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Targeting Inflammation Using Salsalate for Type 2 Diabetes-stage II (TINSAL-T2D-II)
This study is currently recruiting participants.
Verified by Joslin Diabetes Center, September 2009
First Received: November 26, 2008   Last Updated: September 18, 2009   History of Changes
Sponsor: Joslin Diabetes Center
Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00799643
  Purpose

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 Intervention Phase
Type 2 Diabetes Mellitus
Drug: Salsalate
Drug: Salsalate Placebo
Phase II
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate

Resource links provided by NLM:


Further study details as provided by Joslin Diabetes Center:

Primary Outcome Measures:
  • The primary outcome for the TINSAL-T2D study is change in HbA1c level from baseline to week 48, compared between treatment groups. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Change in insulin sensitivity [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Changes in WBC and differential, high-sensitivity C reactive protein (hsCRP), other inflammatory markers [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline and trends in fasting glucose over time. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Response rates in patients initially treated with lifestyle modification, insulin secretagogue, metformin or combination therapy [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 564
Study Start Date: November 2008
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
Salsalate, 3.5 g/d orally, divided dosing
Drug: Salsalate
Salsalate 3.5 g/d orally, divided dosing
2: Placebo Comparator
Salsalate Placebo, orally, divided dosing
Drug: Salsalate Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, gastroporesis 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 extendin-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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00799643

Contacts
Contact: Allison B. Goldfine, MD 617-732-2643 allison.goldfine@joslin.harvard.edu
Contact: Elizabeth Tatro 617-732-2400 ext 4463 elizabeth.tatro@joslin.harvard.edu

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States
Contact: Tiffany Grimes     205-934-4112     tdgrimes@uab.edu    
Principal Investigator: Fernando Ovalle, MD            
United States, California
University of California, San Diego Recruiting
San Diego, California, United States
Contact: Jacqueline Raceles     858-552-8585 ext 4384     Jacqueline.Raceles@va.gov    
Principal Investigator: Robert Henry, MD            
United States, Connecticut
Chapel Medical Group Recruiting
New Haven, Connecticut, United States
Contact: Jennifer Flynn     203-865-5111     jjstrat16@yahoo.com    
Principal Investigator: Wayne Warren, MD            
United States, District of Columbia
Medstar Research Institute Recruiting
Washington, District of Columbia, United States
Contact: Adeola Akindana     202-787-5313     adeola.akindana@medstar.net    
Principal Investigator: Vanita Aroda, MD            
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States
Contact: Gonzalo Robalino     404-616-3719     garobal@emory.edu    
Principal Investigator: Guillermo Umpierrez, MD            
Kaiser Permanente Recruiting
Tucker, Georgia, United States
Contact: Michelle Stevens     770-496-3421     Michelle.D.Stevens@kp.org    
Principal Investigator: Joshua Barzilay, MD            
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States
Contact: Robin Chisholm     317-274-7679     rlchisho@iupui.edu    
Principal Investigator: Kieren Mather, MD            
United States, Louisiana
Tulane University Health Sciences Center Recruiting
New Orleans, Louisiana, United States
Contact: Pat Reilly     504-988-4651     preilly@tulane.edu    
Principal Investigator: Vivian Fonseca, MD            
United States, Massachusetts
Joslin Diabetes Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Elizabeth Tatro     617-735-1940     elizabeth.tatro@joslin.harvard.edu    
Contact: Allison B. Goldfine, MD     617-732-2643     allison.goldfine@joslin.harvard.edu    
Principal Investigator: Allison B. Goldfine, MD            
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48106
Contact: Cindy Plunkett     734-936-8065     cplunket@med.umich.edu    
Principal Investigator: Rodica Pop-Busui, MD            
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States
Contact: Sarah Kissel     314-362-8688     skissel@wustl.edu    
Principal Investigator: Janet McGill, MD            
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omana, Nebraska, United States
Contact: Peggy Karatoprakli     402-995-4163     peggy.karatoprakli@va.gov    
Principal Investigator: Cyrus Desouza, MD            
United States, New York
Columbia University Recruiting
New York City, New York, United States
Contact: Carlos Lopez Jimenez     212-305-2920     CL517@columbia.edu    
Contact: Leocar Mesa     (212) 305-8797     lm2537@columbia.edu    
Principal Investigator: Daniel Donovan, MD            
North Shore Diabetes and Endocrine Associates Recruiting
Ney Hyde Park, New York, United States
Contact: Mini Thomas     516-327-0850 ext 256     mthomas@nsdea.com    
Principal Investigator: Kenneth Hershon, MD            
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States
Contact: Janet Brown     718-405-8266     jabrown@aecom.yu.edu    
Principal Investigator: Jill Crandall, MD            
Lang Medical Center Recruiting
Queens, New York, United States
Contact: Maria Roccisano         mar9176@nyp.org    
Principal Investigator: Dan Lorber, MD            
United States, North Carolina
University of North Carolina Recruiting
Durham, North Carolina, United States
Contact: Gail Fuller     919-484-0931 ext 274     gail_fuller@med.unc.edu    
Principal Investigator: John Buse, MD            
Carolina's Health Care Recruiting
Charlotte, North Carolina, United States
Contact: Carol Morris     704-446-7736     carol.morris@carolinas.org    
Principal Investigator: Thomas Barringer, MD            
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States
Contact: Renee Smalley     214-648-9470     Renee.smalley@utsouthwestern.edu    
Principal Investigator: Phillip Raskin, MD            
Scott and White Recruiting
Temple, Texas, United States
Contact: Sarah Allenson     254-215-0306     sallenson@swmail.sw.org    
Principal Investigator: Veronica Piziak, MD            
Sponsors and Collaborators
Joslin Diabetes Center
Investigators
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 School of Medicine
Study Director: Kathleen Jablonski, PhD George Washington University
Study Director: Myrlene Staten, MD National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: Joslin Diabetes Center, Boston, MA ( Dr. Allison B. Goldfine, MD )
Study ID Numbers: CHS 06-20-2, UO1-DK074556
Study First Received: November 26, 2008
Last Updated: September 18, 2009
ClinicalTrials.gov Identifier: NCT00799643     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Joslin Diabetes Center:
Type 2 Diabetes Mellitus (T2D)
Inflammation
Obesity
Metabolic Syndrome
Salicylates

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Anti-Inflammatory Agents
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Physiological Effects of Drugs
Salicylsalicylic acid
Diabetes Mellitus
Sodium Salicylate
Endocrine System Diseases
Enzyme Inhibitors
Pharmacologic Actions
Inflammation
Pathologic Processes
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Glucose Metabolism Disorders
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010