Clinical trial NCT01960413: Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
Official title: Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (Also Known as the Montelukast Trial in Sickle Cell Anemia)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Medical College of Wisconsin
name: Versiti
First posted: 2013-10-10
Enrollment: 46
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)
timeFrame: baseline to eight weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Vanderbilt University Medical Center
name: Michael R. DeBaun, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Joshua Field, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Field JJ, Kassim A, Brandow A, Embury SH, Matsui N, Wilkerson K, Bryant V, Zhang L, Simpson P, DeBaun MR. Phase 2 trial of montelukast for prevention of pain in sickle cell disease. Blood Adv. 2020 Mar 24;4(6):1159-1165. doi: 10.1182/bloodadvances.2019001165.