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

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

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:

1. Judged not likely to be study compliant by his/her hematologist

2. History of adverse reaction to montelukast or any of the components of montelukast

3. Have used medications known to interact with montelukast such as rifampin,
phenobarbital, and gemfibrozil within 4 weeks of enrollment

4. Currently being treated with a leukotriene antagonist (montelukast or zileuton) or
have used montelukast/zileuton within the last 60 days

5. Chronic blood transfusion therapy defined as regularly scheduled transfusions.

6. Hemoglobin A greater than15% on hemoglobin analysis

7. 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).

8. Current participation in another therapeutic trial for SCD

9. Known current pregnancy

10. Known history of HIV

11. Serum creatinine greater than 3 times the site's upper limit of normal