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

NCT ID: NCT00392678

Last Updated: 2019-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2010-12-31

Brief 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.

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo, appearance matched to active drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to Salsalate

3 gram

Salsalate 3.0 grams daily, divided

Group Type: ACTIVE_COMPARATOR

Salsalate

Intervention Type: DRUG

Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

3.5 gram

Salsalate 3.5 g daily, divided

Group Type: ACTIVE_COMPARATOR

Salsalate

Intervention Type: DRUG

Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

4 gram

Salsalate 4.0 g daily, divided

Group Type: ACTIVE_COMPARATOR

Salsalate

Intervention Type: DRUG

Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

Interventions

Salsalate

Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

Intervention Type: DRUG

Placebo

Placebo to Salsalate

Intervention Type: DRUG

Other Intervention Names

Disalcid; Salicylsalicylic acid; Placebo to Salsalate

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Joslin Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven E. Sheolson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Joslin Diabetes Center

Allison B. Goldfine, MD

Role: STUDY_DIRECTOR

Joslin Diabetes Center

Vivian Fonseca, MD

Role: STUDY_DIRECTOR

Tulane University

Kathleen Jablonski, PhD

Role: STUDY_DIRECTOR

George Washington University

Myrlene Staten, MD

Role: STUDY_DIRECTOR

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

Locations

Chapel Medical Group

New Haven, Connecticut, United States

MedStar Research Institute

Washington D.C., District of Columbia, United States

Endocrine Clinical Research

Winter Park, Florida, United States

Kaiser Permanente

Atlanta, Georgia, United States

Emory School of Medicine

Atlanta, Georgia, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Tulane University

New Orleans, Louisiana, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Kaleida Health Center

Buffalo, New York, United States

North Shore Diabetes and Endocrine Associates

New Hyde Park, New York, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

University of Texas Southwestern

Dallas, Texas, United States

Countries

United States

References

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.

Reference Type: BACKGROUND

PMID: 16823477 (View on PubMed)

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. doi: 10.2337/dc07-1338. Epub 2007 Oct 24.

Reference Type: BACKGROUND

PMID: 17959861 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19337387 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23817699 (View on PubMed)

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 Intern Med. 2010 Mar 16;152(6):346-57. doi: 10.7326/0003-4819-152-6-201003160-00004.

Reference Type: RESULT

PMID: 20231565 (View on PubMed)

Other Identifiers

U01DK074556

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHS 06-20, NIH U01 DK74556

Identifier Type: -

Identifier Source: org_study_id