The study team proposes a triple-blind, placebo-controlled, phase II clinical trial of once-daily inhaled mometasone for 48 weeks (with 4-week washout at study completion) in individuals with Sickle Cell Disease (SCD) who report episodic cough or wheeze (ECW) but do not have asthma. Patients will be recruited from and followed in SCD clinics at participating sites. The primary endpoint will be a reduction in sVCAM level of 20% or more in comparison to placebo.
Dose rationale: Mometasone furoate 220mcg dry powder inhalation is a low-moderate ICS dose that can be given once daily. Higher doses can have systemic effects and systemic glucocorticoids can precipitate rebound SCD pain when discontinued. Adaptive, covariate-balanced randomization: While the sample size of the study will be fixed at 80 participants, instead of standard blocked or stratified randomization, the study team will use adaptive covariate-balanced randomization to minimize imbalance of important covariates. This will reduce the need to use multivariable techniques (which perform poorly in small samples) to adjust post hoc for differences between treatment groups. Covariates will include age, use of hydroxyurea, previous rate of Emergency Department (ED) utilization for SCD pain, and recruitment site. Follow up Schedule: There will be in-person visits every 8 weeks. In addition, a blinded research coordinator will contact participants by phone at 2-weeks and 4-weeks after enrollment and 4-weeks after each in-person follow up to encourage protocol adherence and collect data about adverse events and healthcare utilization. Post-protocol observation period: The study will be complete at 48 weeks. A final follow up visit will occur at 52 weeks (4-weeks after study protocol completed) to collect pain diary and adverse event data and to identify the proportion of the ICS group who want to continue ICS. In the event that individuals wish to continue ICS, the PI will contact the participant's treating physician to discuss. Data elements: A wide range of clinical and translational data will be collected during the study. Baseline data will include demographic and clinical variables regarding SCD severity, previous complications and respiratory surveys. Blood will be collected for standard-of-care labs and analysis of serum inflammatory cytokines. Pulmonary function testing including spirometry and Exhaled Nitric Oxide (eNO) will be performed. Health related quality of life will be collected via ASCQ-Me survey. Patients will also be followed with follow-up phone calls and prospective chart review for one year to identify hospital visits and other SCD complications. Procedures for collection of clinical and laboratory data: Data collection and management: Case report forms are provided as an appendix. Data will be entered into a REDCap database, which will be monitored by the Data Coordinating Team (DCT) (led by Co-I Gelijns) for completion and timeliness.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Once daily inhaled placebo for 48 weeks
Inhaled Mometasone for 48 weeks (with 4-week washout at study completion)
Mount Sinai St Luke's
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Soluble Vascular Cell Adhesion Molecule (sVCAM) level
Change in sVCAM level at one year compared to baseline. sVCAM is a biomarker used as a surrogate for red blood cell (RBC) adhesivity and overall disease severity in SCD.
Time frame: Baseline and one year
Reticulocyte Count level
Change in Reticulocyte Count level at one year compared to baseline. Reticulocyte count is a secondary measure of hemolysis. In SCD, it is more reflective of hemolytic burden than any other clinically available laboratory test.
Time frame: Baseline and one year
Plasma Free Hemoglobin level
Change in Free Hemoglobin level at one year compared to baseline. Free hemoglobin is a direct measure of hemolysis. It is more reflective of hemolytic burden than reticulocyte count but it is not available for clinical use.
Time frame: Baseline and one year
LDH level
Change in LDH level at one year compared to baseline. LDH is a marker of hemolysis
Time frame: Baseline and one year
Bilirubin (Direct and Indirect) level
Change in Bilirubin level at one year compared to baseline. Bilirubin measure of hemolysis
Time frame: Baseline and one year
Hemoglobin level
Change in Hemoglobin level at one year compared to baseline. Hemoglobin is a clinical lab test
Time frame: Baseline and one year
Leukocyte Count level
Change in Leukocyte level at one year compared to baseline. Leukocyte is a clinical lab test
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline and one year
Platelet Count level
Change in Platelet count level at one year compared to baseline. Platelet count is a clinical lab test
Time frame: Baseline and one year
Exhaled Nitric Oxide
Change in eNO level at one year as compared to baseline. Nitric oxide is a marker of eosinophilic pulmonary inflammation
Time frame: Baseline and one year
Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) survey
ASCQ-Me is a patient-reported outcome measurement system that evaluates and monitors the physical, mental, and social well-being of adults with sickle cell disease (SCD). ASCQ-Me uses a T-score metric in which 50 is the mean of the reference population and 10 is the standard deviation (SD) of that population.
Time frame: Baseline and one year
Medication Adherence Self-Report Scale for Asthma (MARS-A)
MARS-A is a 10-item, self-reported measure of adherence
Time frame: At one year
Brain Natriuretic Peptide
Change in brain natriuretic peptide at one year compared to baseline. Brain natriuretic peptide is a measure of atrial stretch.
Time frame: Baseline and one year
Spirometry
Change in spirometry at one year compared to baseline. Spirometry is the measure of airflow and lung function.
Time frame: Baseline and one year
Pain Score
Pain score on a zero to ten scale reflects "yesterday's worst pain".
Time frame: Up to one year
Number of ED Visits for SCD Pain
Measure of morbidity and healthcare utilization
Time frame: One year
Number Hospitalizations for SCD Pain
Measure of morbidity and healthcare utilization
Time frame: One year
Number of Observation Unit Admission for SCD Pain
Measure of morbidity and healthcare utilization
Time frame: One year
Number of Overnight Stays for SCD Pain
Measure of morbidity and healthcare utilization
Time frame: One year
Number of Outpatient Infusion Visits for SCD Pain
Measure of morbidity and healthcare utilization
Time frame: One year
Number of Pneumonia Episodes
Measure of morbidity and healthcare utilization
Time frame: One year
Number of ICU Admissions
Measure of morbidity and healthcare utilization
Time frame: One year
Number of Deaths
Measure of disease severity
Time frame: One year
O-Link Inflammation Panel Serum
Change in O-Link Inflammation Panel Serum at one year compared to baseline. A 92 analyte panel of key molecules involved in inflammation
Time frame: Baseline and one year
O-Link Inflammation Panel Sputum
Change in O-Link Inflammation Panel Sputum at one year compared to baseline. Inflammation panel performed on sputum supernatant will be a measure of pulmonary inflammatory signatures
Time frame: Baseline and one year
Multiplex Cytokine Panel Serum
Change in Multiplex Cytokine Panel Serum at one year compared to baseline. Key inflammatory mediators including interleukins, selectins, interferon and TNF.
Time frame: Baseline and one year
Sputum frequency of activated monocytes CyTOF
Change in Sputum frequency of activated monocytes CyTOF at one year compared to baseline. Measure of pulmonary inflammation
Time frame: Baseline and one year
Sputum Frequency of Aged Neutrophils CyTOF
Change in Sputum Frequency of Aged Neutrophils CyTOF at one year compared to baseline. Measure of pulmonary inflammation
Time frame: Baseline and one year
Sputum Immune Cell Subpopulations CyTOF
Change in Sputum Immune Cell Subpopulations CyTOF at one year compared to baseline. Frequencies of all immune subpopulations will be calculated to identify pulmonary inflammation signatures.
Time frame: Baseline and one year
Sputum Immune Cell Subpopulations CyTOF
Change in Sputum Immune Cell Subpopulations CyTOF at one year compared to baseline. Measure of pulmonary inflammation
Time frame: Baseline and one year
Whole Blood Frequency of Aged Neutrophils CyTOF
Change in Whole Blood Frequency of Aged Neutrophils CyTOF at one year compared to baseline. Measure of pulmonary inflammation
Time frame: Baseline and one year
Whole Blood Immune Cell Subpopulations CyTOF
Change in Whole Blood Immune Cell Subpopulations CyTOF at one year compared to baseline. Frequencies of all immune subpopulations will be calculated to identify pulmonary inflammation signatures.
Time frame: Baseline and one year
6-Minute Walk Test
Change in 6-Minute Walk Test at one year compared to baseline. The distance covered over a time of 6 minutes. Measure of cardiopulmonary exercise reserve.
Time frame: Baseline and one year