Clinical trial NCT03758950: Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
Official title: Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Sickle Cell
Inhaled Steroids
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-11-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Soluble Vascular Cell Adhesion Molecule (sVCAM) level
timeFrame: Baseline and one year
Secondary outcomes:
measure: Reticulocyte Count level
timeFrame: Baseline and one year
measure: Plasma Free Hemoglobin level
timeFrame: Baseline and one year
measure: LDH level
timeFrame: Baseline and one year
measure: Bilirubin (Direct and Indirect) level
timeFrame: Baseline and one year
measure: Hemoglobin level
timeFrame: Baseline and one year
measure: Leukocyte Count level
timeFrame: Baseline and one year
measure: Platelet Count level
timeFrame: Baseline and one year
measure: Exhaled Nitric Oxide
timeFrame: Baseline and one year
measure: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) survey
timeFrame: Baseline and one year
measure: Medication Adherence Self-Report Scale for Asthma (MARS-A)
timeFrame: At one year
measure: Brain Natriuretic Peptide
timeFrame: Baseline and one year
measure: Spirometry
timeFrame: Baseline and one year
measure: Pain Score
timeFrame: Up to one year
measure: Number of ED Visits for SCD Pain
timeFrame: One year
measure: Number Hospitalizations for SCD Pain
timeFrame: One year
measure: Number of Observation Unit Admission for SCD Pain
timeFrame: One year
measure: Number of Overnight Stays for SCD Pain
timeFrame: One year
measure: Number of Outpatient Infusion Visits for SCD Pain
timeFrame: One year
measure: Number of Pneumonia Episodes
timeFrame: One year
measure: Number of ICU Admissions
timeFrame: One year
measure: Number of Deaths
timeFrame: One year
measure: O-Link Inflammation Panel Serum
timeFrame: Baseline and one year
measure: O-Link Inflammation Panel Sputum
timeFrame: Baseline and one year
measure: Multiplex Cytokine Panel Serum
timeFrame: Baseline and one year
measure: Sputum frequency of activated monocytes CyTOF
timeFrame: Baseline and one year
measure: Sputum Frequency of Aged Neutrophils CyTOF
timeFrame: Baseline and one year
measure: Sputum Immune Cell Subpopulations CyTOF
timeFrame: Baseline and one year
measure: Sputum Immune Cell Subpopulations CyTOF
timeFrame: Baseline and one year
measure: Whole Blood Frequency of Aged Neutrophils CyTOF
timeFrame: Baseline and one year
measure: Whole Blood Immune Cell Subpopulations CyTOF
timeFrame: Baseline and one year
measure: 6-Minute Walk Test
timeFrame: Baseline and one year
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai St Luke's
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Glassberg, MD
role: PRINCIPAL_INVESTIGATOR
References: