Coronary Heart Disease
Conditions
Keywords
coronary heart disease, montelukast, inflammation
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.
Interventions
DRUGmontelukast
10 mg tablet (masked by capsule) daily for 1 month
DRUGPlacebo
1 lactose-containing capsule daily for 1 month
Sponsors
American Heart Association
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High-sensitivity C-reactive Protein | 1 month | measured in a CLIA clinical laboratory facility (Quest Diagnostics, Tampa, FL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High Density Lipoprotein (HDL)-Cholesterol | 1 month | Lipid levels were determined at a clinical laboratory (Quest Diagnostics) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Triglycerides | 1 month | measured by a clinical laboratory; Quest Laboratories |
| Monocyte Chemotactic Protein-1 (MCP-1) | 1 month | biomarker was measured by enzyme-linked immunosorbant assay (ELISA) |
| Interleukin 1 Receptor Antagonist (IL1ra) | 1 month | IL1ra was determined by enzyme-linked immunosorbant assay (ELISA) |
| Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78) | 1 month | biomarker determined by enzyme-linked immunosorbant assay. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited based on flyers posted in public places, through recontact of patients in previous studies, and patients cared for in a family medicine clinic
Participants by arm
| Arm | Count |
|---|---|
| All Participants Patients were randomized in a crossover design, but baseline characteristics were presented for all participants. Likewise data are not separated by order of treatment because there were no order effects | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intervention Period 2 (4 Weeks) | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age Continuous All study participants | 50.8 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 |
Outcome results
Primary
High-sensitivity C-reactive Protein
measured in a CLIA clinical laboratory facility (Quest Diagnostics, Tampa, FL)
Time frame: 1 month
Population: based on patients who completed the entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | High-sensitivity C-reactive Protein | 1.0 mg/dl |
| Montelukast | High-sensitivity C-reactive Protein | 1.0 mg/dl |
Comparison: Statistical power was calculated using G\*Power (Dusseldorf, Germany). Based on previously observed effects of statin drugs on hsCRP levels, 22 subjects provided 80% power to detect a moderate effect on hsCRP levels.p-value: 0.22Wilcoxon sign rank test
Secondary
High Density Lipoprotein (HDL)-Cholesterol
Lipid levels were determined at a clinical laboratory (Quest Diagnostics)
Time frame: 1 month
Population: those completing entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | High Density Lipoprotein (HDL)-Cholesterol | 52 mg/dl |
| Montelukast | High Density Lipoprotein (HDL)-Cholesterol | 50 mg/dl |
Comparison: Null hypothesis is that montelukast does not affect HDL. Not powered for this endpointp-value: 0.57Wilcoxon sign rank
Other Pre-specified
Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78)
biomarker determined by enzyme-linked immunosorbant assay.
Time frame: 1 month
Population: those completing the entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78) | 631 pg/ml |
| Montelukast | Epithelial Cell-derived Neutrophil-activating Peptide 78 (ENA-78) | 527 pg/ml |
Comparison: null hypothesis is that montelukast does not affect ENA-78. The study is not powered to this biomarkerp-value: 0.09wilcoxon sign rank
Other Pre-specified
Interleukin 1 Receptor Antagonist (IL1ra)
IL1ra was determined by enzyme-linked immunosorbant assay (ELISA)
Time frame: 1 month
Population: all participants who completed the entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Interleukin 1 Receptor Antagonist (IL1ra) | 518 pg/ml |
| Montelukast | Interleukin 1 Receptor Antagonist (IL1ra) | 587 pg/ml |
Comparison: null hypothesis is that montelukast does not affect IL1ra.p-value: 0.03wilcoxon sign rank test
Other Pre-specified
Monocyte Chemotactic Protein-1 (MCP-1)
biomarker was measured by enzyme-linked immunosorbant assay (ELISA)
Time frame: 1 month
Population: those who completed the entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Monocyte Chemotactic Protein-1 (MCP-1) | 84 pg/ml |
| Montelukast | Monocyte Chemotactic Protein-1 (MCP-1) | 94 pg/ml |
Comparison: null hypothesis is that montelukast does not affect MCP-1. Study not powered to the biomarker.p-value: 0.12Wilcoxon
Other Pre-specified
Triglycerides
measured by a clinical laboratory; Quest Laboratories
Time frame: 1 month
Population: those completing the entire study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Triglycerides | 94 mg/dl |
| Montelukast | Triglycerides | 104 mg/dl |
Comparison: The null hypothesis is that montelukast does not affect triglycerides. The study was not powered to this outcome measure.p-value: 0.33wilcoxon sign rank