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

Vanderbilt University Medical Center

Status and phase: Completed; Phase 2

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

Treatments: Drug: Placebo added to Hydroxyurea; Drug: Montelukast added to Hydroxyurea

Study type: Interventional

Funder types: Other

Identifiers

NCT01960413

R01FD004117

Details and patient eligibility

About

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.

Full description

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

Enrollment: 46 patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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46 participants in 2 patient groups, including a placebo group

Montelukast added to Hydroxyurea

Experimental group

Description:

Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment

Treatment:

Drug: Montelukast added to Hydroxyurea

Placebo added to Hydroxyurea

Placebo Comparator group

Description:

Oral placebo taken daily for eight weeks with current hydroxyurea regiment

Treatment:

Drug: Placebo added to Hydroxyurea