Phase 3
Completed N=286
Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II
Source: ClinicalTrials.gov NCT00799643 ↗Enrolled (actual)
286
Serious AEs
5.6%
Results posted
Nov 2013
Primary outcomePrimary: The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups. — -0.04; -0.33 HbA1c units are %
Summary
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. Enrollment in the first stage is complete. The primary objective of the first stage was 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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups. |
-0.04; -0.33 | — |
| SECONDARY Change From Baseline in Fasting Glucose Over Time. |
2.0; -13.1 | — |
| SECONDARY 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% |
— | — |
| SECONDARY 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) |
— | — |
| SECONDARY Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers |
— | — |
| SECONDARY Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication |
— | — |
| SECONDARY Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy |
— | — |
Eligibility Criteria
Inclusion Criteria
- Type 2 diabetes on diet and exercise therapy or monotherapy with metformin, insulin secretagogue (including SFU, non-SFU, and dipeptidyl peptidase IV (DPP-4) inhibitors), alpha-glucosidase inhibitors, or bile acid sequestrants (dosed once per day such that study drug can be administered ≥ 4 hours prior to sequestrant); or a combination of up to two of these at maximal dose. Dosing must be stable for 8 weeks prior to screening. Participant must have been diagnosed with T2D at least 8 weeks before screening.
- FPG ≤ 225 mg/dL and HbA1c≥7% and ≤ 9.5% at screening.
- Age ≥18 and 30 days) within the last year
- Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), alone or in combination in the previous 6 months; or exendin-4 (Byetta), alone or in combination in the previous 3 months
- Pregnancy or lactation
- Patients requiring oral 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 150 mmHg or diastolic blood pressure >95 mmHg on three or more assessments on more than one day). If on blood pressure medications, dosing should be stable for 2 weeks prior to randomization.
- History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed DCCktail containing 1 ounce of alcohol)
- Hemoglobin 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), dipyridamole (Persantine), heparin or other anticoagulants
- Use of probenecid (Benemid, probalan), sulfinpyrazone (Anturane) or other uricosuric agents
- Macroalbuminuria, defined as spot urine protein >300 mcg/mg Cr at screening
- Pre-existing chronic tinnitus
Data sourced from ClinicalTrials.gov (NCT00799643). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.