Trial record 1 of 1 for:    NCT00799643
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Targeting Inflammation Using Salsalate for Type 2 Diabetes-stage II (TINSAL-T2D-II)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Allison Goldfine, Joslin Diabetes Center
ClinicalTrials.gov Identifier:
NCT00799643
First received: November 26, 2008
Last updated: March 25, 2014
Last verified: March 2014
  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 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 From Baseline, Compared Between Treatment Groups. [ Time Frame: 48 weeks from baseline ] [ Designated as safety issue: No ]
    HbA1c (%, percentage of HbA1c) change from baseline.


Secondary Outcome Measures:
  • Change From Baseline in Fasting Glucose Over Time. [ Time Frame: 48 weeks from baseline ] [ Designated as safety issue: Yes ]
  • 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 ]
  • 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 ]
  • 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 ]

Enrollment: 638
Study Start Date: November 2008
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799643

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States
United States, California
University of California, San Diego
San Diego, California, United States
United States, Connecticut
Chapel Medical Group
New Haven, Connecticut, United States
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States
Kaiser Permanente
Tucker, Georgia, United States
United States, Indiana
Indiana University
Indianapolis, Indiana, United States
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States
United States, Maryland
Medstar Research Institute
Hyattsville, Maryland, United States
Dr. Rudo, Westminster, MD
Westminster, Maryland, United States, 21157
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48106
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States
United States, Nebraska
University of Nebraska Medical Center
Omana, Nebraska, United States
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States
Columbia University
New York City, New York, United States
North Shore Diabetes and Endocrine Associates
Ney Hyde Park, New York, United States
Lang Medical Center
Queens, New York, United States
United States, North Carolina
Carolina's Health Care
Charlotte, North Carolina, United States
University of North Carolina
Durham, North Carolina, United States
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States
Scott and White
Temple, Texas, United States
Sponsors and Collaborators
Allison Goldfine
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
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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Allison Goldfine, Head Section of Clinical Research, Joslin Diabetes Center, Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00799643     History of Changes
Other Study ID Numbers: CHS 06-20-2, UO1-DK074556
Study First Received: November 26, 2008
Results First Received: September 13, 2013
Last Updated: March 25, 2014
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
Diabetes Mellitus, Type 2
Inflammation
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Sodium Salicylate
Salicylsalicylic acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 10, 2014