Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II

NCT00799643 | Completed Phase 2 Results DMC

• 2 other identifiers: CHS 06-20-2U01DK074556
• Study Type: interventional
• Target: 638
• Locations: 1 country
• Sites: 21

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. Enrollment in the first stage is complete. The primary objective of the first stage was to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus (T2D); Inflammation; Obesity; Metabolic Syndrome; Salicylates

Outcome Measures

Primary Outcomes (1)

• The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups.

  HbA1c (%, percentage of HbA1c) change from baseline.

  48 weeks from baseline

Secondary Outcomes (6)

• Change From Baseline in Fasting Glucose Over Time.

  48 weeks from baseline

• 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%

  24 and 48 weeks

• 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)

  48 weeks

• Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers

  24 and 48 weeks

• Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication

  24 and 48 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

Salsalate, 3.5 g/d orally, divided dosing

Drug: Salsalate

2

PLACEBO COMPARATOR

Salsalate Placebo, orally, divided dosing

Drug: Salsalate Placebo

Interventions

Salsalate DRUG

Salsalate 3.5 g/d orally, divided dosing

Also known as: disalsid

1

Salsalate Placebo DRUG

2

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 (including SFU, non-SFU, and dipeptidyl peptidase IV (DPP-4) inhibitors), alpha-glucosidase inhibitors, or bile acid sequestrants (dosed once per day such that study drug can be administered ≥ 4 hours prior to sequestrant); or a combination of up to two of these at maximal dose. Dosing must be stable for 8 weeks prior to screening. Participant must have been diagnosed with T2D at least 8 weeks before screening.
• 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:

• No prior participation in Stage I of TINSAL-T2D ; exception: a participant who failed screening for HbA1c in Stage I will be allowed to re-screen for Stage II.
• 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), alone or in combination in the previous 6 months; or exendin-4 (Byetta), alone or in combination in the previous 3 months
• Pregnancy or lactation
• Patients requiring oral 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

Sponsors & Collaborators

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

Study Sites (21)

University of Alabama

Birmingham, Alabama, United States

Location

University of California, San Diego

San Diego, California, United States

Location

Chapel Medical Group

New Haven, Connecticut, United States

Location

Emory University School of Medicine

Atlanta, Georgia, United States

Location

Kaiser Permanente

Tucker, Georgia, United States

Location

Indiana University

Indianapolis, Indiana, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Location

Medstar Research Institute

Hyattsville, Maryland, United States

Location

Dr. Rudo, Westminster, MD

Westminster, Maryland, 21157, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, United States

Location

North Shore Diabetes and Endocrine Associates

New Hyde Park, New York, United States

Location

Columbia University

New York, New York, United States

Location

Lang Medical Center

Queens, New York, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, United States

Location

Carolina's Health Care

Charlotte, North Carolina, United States

Location

University of North Carolina

Durham, North Carolina, United States

Location

University of Texas Southwestern

Dallas, Texas, United States

Location

Scott and White

Temple, Texas, United States

Location

Related Publications (6)

• 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, 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 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 RESULT

• Goldfine AB, Buck JS, Desouza C, Fonseca V, Chen YD, Shoelson SE, Jablonski KA, Creager MA; TINSAL-FMD (Targeting Inflammation Using Salsalate in Type 2 Diabetes-Flow-Mediated Dilation) Ancillary Study Team. Targeting inflammation using salsalate in patients with type 2 diabetes: effects on flow-mediated dilation (TINSAL-FMD). Diabetes Care. 2013 Dec;36(12):4132-9. doi: 10.2337/dc13-0859. Epub 2013 Oct 15.

  PMID: 24130358 DERIVED

Related Links

• description of trial for patients and medical professionals

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
• Organization: Joslin Diabetes Center

allison.goldfine@joslin.harvard.edu

617-309-2400

Study Officials

• Steven E. Shoelson, 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 & Digestive & 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: November 26, 2008
• First Posted: December 1, 2008
• Study Start: November 1, 2008
• Primary Completion: September 1, 2012
• Last Updated: December 11, 2017
• Results First Posted: November 25, 2013

Record last verified: 2017-11

Locations

US (21)