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

Type 2 Diabetes Clinical Trial

— TINSAL-T2D  

Official title:

Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00392678
• Other study ID #: CHS 06-20, NIH U01 DK74556
• Secondary ID: U01DK074556
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 2006
• Est. completion date: December 2010

Study information

• Verified date: March 2019
• Source: Joslin Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: December 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Inflammation
• Type 2 Diabetes

Intervention

Drug:
• Salsalate
Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided
• Placebo
Placebo to Salsalate

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Joslin Diabetes Center	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008 Feb;31(2):289-94. Epub 2007 Oct 24. — View Citation

Goldfine AB, Fonseca V, Jablonski KA, Chen YD, Tipton L, Staten MA, Shoelson SE; Targeting Inflammation Using Salsalate in Type 2 Diabetes Study Team. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013 Jul 2;159(1):1-12. doi: 10.7326/0003-4819-159-1-201307020-00003. — View Citation

Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE; TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann — View Citation

Goldfine AB, Silver R, 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. Clin Transl Sci. 2008 May;1(1):36-43. doi: 10.1111/j.1752-8062.2008.00026.x. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1	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.	14 week
Secondary	Change in HbA1c	Change from baseline to either 14 or 26 weeks, or last HbA1c measurement prior to rescue therapy	14 week
Secondary	Change From Baseline and Trends in Fasting Glucose Over Time		14 week
Secondary	Change in Lipids	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); LDL-C/HDL-C ratio not calculated	14 week
Secondary	Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index	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.	Baseline, week 14
Secondary	Safety and Tolerability	See adverse event module for details. Safety and tolerability of salsalate compared to placebo as assessed by adverse events.	14 weeks
Secondary	Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index	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	Baseline, week 14

External Links

•   TINSAL-T2D website