Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia

Study Overview
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Brief Summary
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In this feasibility trial, the investigators will compare participants treated with montelukast and hydroxyurea to those treated with placebo and hydroxyurea for a total of 8 weeks.

Detailed Description
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The primary hypothesis for this trial is that montelukast adds efficacy to hydroxyurea therapy for improving vaso-occlusion when compared to hydroxyurea alone. The following specific aims will be tested in adolescents and adults with sickle cell disease (SCD): Aim 1. To determine whether montelukast versus placebo added to hydroxyurea will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with sickle cell disease. Aim 2. To evaluate physiologic effects of montelukast versus placebo added to hydroxyurea in adolescents and adults with sickle cell disease. Subaim 2A. To determine if montelukast versus placebo added to hydroxyurea will improve lung function in adolescents and adults with sickle cell disease. Subaim 2B. To determine if montelukast versus placebo added to hydroxyurea will improve forearm microvascular blood flow in adolescents and adults with sickle cell disease, respectively. Funding Source - FDA OOPD

Official Title
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Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (Also Known as the Montelukast Trial in Sickle Cell Anemia)

Conditions
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Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)

Intervention / Treatment
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* Drug: Montelukast added to Hydroxyurea
* Drug: Placebo added to Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis 2)Males and females age 16 years to 70 years old 3)Greater than 2 episodes of pain in the last 12 months 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin Exclusion Criteria: Judged not likely to be study compliant by his/her hematologist History of adverse reaction to montelukast or any of the components of montelukast Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days Chronic blood transfusion therapy defined as regularly scheduled transfusions. Hemoglobin A greater than15% on hemoglobin analysis Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate). Current participation in another therapeutic trial for SCD Known current pregnancy Known history of HIV Serum creatinine greater than 3 times the site's upper limit of normal

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Montelukast added to Hydroxyurea<br>Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment | Drug: Montelukast added to Hydroxyurea<br> <br> |
| Placebo Comparator: Placebo added to Hydroxyurea<br>Oral placebo taken daily for eight weeks with current hydroxyurea regiment | Drug: Placebo added to Hydroxyurea<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM) | The primary outcome measure is based on a 30% reduction, which would be  106 ng/ml reduction. The study was designed with 25 in each group in order to explore all three aims and potential confounders. However, if the investigators are not able to accrue 25 subjects in each arm, the investigators would still be able to detect a 30% difference in sVCAM with 17 subjects in each group. The 95% confidence interval for detecting a 30% difference is between 204 ng/ml and 290 ng/ml (or an 18-42% reduction in sVCAM). Importantly, the lower limit of the 95% confidence interval (18%) is still a clinically relevant reduction in sVCAM. Thus, if the investigators detect a 30% or larger difference in sVCAM in this study, the investigators will be assured that, based on the 95% confidence interval, these data are clinically important. | baseline to eight weeks |