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

NCT00392678 | Completed Phase 2 Results DMC

• 2 other identifiers: CHS 06-20, NIH U01 DK74556U01DK074556
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 16

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.

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes; Inflammation; Obesity; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in HbA1c

  14 week

• Change From Baseline and Trends in Fasting Glucose Over Time

  14 week

• Change in Lipids

  14 week

• Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index

  Baseline, week 14

• Safety and Tolerability

  14 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo, appearance matched to active drug

Drug: Placebo

3 gram

ACTIVE COMPARATOR

Salsalate 3.0 grams daily, divided

Drug: Salsalate

3.5 gram

ACTIVE COMPARATOR

Salsalate 3.5 g daily, divided

Drug: Salsalate

4 gram

ACTIVE COMPARATOR

Salsalate 4.0 g daily, divided

Drug: Salsalate

Interventions

Salsalate DRUG

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

Also known as: Disalcid, Salicylsalicylic acid

3 gram; 3.5 gram; 4 gram

Placebo DRUG

Placebo to Salsalate

Also known as: Placebo to Salsalate

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• FPG ≤ 225 mg/dL and HbA1c\>7% and ≤9.5% at screening
• Age ≥18 and \<75
• Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm)

You may not qualify if:

• Type 1 diabetes and/or history of ketoacidosis determined by medical history
• History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation
• History of long-term therapy with insulin (\>30 days) within the last year
• Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4 (Byetta), alone or in combination in the previous 6 months
• Pregnancy or lactation
• Patients requiring corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks)
• 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
• Surgery within 30 days prior to screening
• 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.
• History of chronic liver disease including hepatitis B or C
• History of peptic ulcer or endoscopy demonstrated gastritis
• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
• 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
• New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (16)

Chapel Medical Group

New Haven, Connecticut, 06511, United States

Location

MedStar Research Institute

Washington D.C., District of Columbia, 20003-4393, United States

Location

Endocrine Clinical Research

Winter Park, Florida, 32746, United States

Location

Kaiser Permanente

Atlanta, Georgia, 30084, United States

Location

Emory School of Medicine

Atlanta, Georgia, 30303, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

Kaleida Health Center

Buffalo, New York, 14226, United States

Location

North Shore Diabetes and Endocrine Associates

New Hyde Park, New York, 11042, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (5)

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

  PMID: 16823477 BACKGROUND

• 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.

  PMID: 17959861 BACKGROUND

• 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.

  PMID: 19337387 BACKGROUND

• 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.

  PMID: 23817699 BACKGROUND

• 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.

  PMID: 20231565 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation; Obesity; Metabolic Syndrome

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Insulin Resistance; Hyperinsulinism

Results Point of Contact

• Title: Allison B. Goldfine, MD co-investigator
• Organization: Joslin Diabetes Center

allison.goldfine@joslin.harvard.edu

617-309-2643

Study Officials

• Steven E. Sheolson, MD, PhD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

• 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)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: October 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: December 1, 2010
• Last Updated: April 8, 2019
• Results First Posted: July 26, 2013

Record last verified: 2019-03

Locations

US (16)