Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
Conditions
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
Interventions
DRUGMontelukast added to Hydroxyurea
DRUGPlacebo added to Hydroxyurea
Sponsors
Medical College of Wisconsin
Versiti Blood Health
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Montelukast Added to Hydroxyurea Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment
Montelukast added to Hydroxyurea | 24 |
| Placebo Added to Hydroxyurea Oral placebo taken daily for eight weeks with current hydroxyurea regiment
Placebo added to Hydroxyurea | 22 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Montelukast Added to Hydroxyurea | Total | Placebo Added to Hydroxyurea |
|---|---|---|---|
| Age, Continuous | 29.25 years STANDARD_DEVIATION 10.46 | 29.95 years STANDARD_DEVIATION 10.27 | 30.76 years STANDARD_DEVIATION 10.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 45 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 42 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 24 participants | 46 participants | 22 participants |
| Sex: Female, Male Female | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 19 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 10 / 24 | 12 / 22 |
| serious Total, serious adverse events | 4 / 24 | 2 / 22 |
Outcome results
Primary
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.
Time frame: baseline to eight weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Montelukast Added to Hydroxyurea | Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM) | -3.2 ng/mL |
| Placebo Added to Hydroxyurea | Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM) | 4.17 ng/mL |