Study of the Arachidonate 5-Lipoxygenase Enzyme in Affecting the Risk for Coronary Heart Disease

Role of the Arachidonate 5-Lipoxygenase Pathway in Coronary Heart Disease

The purpose of this study is to determine whether a particular substance involved in inflammation, called leukotrienes, is involved in causing heart disease to occur or to progress.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: Placebo; Drug: montelukast

Detailed Description

The focus of this study is to better understand why some adults develop heart disease and others do not. There are many known factors which play a role in causing heart disease, such as diet and lifestyle. Also, we know that inflammation, a process in the body which causes painful joints in arthritis or swelling at a site if injury, also contributes to heart disease. In particular, we will address whether leukotrienes, a component of inflammation, is involved in promoting heart disease. We will study this by giving subjects at high risk for heart disease a drug called montelukast which causes leukotrienes to have a reduced effect in the body. In addition for comparison, we will give other subjects a placebo for the same amount of time. These subjects will then be crossed-over and will receive either montelukast or placebo depending on which treatment they received first. We will compare these subjects using blood tests to see if subjects who take montelukast show signs of less inflammation caused by early heart disease as compared to subjects who do not.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32601
      • University of Florida Family Practice Medical Group Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Current hypertension (blood pressure > 140/90 mmHg) or current use of anti-hypertensive medications AND

Exclusion Criteria:

• Current use of lipid-lowering medications
• Current use of montelukast
• Poorly controlled hypertension, where systolic blood pressure is greater than 160 or diastolic blood pressure is greater than 100
• Use of steroid drugs, non-steroidal anti-inflammatory drugs or other anti-inflammatory medications in the two weeks prior to enrollment. (low dose aspirin ( < 325 mg) is OK, but indication must be cardiovascular)
• Current recreational drug use
• Other cardiovascular disease or previous cardiovascular event. These include:
• history of angina pectoris
• history of heart failure
• presence of a cardiac pacemaker
• history of myocardial infarction
• previous revascularization procedure
• history cerebrovascular disease including stroke and transient ischemic attack
• Pregnancy or lactation
• Diabetes mellitus
• Lactose intolerance
• Contraindications to montelukast therapy
• Alcoholism
• Known hepatic disease
• Existing chronic obstructive pulmonary disease, asthma, allergic rhinitis
• Active chronic immune, infectious, neoplastic or inflammatory diseases requiring therapy (such as active Hepatitis B, Hepatitis C, human immunodeficiency virus (HIV))
• Immunosuppressant therapy or known immunosuppression due to disease high density lipoprotein (HDL) < 40 mg/dL (although this would be a risk factor for heart disease, because of preliminary data which indicates that montelukast may lower HDL levels, we will exclude patients with abnormally low HDL from study)
• Other criteria at investigator discretion that are deemed to make the subject a poor candidate for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 1 lactose-containing capsule daily for 1 month	Drug: Placebo; 1 lactose-containing capsule daily for 1 month
Active Comparator: Montelukast 10 mg; 1 montelukast 10 mg tablet (masked by capsule) daily for 1 month	Drug: montelukast; 10 mg tablet (masked by capsule) daily for 1 month; Other Names: Singulair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-sensitivity C-reactive Protein	measured in a CLIA clinical laboratory facility (Quest Diagnostics, Tampa, FL)	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High Density Lipoprotein (HDL)-Cholesterol	Lipid levels were determined at a clinical laboratory (Quest Diagnostics)	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Triglycerides	measured by a clinical laboratory; Quest Laboratories	1 month
Monocyte Chemotactic Protein-1 (MCP-1)	biomarker was measured by enzyme-linked immunosorbant assay (ELISA)	1 month
Interleukin 1 Receptor Antagonist (IL1ra)	IL1ra was determined by enzyme-linked immunosorbant assay (ELISA)	1 month
Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78)	biomarker determined by enzyme-linked immunosorbant assay.	1 month

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: American Heart Association

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: September 20, 2006
• First Submitted That Met QC Criteria: September 20, 2006
• First Posted (Estimate): September 22, 2006

Study Record Updates

• Last Update Posted (Estimate): July 23, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: inflammation; coronary heart disease; montelukast
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 06011312; AHA0615253B (Other Grant/Funding Number: American Heart Associatino)