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

Phase 2

Completed

Interventions: Drug: Montelukast added to Hydroxyurea
Drug: Placebo added to Hydroxyurea

Brief Summary: 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: 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

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Montelukast added to Hydroxyurea	Montelukast added to Hydroxyurea	Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment
Placebo added to Hydroxyurea	Placebo added to Hydroxyurea	Oral placebo taken daily for eight weeks with current hydroxyurea regiment

Primary Outcome Measures

Name	Time	Method
Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)	baseline to eight weeks	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.

Secondary Outcome Measures

Name	Time	Method

Locations (2): Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States