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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

October 25, 2006
July 25, 2013
October 2006
July 2008   (final data collection date for primary outcome measure)
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 ]
The primary outcome for the TINSAL-T2D study is change in HbA1c level from baseline to week 26 in the intent-to-treat (ITT) population with last observation carried forward.
Complete list of historical versions of study NCT00392678 on ClinicalTrials.gov Archive Site
  • 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
  • Change from baseline to either 26 weeks or last HbA1c measurement prior to rescue therapy
  • Trends in HbA1c over time
  • Change from baseline and trends in fasting glucose over time
  • 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%
  • 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)
  • Change in insulin sensitivity (insulin, C-peptide, homeostasis model [HOMA] index)
  • Response rates for exceeding hyperglycemic targets between active and placebo treated groups
  • Need for rescue therapy
  • Need for discontinuation of study medication
  • Response rates in patients initially treated with lifestyle modification, insulin secretagogue, metformin or combination therapy
  • Response rates for a reduction in HbA1c for obese vs non-obese participants
  • Safety and tolerability of salsalate compared to placebo
Not Provided
Not Provided
 
Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D)
Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Type 2 Diabetes
  • Drug: Salsalate
    Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
    Other Name: Disalsid
  • Drug: Placebo
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
  • Active Comparator: Salsalate 3.0 g daily, divided
    Salsalate 3.0 grams daily, divided
    Intervention: Drug: Salsalate
  • Active Comparator: Salsalate 3.5 g daily, divided
    Salsalate 3.5 g daily, divided
    Intervention: Drug: Salsalate
  • Active Comparator: Salsalate 4.0 g daily, divided
    Salsalate 4.0 g daily, divided
    Intervention: Drug: Salsalate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
277
December 2010
July 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00392678
CHS 06-20, NIH U01 DK74556, U01DK074556
Yes
Allison Goldfine, Joslin Diabetes Center
Allison Goldfine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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)
Joslin Diabetes Center
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP