronic kidney disease stage 3 or greater calculated using the Modification of Diet in Renal Disease (MDRD) equation.
• History of chronic liver disease including hepatitis B or C
• History of peptic ulcer or endoscopy demonstrated gastritis
• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
• History of malignancy, except participants who have been disease-free for greater than 10 years, or whose only malignancy has been basal or squamous cell skin carcinoma
• New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months
• Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg on three or more assessments on more than one day)
• History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)
• Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening
• Platelets <100,000 cu mm at screening.
• AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening
• Total Bilirubin >1.50 x ULN at screening
• Triglycerides (TG) >500 mg/dL at screening
• Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study
• Previous allergy to aspirin
• Chronic or continuous use (daily for more than 7 days) of nonsteroidal anti-inflammatory drugs within the preceding 2 months
• Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants
• Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents