Sickle Cell DiseasePhase 2IMPROVE2NCT03758950
Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
A Phase 2 study testing Mometasone in people with Sickle Cell Disease, run by Jeffrey Glassberg at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Mometasone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Nov 2018to 31 May 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mount Sinai St Luke's
New York, New York, 10025
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Placebo, Mometasone
- Keywords
- Sickle Cell, Inhaled Steroids
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Once daily inhaled placebo for 48 weeks
MometasoneDrug
Also called Inhaled Mometasone
Inhaled Mometasone for 48 weeks (with 4-week washout at study completion)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Once daily inhaled placebo Receives: Drug: Placebo |
| Mometasone | Active comparator | Inhaled Mometasone Furoate 220 mcg DPI Receives: Drug: Mometasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and one year
Secondary outcomes (31)
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.
Measured: 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.
Measured: Baseline and one year
LDH level
Change in LDH level at one year compared to baseline. LDH is a marker of hemolysis
Measured: Baseline and one year
Bilirubin (Direct and Indirect) level
Change in Bilirubin level at one year compared to baseline. Bilirubin measure of hemolysis
Measured: Baseline and one year
Hemoglobin level
Change in Hemoglobin level at one year compared to baseline. Hemoglobin is a clinical lab test
Measured: Baseline and one year
Leukocyte Count level
Change in Leukocyte level at one year compared to baseline. Leukocyte is a clinical lab test
Measured: 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
Measured: 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
Measured: 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.
Measured: Baseline and one year
Medication Adherence Self-Report Scale for Asthma (MARS-A)
MARS-A is a 10-item, self-reported measure of adherence
Measured: 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.
Measured: Baseline and one year
Spirometry
Change in spirometry at one year compared to baseline. Spirometry is the measure of airflow and lung function.
Measured: Baseline and one year
Pain Score
Pain score on a zero to ten scale reflects "yesterday's worst pain".
Measured: Up to one year
Number of ED Visits for SCD Pain
Measure of morbidity and healthcare utilization
Measured: One year
Number Hospitalizations for SCD Pain
Measure of morbidity and healthcare utilization
Measured: One year
Number of Observation Unit Admission for SCD Pain
Measure of morbidity and healthcare utilization
Measured: One year
Number of Overnight Stays for SCD Pain
Measure of morbidity and healthcare utilization
Measured: One year
Number of Outpatient Infusion Visits for SCD Pain
Measure of morbidity and healthcare utilization
Measured: One year
Number of Pneumonia Episodes
Measure of morbidity and healthcare utilization
Measured: One year
Number of ICU Admissions
Measure of morbidity and healthcare utilization
Measured: One year
Number of Deaths
Measure of disease severity
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Baseline and one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2018
- Study start29 Nov 2018
- Primary completion31 May 2023
- Study completion31 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Glassberg
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai
- Investigators
- Jeffrey Glassberg, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03758950
- Sponsor's protocol ID
- GCO 17-1936
- Other IDs
- R01HL142671
- Acronym
- IMPROVE2
- Status last verified
- Jun 2023
- First submitted
- 28 Nov 2018
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
- ClinicalTrials.gov ID
- NCT03758950
- Acronym / sponsor ID
- IMPROVE2 / GCO 17-1936
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell, Inhaled Steroids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Jeffrey GlassbergUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 29 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboOnce daily inhaled placebo |
| Mometasone | Active comparator | Drug: MometasoneInhaled Mometasone Furoate 220 mcg DPI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboOnce daily inhaled placebo for 48 weeks | Drug | Placebo |
| MometasoneAlso: Inhaled MometasoneInhaled Mometasone for 48 weeks (with 4-week washout at study completion) | Drug | Mometasone |
Primary outcome
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.
31 secondary outcomes
Reticulocyte Count level
Time frame: Baseline and one year
Plasma Free Hemoglobin level
Time frame: Baseline and one year
LDH level
Time frame: Baseline and one year
Bilirubin (Direct and Indirect) level
Time frame: Baseline and one year
Hemoglobin level
Time frame: Baseline and one year
Leukocyte Count level
Time frame: Baseline and one year
Platelet Count level
Time frame: Baseline and one year
Exhaled Nitric Oxide
Time frame: Baseline and one year
Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) survey
Time frame: Baseline and one year
Medication Adherence Self-Report Scale for Asthma (MARS-A)
Time frame: At one year
Brain Natriuretic Peptide
Time frame: Baseline and one year
Spirometry
Time frame: Baseline and one year
Pain Score
Time frame: Up to one year
Number of ED Visits for SCD Pain
Time frame: One year
Number Hospitalizations for SCD Pain
Time frame: One year
Number of Observation Unit Admission for SCD Pain
Time frame: One year
Number of Overnight Stays for SCD Pain
Time frame: One year
Number of Outpatient Infusion Visits for SCD Pain
Time frame: One year
Number of Pneumonia Episodes
Time frame: One year
Number of ICU Admissions
Time frame: One year
Number of Deaths
Time frame: One year
O-Link Inflammation Panel Serum
Time frame: Baseline and one year
O-Link Inflammation Panel Sputum
Time frame: Baseline and one year
Multiplex Cytokine Panel Serum
Time frame: Baseline and one year
Sputum frequency of activated monocytes CyTOF
Time frame: Baseline and one year
Sputum Frequency of Aged Neutrophils CyTOF
Time frame: Baseline and one year
Sputum Immune Cell Subpopulations CyTOF
Time frame: Baseline and one year
Sputum Immune Cell Subpopulations CyTOF
Time frame: Baseline and one year
Whole Blood Frequency of Aged Neutrophils CyTOF
Time frame: Baseline and one year
Whole Blood Immune Cell Subpopulations CyTOF
Time frame: Baseline and one year
6-Minute Walk Test
Time frame: Baseline and one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Glassberg, MD principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mometasone in people with Sickle Cell Disease, run by Jeffrey Glassberg at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Soluble Vascular Cell Adhesion Molecule (sVCAM) level (time frame: Baseline and one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023; AzTrials last refreshed its copy on 7 Nov 2026.