Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D) - Full Text View

Sponsor:	Joslin Diabetes Center
Collaborator:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	Joslin Diabetes Center
ClinicalTrials.gov Identifier:	NCT00392678

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. 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.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: Salsalate	Phase II Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Obesity

Drug Information available for: Sodium salicylate Salicylsalicylic acid

U.S. FDA Resources

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 14 (stage 1) or 26 (stage 2) in the intent-to-treat (ITT) population with last observation carried forward. [ Time Frame: 14-26 week ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	402
Study Start Date:	October 2006
Estimated Study Completion Date:	December 2010
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator	Drug: Salsalate Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
2: Active Comparator	Drug: Salsalate Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
3: Active Comparator	Drug: Salsalate Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
4: Active Comparator	Drug: Salsalate Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392678

Locations

United States, Connecticut
Chapel Medical Group
New Haven, Connecticut, United States
United States, District of Columbia
MedStar Research Institute
Washington DC, District of Columbia, United States
United States, Florida
Endocrine Clinical Research
Winter Park, Florida, United States
United States, Georgia
Emory School of Medicine
Atlanta, Georgia, United States
Kaiser Permanente
Atlanta, Georgia, United States
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States
United States, New York
Columbia University
New York City, New York, United States
Kaleida Health Center
Buffalo, New York, United States
North Shore Diabetes and Endocrine Associates
New Hyde Park, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States

Sponsors and Collaborators

Joslin Diabetes Center

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:	Steven E. Sheolson, 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

More Information

Additional Information:

TINSAL-T2D website This link exits the ClinicalTrials.gov site

Publications:

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. Review. Erratum in: J Clin Invest. 2006 Aug;116(8):2308.

Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults. Diabetes Care. 2007 Oct 24; [Epub ahead of print]

Goldfine AB, Silver S, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes, Clinical and Translational Science, 2008 May;1(1):36-43

Responsible Party:	Joslin Diabetes Center, Boston, MA ( Allison Goldfine, MD )
Study ID Numbers:	CHS 06-20, U01 DK074556
Study First Received:	October 25, 2006
Last Updated:	November 26, 2008
ClinicalTrials.gov Identifier:	NCT00392678 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; United States: Federal Government

Keywords provided by Joslin Diabetes Center:

Type 2 Diabetes
Inflammation
Obesity
Metabolic Syndrome

Additional relevant MeSH terms:

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
Diabetes Mellitus, Type 2
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