- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03758950
Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2 (IMPROVE2)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
-
New York, New York, United States, 10025
- Mount Sinai St Luke's
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participants age 18 and older with severe SCD phenotypes (Hb SS and Sβthalassemia0):
- Do not have asthma (see exclusion criteria)
- Not currently having a painful crisis (as defined by validated pain diary questions)
- Do not have acute respiratory symptoms
- Report of recent ECW (answers "Yes" to any question in Box 1)
- Participant is already medically optimized (i.e. already on maximum dose hydroxyurea unless contraindicated and not undergoing medication titration).
Exclusion Criteria:
- Participant screens positive for possible undiagnosed asthma (Box 2)
- Pregnant or planning to become pregnant
- > 15 ED visits for SCD pain over the previous 12 months (due to concern for multi-factorial pain that may be less responsive to SCD therapies)
- Have been discharged from the hospital within the previous 7 days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Once daily inhaled placebo
|
Once daily inhaled placebo for 48 weeks
|
Active Comparator: Mometasone
Inhaled Mometasone Furoate 220 mcg DPI
|
Inhaled Mometasone for 48 weeks (with 4-week washout at study completion)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Soluble Vascular Cell Adhesion Molecule (sVCAM) level
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reticulocyte Count level
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
Plasma Free Hemoglobin level
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
LDH level
Time Frame: Baseline and one year
|
Change in LDH level at one year compared to baseline.
LDH is a marker of hemolysis
|
Baseline and one year
|
Bilirubin (Direct and Indirect) level
Time Frame: Baseline and one year
|
Change in Bilirubin level at one year compared to baseline.
Bilirubin measure of hemolysis
|
Baseline and one year
|
Hemoglobin level
Time Frame: Baseline and one year
|
Change in Hemoglobin level at one year compared to baseline.
Hemoglobin is a clinical lab test
|
Baseline and one year
|
Leukocyte Count level
Time Frame: Baseline and one year
|
Change in Leukocyte level at one year compared to baseline.
Leukocyte is a clinical lab test
|
Baseline and one year
|
Platelet Count level
Time Frame: Baseline and one year
|
Change in Platelet count level at one year compared to baseline.
Platelet count is a clinical lab test
|
Baseline and one year
|
Exhaled Nitric Oxide
Time Frame: Baseline and one year
|
Change in eNO level at one year as compared to baseline.
Nitric oxide is a marker of eosinophilic pulmonary inflammation
|
Baseline and one year
|
Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) survey
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
Medication Adherence Self-Report Scale for Asthma (MARS-A)
Time Frame: At one year
|
MARS-A is a 10-item, self-reported measure of adherence
|
At one year
|
Brain Natriuretic Peptide
Time Frame: Baseline and one year
|
Change in brain natriuretic peptide at one year compared to baseline.
Brain natriuretic peptide is a measure of atrial stretch.
|
Baseline and one year
|
Spirometry
Time Frame: Baseline and one year
|
Change in spirometry at one year compared to baseline.
Spirometry is the measure of airflow and lung function.
|
Baseline and one year
|
Pain Score
Time Frame: Up to one year
|
Pain score on a zero to ten scale reflects "yesterday's worst pain".
|
Up to one year
|
Number of ED Visits for SCD Pain
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number Hospitalizations for SCD Pain
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of Observation Unit Admission for SCD Pain
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of Overnight Stays for SCD Pain
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of Outpatient Infusion Visits for SCD Pain
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of Pneumonia Episodes
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of ICU Admissions
Time Frame: One year
|
Measure of morbidity and healthcare utilization
|
One year
|
Number of Deaths
Time Frame: One year
|
Measure of disease severity
|
One year
|
O-Link Inflammation Panel Serum
Time Frame: Baseline and one year
|
Change in O-Link Inflammation Panel Serum at one year compared to baseline.
A 92 analyte panel of key molecules involved in inflammation
|
Baseline and one year
|
O-Link Inflammation Panel Sputum
Time Frame: Baseline and one year
|
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
|
Baseline and one year
|
Multiplex Cytokine Panel Serum
Time Frame: Baseline and one year
|
Change in Multiplex Cytokine Panel Serum at one year compared to baseline.
Key inflammatory mediators including interleukins, selectins, interferon and TNF.
|
Baseline and one year
|
Sputum frequency of activated monocytes CyTOF
Time Frame: Baseline and one year
|
Change in Sputum frequency of activated monocytes CyTOF at one year compared to baseline.
Measure of pulmonary inflammation
|
Baseline and one year
|
Sputum Frequency of Aged Neutrophils CyTOF
Time Frame: Baseline and one year
|
Change in Sputum Frequency of Aged Neutrophils CyTOF at one year compared to baseline.
Measure of pulmonary inflammation
|
Baseline and one year
|
Sputum Immune Cell Subpopulations CyTOF
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
Sputum Immune Cell Subpopulations CyTOF
Time Frame: Baseline and one year
|
Change in Sputum Immune Cell Subpopulations CyTOF at one year compared to baseline.
Measure of pulmonary inflammation
|
Baseline and one year
|
Whole Blood Frequency of Aged Neutrophils CyTOF
Time Frame: Baseline and one year
|
Change in Whole Blood Frequency of Aged Neutrophils CyTOF at one year compared to baseline.
Measure of pulmonary inflammation
|
Baseline and one year
|
Whole Blood Immune Cell Subpopulations CyTOF
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
6-Minute Walk Test
Time Frame: Baseline and one year
|
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.
|
Baseline and one year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Glassberg, MD, Icahn School of Medicine at Mount Sinai
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GCO 17-1936
- R01HL142671 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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