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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Allison Goldfine, Joslin Diabetes Center
ClinicalTrials.gov Identifier:
NCT00392678
First received: October 25, 2006
Last updated: July 25, 2013
Last verified: July 2013
  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 first stage is a dose ranging study, administering salsalate compared to placebo over three months. 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.

The second stage is a second trial and posted under alternate registration.


Condition Intervention Phase
Type 2 Diabetes
Drug: Salsalate
Drug: 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 14 (Stage 1) in the Intent-to-treat (ITT) Population With Last Observation Carried Forward. [ Time Frame: 14 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline to Either 14 or 26 Weeks, or Last HbA1c Measurement Prior to Rescue Therapy [ Time Frame: 14 week ] [ Designated as safety issue: No ]
    see primary outcome

  • Change From Baseline and Trends in Fasting Glucose Over Time [ Time Frame: 14 week ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    This was an aim proposed for the longer duration study and is reported under TINSAL-T2D stage 2.

  • 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 week ] [ Designated as safety issue: No ]
    LDL-C/HDL-C ratio not calculated

  • Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index [ Time Frame: Baseline, week 14 ] [ Designated as safety issue: No ]
    HOMA-IR was not calcuated due to potential confounding effect of salicylates to inhibit insulin clearance. Change in insulin from Baseline to Week 14 in data table below.

  • Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups [ Time Frame: 14 week ] [ Designated as safety issue: No ]
    Please see adverse events module for hyperglycemia.

  • Need for Rescue Therapy [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.

  • Need for Discontinuation of Study Medication [ Time Frame: 14 week ] [ Designated as safety issue: No ]
    This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.

  • Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy [ Time Frame: 14-26 week ] [ Designated as safety issue: No ]
    This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.

  • Response Rates for a Reduction in HbA1c for Obese vs Non-obese Participants [ Time Frame: 14-26 week ] [ Designated as safety issue: No ]
    This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.

  • Safety and Tolerability of Salsalate Compared to Placebo as Assessed by Adverse Events. [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    See adverse event module for details.

  • Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index [ Time Frame: Baseline, week 14 ] [ Designated as safety issue: No ]
    HOMA-IR was not calcuated due to potential confounding effect of salicylates to inhibit insulin clearance. Change in C-peptide from Baseline to Week 14 is in the data table below


Enrollment: 277
Study Start Date: October 2006
Study Completion Date: December 2010
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Active Comparator: Salsalate 3.0 g daily, divided
Salsalate 3.0 grams daily, divided
Drug: Salsalate
Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
Other Name: Disalsid
Active Comparator: Salsalate 3.5 g daily, divided
Salsalate 3.5 g daily, divided
Drug: Salsalate
Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
Other Name: Disalsid
Active Comparator: Salsalate 4.0 g daily, divided
Salsalate 4.0 g daily, divided
Drug: Salsalate
Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
Other Name: Disalsid

Detailed Description:

The primary objective of the first stage of the TINSAL-T2D trial is to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. The trial is a multicenter, single mask lead-in, double masked placebo controlled dose ranging study, comparing salsalte to placebo over 3 months.

  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, 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.
  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. Type 1 diabetes and/or history of ketoacidosis determined by medical history
  2. History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation
  3. History of long-term therapy with insulin (>30 days) within the last year
  4. Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4 (Byetta), alone or in combination in the previous 6 months
  5. Pregnancy or lactation
  6. Patients requiring corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks)
  7. 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
  8. Surgery within 30 days prior to screening
  9. 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.
  10. History of chronic liver disease including hepatitis B or C
  11. History of peptic ulcer or endoscopy demonstrated gastritis
  12. History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
  13. 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
  14. New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure
  15. History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months
  16. 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)
  17. 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)
  18. Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening
  19. Platelets <100,000 cu mm at screening.
  20. AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening
  21. Total Bilirubin >1.50 x ULN at screening
  22. Triglycerides (TG) >500 mg/dL at screening
  23. Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study
  24. Previous allergy to aspirin
  25. Chronic or continuous use (daily for more than 7 days) of nonsteroidal anti-inflammatory drugs within the preceding 2 months
  26. Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants
  27. Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents
  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: NCT00392678

Locations
United States, Connecticut
Chapel Medical Group
New Haven, Connecticut, United States, 06511
United States, District of Columbia
MedStar Research Institute
Washington DC, District of Columbia, United States, 20003-4393
United States, Florida
Endocrine Clinical Research
Winter Park, Florida, United States, 32746
United States, Georgia
Emory School of Medicine
Atlanta, Georgia, United States, 30303
Kaiser Permanente
Atlanta, Georgia, United States, 30084
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68105
United States, New York
Kaleida Health Center
Buffalo, New York, United States, 14226
North Shore Diabetes and Endocrine Associates
New Hyde Park, New York, United States, 11042
Columbia University
New York City, New York, United States, 10032
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Allison Goldfine
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
Study Director: Kathleen Jablonski, PhD George Washington University
Study Director: Myrlene Staten, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: Allison Goldfine, Study Co-Principal Investigator, Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00392678     History of Changes
Other Study ID Numbers: CHS 06-20, NIH U01 DK74556, U01DK074556
Study First Received: October 25, 2006
Results First Received: February 20, 2013
Last Updated: July 25, 2013
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:
Diabetes Mellitus, Type 2
Inflammation
Diabetes Mellitus
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 October 16, 2014