Clinical trial NCT00379808: Study of the Arachidonate 5-Lipoxygenase Enzyme in Affecting the Risk for Coronary Heart Disease
Official title: Role of the Arachidonate 5-Lipoxygenase Pathway in Coronary Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Heart Disease
Keywords: coronary heart disease
montelukast
inflammation
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2006-09-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: High-sensitivity C-reactive Protein
timeFrame: 1 month
Secondary outcomes:
measure: High Density Lipoprotein (HDL)-Cholesterol
timeFrame: 1 month
Other outcomes:
measure: Triglycerides
timeFrame: 1 month
measure: Monocyte Chemotactic Protein-1 (MCP-1)
timeFrame: 1 month
measure: Interleukin 1 Receptor Antagonist (IL1ra)
timeFrame: 1 month
measure: Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78)
timeFrame: 1 month
Locations:
city: Gainesville
country: United States
facility: University of Florida Family Practice Medical Group Clinic
state: Florida
Study officials:
affiliation: University of Florida
name: Julie A Johnson, PharmD
role: PRINCIPAL_INVESTIGATOR
References: