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Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II (TINSALT2D-II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00799643
Recruitment Status : Completed
First Posted : December 1, 2008
Results First Posted : November 25, 2013
Last Update Posted : December 11, 2017
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Joslin Diabetes Center

Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Salsalate Drug: Salsalate Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 638 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate
Study Start Date : November 2008
Actual Primary Completion Date : September 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
Salsalate, 3.5 g/d orally, divided dosing
Drug: Salsalate
Salsalate 3.5 g/d orally, divided dosing
Other Name: disalsid

Placebo Comparator: 2
Salsalate Placebo, orally, divided dosing
Drug: Salsalate Placebo

Primary Outcome Measures :
  1. The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups. [ Time Frame: 48 weeks from baseline ]
    HbA1c (%, percentage of HbA1c) change from baseline.

Secondary Outcome Measures :
  1. Change From Baseline in Fasting Glucose Over Time. [ Time Frame: 48 weeks from baseline ]
  2. 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: 24 and 48 weeks ]
  3. 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: 48 weeks ]
  4. Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers [ Time Frame: 24 and 48 weeks ]
  5. Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication [ Time Frame: 24 and 48 weeks ]
  6. Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy [ Time Frame: 24 and 48 weeks ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. FPG ≤ 225 mg/dL and HbA1c≥7% and ≤ 9.5% at screening.
  3. Age ≥18 and <75
  4. Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm)

Exclusion Criteria:

  1. No prior participation in Stage I of TINSAL-T2D ; exception: a participant who failed screening for HbA1c in Stage I will be allowed to re-screen for Stage II.
  2. Type 1 diabetes and/or history of ketoacidosis determined by medical history
  3. History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation
  4. History of long-term therapy with insulin (>30 days) within the last year
  5. 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
  6. Pregnancy or lactation
  7. Patients requiring oral corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks)
  8. 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
  9. Surgery within 30 days prior to screening
  10. 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
  11. History of chronic liver disease including hepatitis B or C
  12. History of peptic ulcer or endoscopy demonstrated gastritis
  13. History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
  14. 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
  15. New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure
  16. History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months
  17. 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). If on blood pressure medications, dosing should be stable for 2 weeks prior to randomization.
  18. 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)
  19. Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening*
  20. Platelets <100,000 cu mm at screening
  21. AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening
  22. Total Bilirubin >1.50 x ULN at screening
  23. Triglycerides (TG) >500 mg/dL at screening
  24. Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study
  25. Previous allergy to aspirin
  26. Chronic or continuous use (daily for more than 7 days) of nonsteroidal anti-inflammatory drugs within the preceding 2 months
  27. Use of warfarin (Coumadin), clopidogrel (Plavix), dipyridamole (Persantine), heparin or other anticoagulants
  28. Use of probenecid (Benemid, probalan), sulfinpyrazone (Anturane) or other uricosuric agents
  29. Macroalbuminuria, defined as spot urine protein >300 mcg/mg Cr at screening
  30. Pre-existing chronic tinnitus

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00799643

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Sponsors and Collaborators
Joslin Diabetes Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Steven E. Shoelson, MD, PhD Joslin Diabetes Center
Study Director: Allison B. Goldfine, MD Joslin Diabetes Center
Study Director: Vivian Fonseca, MD Tulane University
Study Director: Kathleen Jablonski, PhD George Washington University
Study Director: Myrlene Staten, MD National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Joslin Diabetes Center Identifier: NCT00799643    
Other Study ID Numbers: CHS 06-20-2
U01DK074556 ( U.S. NIH Grant/Contract )
First Posted: December 1, 2008    Key Record Dates
Results First Posted: November 25, 2013
Last Update Posted: December 11, 2017
Last Verified: November 2017
Keywords provided by Joslin Diabetes Center:
Type 2 Diabetes Mellitus (T2D)
Metabolic Syndrome
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Salicylsalicylic acid
Sodium Salicylate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action