Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 277
- 试验地点
- 16
- 主要终点
- Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1
研究概览
简要总结
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 first stage is a dose ranging study, administering salsalate compared to placebo over three months. 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.
The second stage is a second trial and posted under alternate registration.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Placebo
Placebo, appearance matched to active drug
干预措施: Placebo (Drug)
3 gram
Salsalate 3.0 grams daily, divided
干预措施: Salsalate (Drug)
3.5 gram
Salsalate 3.5 g daily, divided
干预措施: Salsalate (Drug)
4 gram
Salsalate 4.0 g daily, divided
干预措施: Salsalate (Drug)
结局指标
主要结局
Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1
时间窗: 14 week
The primary outcome for the TINSAL-T2D study is change in HbA1c level from baseline to week 14 (stage 1) in the intent-to-treat (ITT) population with last observation carried forward.
次要结局
- Change in HbA1c(14 week)
- Change From Baseline and Trends in Fasting Glucose Over Time(14 week)
- Change in Lipids(14 week)
- Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index(Baseline, week 14)
- Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index(Baseline, week 14)
- Safety and Tolerability(14 weeks)