October 25, 2006 |
November 26, 2008 |
October 2006 |
The primary outcome for the TINSAL-T2D study is change in HbA1c level from baseline to week 14 (stage 1) or 26 (stage 2) in the intent-to-treat (ITT)
population with last observation carried forward. [ Time Frame: 14-26 week ] |
Same as current |
Complete list of historical versions of study NCT00392678 on ClinicalTrials.gov Archive Site |
- Change from baseline to either 14 or 26 weeks, or last HbA1c measurement prior to rescue therapy [ Time Frame: 14-26 week ]
- Change from baseline and trends in fasting glucose over time [ Time Frame: 14-26 week ]
- Response rates for reduction in fasting glucose of ≥20 mg/dl, a reduction in HbA1c of ≥0.5%, and a reduction in HbA1c of ≥0.8% [ Time Frame: 14-26 week ]
- Change in lipids (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], triglycerides [TG], total
cholesterol [TC], high-density lipoprotein cholesterol [HDL C], TC/HDL-C ratio, and LDL-C/HDL-C ratio) [ Time Frame: 14-26 week ]
- Change in insulin sensitivity (insulin, C-peptide, homeostasis model [HOMA] index) [ Time Frame: 14-26 week ]
- Response rates for exceeding hyperglycemic targets between active and placebo treated groups [ Time Frame: 14-26 week ]
- Need for rescue therapy [ Time Frame: 14-26 week ]
- Need for discontinuation of study medication [ Time Frame: 14-26 week ]
- Response rates in patients initially treated with lifestyle modification, insulin secretagogue, metformin or combination therapy [ Time Frame: 14-26 week ]
- Response rates for a reduction in HbA1c for obese vs non-obese participants [ Time Frame: 14-26 week ]
- Safety and tolerability of salsalate compared to placebo [ Time Frame: 14-26 weeks ]
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- Change from baseline to either 26 weeks or last HbA1c measurement prior to rescue therapy
- Trends in HbA1c over time
- Change from baseline and trends in fasting glucose over time
- Response rates for reduction in fasting glucose of ≥20 mg/dl, a reduction in HbA1c of ≥0.5%, and a reduction in HbA1c of ≥0.8%
- Change in lipids (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], triglycerides [TG], total
cholesterol [TC], high-density lipoprotein cholesterol [HDL C], TC/HDL-C ratio, and LDL-C/HDL-C ratio)
- Change in insulin sensitivity (insulin, C-peptide, homeostasis model [HOMA] index)
- Response rates for exceeding hyperglycemic targets between active and placebo treated groups
- Need for rescue therapy
- Need for discontinuation of study medication
- Response rates in patients initially treated with lifestyle modification, insulin secretagogue, metformin or combination therapy
- Response rates for a reduction in HbA1c for obese vs non-obese participants
- Safety and tolerability of salsalate compared to placebo
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Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D) |
Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate |
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 determine whether salsalate, a member of the commonly used Non-Steroidal Anti-Inflammatory Drug (NSAID) class, is effective in lowering sugars in patients with type 2 diabetes. The study will determine whether salicylates represent a new pharmacological option for diabetes management. The study is conducted in two stages. The primary objective of the first stage is to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. The primary objective of Stage 2 of the study is to evaluate the effects of salsalate on blood sugar control in diabetes; the tolerability of salsalate use in patients with type 2 diabetes (T2D); and the effects of salsalate on measures of inflammation, the metabolic syndrome, and cardiac risk. |
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Phase II, Phase III |
Interventional |
Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Type 2 Diabetes |
Drug: Salsalate |
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Active, not recruiting |
402 |
December 2010 |
July 2008 (final data collection date for primary outcome measure) |
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
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Both |
18 Years to 75 Years |
No |
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United States |
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NCT00392678 |
Allison Goldfine, MD, Joslin Diabetes Center, Boston, MA |
U01 DK074556 |
Joslin Diabetes Center |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
Principal Investigator: |
Steven E. Sheolson, MD, PhD |
Joslin Diabetes Center |
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Study Director: |
Allison B. Goldfine, MD |
Joslin Diabetes Center |
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Study Director: |
Vivian Fonseca, MD |
Tulane University School of Medicine |
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Study Director: |
Kathleen Jablonski, PhD |
George Washington University |
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Study Director: |
Myrlene Staten, MD |
National Institute of Diabetes & Digestive & Kidney Diseases |
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Joslin Diabetes Center |
November 2008 |