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Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2 (IMPROVE2)

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ClinicalTrials.gov Identifier: NCT03758950
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE November 28, 2018
First Posted Date  ICMJE November 29, 2018
Last Update Posted Date December 17, 2018
Actual Study Start Date  ICMJE November 29, 2018
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03758950 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • 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.
  • 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.
  • LDH level [ Time Frame: Baseline and one year ]
    Change in LDH level at one year compared to baseline. LDH is a marker of hemolysis
  • 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
  • Hemoglobin level [ Time Frame: Baseline and one year ]
    Change in Hemoglobin level at one year compared to baseline. Hemoglobin is a clinical lab test
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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.
  • 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.
  • Pain Score [ Time Frame: Up to one year ]
    Pain score on a zero to ten scale reflects "yesterday's worst pain".
  • Number of ED Visits for SCD Pain [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number Hospitalizations for SCD Pain [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of Observation Unit Admission for SCD Pain [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of Overnight Stays for SCD Pain [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of Outpatient Infusion Visits for SCD Pain [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of Pneumonia Episodes [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of ICU Admissions [ Time Frame: One year ]
    Measure of morbidity and healthcare utilization
  • Number of Deaths [ Time Frame: One year ]
    Measure of disease severity
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
Official Title  ICMJE Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple blind
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: Placebo
    Once daily inhaled placebo for 48 weeks
  • Drug: Mometasone
    Inhaled Mometasone for 48 weeks (with 4-week washout at study completion)
    Other Name: Inhaled Mometasone
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Once daily inhaled placebo
    Intervention: Drug: Placebo
  • Active Comparator: Mometasone
    Inhaled Mometasone Furoate 220 mcg DPI
    Intervention: Drug: Mometasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2018)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeffrey Glassberg, MD 212-241-3650 jeffrey.glassberg@mountsinai.org
Contact: Cindy Clesca, BA 212-824-8057 cindy.clesca@mountsinai.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03758950
Other Study ID Numbers  ICMJE GCO 17-1936
R01HL142671 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Jeffrey Glassberg
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Jeffrey Glassberg, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP