Targeting Inflammation Using Salsalate in CardioVascular Disease

NCT00624923 | Completed Phase 2 Results DMC

• 4 other identifiers: CHS 06-13P50HL083813CCI: 2006-P-00175CHS: 06-13
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 5

Brief Summary

The hypothesis is that western lifestyle, with sedentary behaviors and caloric excess promote a chronic, subacute inflammatory state that participates in the development and progression of atherosclerosis. We will evaluate the effects of targeting inflammation using the anti-inflammatory drug salsalate, compared to placebo, on coronary artery plaque volume assessed by multi-detector computed tomographic angiography (MDCTA). The TINSAL-CVD study is a randomized, double-masked, placebo-controlled, 2 arm, clinical trial. The purpose of the study is to compare the effect of salsalate or placebo on sub-acute inflammation and coronary plaque, in people with cardiovascular disease. Participants are randomized to active intervention (salsalate) or placebo interventions for a period of 30 months. The primary endpoint is change in plaque volume in the coronary arteries assessed by MDCTA from baseline to 30 months.

Conditions

Coronary Artery Disease; Overweight

Keywords

Coronary Artery Disease; Inflammation; Overweight; Metabolic Syndrome; Salsalate

Outcome Measures

Primary Outcomes (1)

• Change in Non-calcified Plaque Volume in the Coronary Arteries Assessed by MDCTA From Baseline to 30 Months

  Baseline to 30 months

Secondary Outcomes (3)

• Change in Cholesterol

  Baseline to 30 mo

• Change in Inflammation Marker: CRP

  baseline to 30 mo

• Change in Inflammation in the Liver Associated With Nonalcoholic Steatohepatitis (NASH), ALT

  baseline to 30 mo

Study Arms (2)

1- Active Pharmacologic

EXPERIMENTAL

Salsalate

Drug: Salsalate

2- Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Salsalate DRUG

Salsalate, 500 mg, seven tablets daily by mouth, divided into two doses, for 30 months

Also known as: Disalcid

1- Active Pharmacologic

Placebo DRUG

Placebo matched to Salsalate, seven tablets daily by mouth, divided into two doses, for 30 months

Also known as: Placebo to Salsalate

2- Placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility will be based upon the presence of established coronary artery disease including
• previous myocardial infarction (≥6 months ago), or
• previous coronary bypass surgery (\> 12 months ago), or
• stable angina, or
• significant non-calcified plaque in at least one coronary artery, or
• abnormal exercise tolerance test or
• an area of reversible ischemia on nuclear imaging study or pharmacologic stress, with subsequent revascularization, or angioplasty, or
• Transient cavity dilation
• More than one vascular territory involved with reversible defect (multiple defects)
• Reversible defects involving the anterior wall, septum or apex (LAD territory)
• More than one vascular territory involved with inducible wall motion abnormalities (multiple defects)
• Inducible wall motion abnormalities involving the anterior wall, septum or apex (LAD territory)
• Subjects should be at list 6 months after a myocardial infarction and/or revascularization procedure to be eligible.
• In addition, subjects must be:
• aged 21- 75 years inclusive,

You may not qualify if:

• Unstable angina (increase in frequency or severity of anginal episodes or development of chest pain at rest)
• significant obstructive disease (≥ 70%) in left main coronary artery, ostial LAD or three-vessel disease by MDCTA
• Significant heart failure (NYHA class III and IV)
• Current atrial fibrillation or Wolf-Parkinson-White (WPW) syndrome
• Allergy to beta-blocker in subjects with resting heart rate \> 65 bpm
• Systolic blood pressure \> 160 mm Hg
• Diastolic BP \> 100 mm Hg
• Persons with allergies to contrast material
• History of asthma if unable to tolerate beta blocker
• Allergy to iodinated contrast material or shellfish
• Allergy to nitroglycerin
• BMI \> 35 kg/m2 if female and \> 40 kg/m2 if male
• Body weight \> 350 lbs
• Use of drugs for weight loss \[e.g. Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the counter medications\] within three months of screening
• Surgery within 30 days of screening

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• Beth Israel Deaconess Medical Center: collaborator
• Tufts Medical Center: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

Seacoast Cardiology

York Village, Maine, 03939, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Heart Center of Metrowest

Framingham, Massachusetts, 01702, United States

Location

South Shore Internal Medicine

Milton, Massachusetts, 02186, United States

Location

Newton-Wellesley Cardiology

Newton, Massachusetts, 02462, United States

Location

Related Publications (11)

• 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 BACKGROUND

• Goldfine AB, Conlin PR, Halperin F, Koska J, Permana P, Schwenke D, Shoelson SE, Reaven PD. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia. 2013 Apr;56(4):714-23. doi: 10.1007/s00125-012-2819-3. Epub 2013 Jan 31.

  PMID: 23370525 BACKGROUND

• Avadhani R, Fowler K, Barbato C, Thomas S, Wong W, Paul C, Aksakal M, Hauser TH, Weinger K, Goldfine AB. Glycemia and cognitive function in metabolic syndrome and coronary heart disease. Am J Med. 2015 Jan;128(1):46-55. doi: 10.1016/j.amjmed.2014.08.025. Epub 2014 Sep 16.

  PMID: 25220612 BACKGROUND

• Goldfine AB, Shoelson SE. Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk. J Clin Invest. 2017 Jan 3;127(1):83-93. doi: 10.1172/JCI88884. Epub 2017 Jan 3.

  PMID: 28045401 BACKGROUND

• Ridker PM. Informative Neutral Studies Matter-Why the Targeting Inflammation With Salsalate in Cardiovascular Disease (TINSAL-CVD) Trial Deserves Our Attention. JAMA Cardiol. 2016 Jul 1;1(4):423-4. doi: 10.1001/jamacardio.2016.0604. No abstract available.

  PMID: 27438318 BACKGROUND

• Hauser TH, Salastekar N, Schaefer EJ, Desai T, Goldfine HL, Fowler KM, Weber GM, Welty F, Clouse M, Shoelson SE, Goldfine AB; Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) Study Team. Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins. JAMA Cardiol. 2016 Jul 1;1(4):413-23. doi: 10.1001/jamacardio.2016.0605.

  PMID: 27438317 RESULT

• Day EA, Ford RJ, Smith BK, Houde VP, Stypa S, Rehal S, Lhotak S, Kemp BE, Trigatti BL, Werstuck GH, Austin RC, Fullerton MD, Steinberg GR. Salsalate reduces atherosclerosis through AMPKbeta1 in mice. Mol Metab. 2021 Nov;53:101321. doi: 10.1016/j.molmet.2021.101321. Epub 2021 Aug 21.

  PMID: 34425254 DERIVED

Related Links

• This site provides information on a related clinical trial to target inflammation using salsalate to lower blood glucose in patients with type 2 diabetes mellitus.
• Home page for Joslin Diabetes Center, Boston, MA.

MeSH Terms

Conditions

Coronary Artery Disease; Overweight; Inflammation; Metabolic Syndrome

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Results Point of Contact

• Title: Dr. Allison Goldfine
• Organization: Joslin Diabetes Center

allison.goldfine@joslin.harvard.edu

617-309-2400

Study Officials

• Francine Welty, MD

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

• Allison B. Goldfine, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

• Ernest Schaefer, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

• Melvin Clouse, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Steven E. Shoelson, MD, PhD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2008
• First Posted: February 28, 2008
• Study Start: September 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: July 1, 2016
• Last Updated: May 7, 2019
• Results First Posted: December 12, 2017

Record last verified: 2019-04

Locations

US (5)