Inhaled Mometasone to Reduce Painful Episodes in Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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The proposed research is designed to test the global hypothesis that inhaled corticosteroids (ICS), a therapy developed to treat asthma, will prevent vasoocclusive painful episodes in adults with Sickle Cell Disease (SCD) who wheeze, but do not meet criteria for a diagnosis of asthma. The specific aims of this proposal are 1) Conduct a feasibility study - a randomized controlled trial of ICS for adults with SCD who do not meet criteria for a diagnosis of asthma but report recurrent cough or wheezing, 2) Measure the effects of ICS on biological correlates of pulmonary inflammation (as determined by exhaled nitric oxide) and vascular injury (as determined by sVCAM) in SCD, and 3) Compare properties of traditional and Bayesian adaptive clinical trial design for therapeutic trials in SCD in preparation for designing a definitive trial of ICS. These aims have the potential to 1) change the standard of care for individuals with SCD and recurrent cough or wheeze, 2) provide insight into the pathogenesis of non-asthmatic wheezing in SCD and its response to treatment, 3) explore the suitability of innovative clinical trial designs to overcome the challenges that have hindered therapeutic innovation for SCD.

Official Title
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Inhaled Mometasone to Promote Reduction in Vasoocclusive Events

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Mometasone Furoate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 15 or older Sever SCD phenotypes (Hb SS and Sβthalassemia0) A positive response to cough/wheeze questions Exclusion Criteria: Patient carries a physician diagnosis of asthma Patient is prescribed asthma medications Patient is currently having a painful crisis (as defined by validated pain diary questions) Patient has acute respiratory symptoms Known hypersensitivity to milk proteins Meets criteria for our operational diagnosis of asthma More than 15 ED visits for pain over the preceding 12 months Admitted or discharged from the hospital for SCD pain within the last 7 days

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mometasone Furoate<br>1 puff daily (220mcg) for 16 weeks | Drug: Mometasone Furoate<br>* inhaled cortico-steroid (ICS) with a dosage of 220mcg once daily for 16 weeks<br>|
| Placebo Comparator: Placebo<br>1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo). | Drug: Placebo<br>* placebo training inhaler with the same instructions as the experimental group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Completed Follow up | Feasibility is determined by calculating the proportion of randomized participants who complete follow up and a minimum of 30 pain diaries with good adherence to the study medication vs. the number enrolled. | at 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Exhaled Nitric Oxide (eNO) | Change in effects of inhaled corticosteroids (ICS) as measured by exhaled nitric oxide levels, which is the primary marker of pulmonary inflammation. | Before ICS therapy begins and at 8 weeks post enrollment | 
| Change in Soluble Vascular Cell Adhesion Molecule (sVCAM) Level | Mean Change in effects of inhaled corticosteroids vascular injury, assessed by biomarker sVCAM as a surrogate for vascular injury. | Before ICS therapy begins and at 8 weeks post enrollment | 
| Change in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) | Mean changes in ASCQ-Me (NHLBI developed a patient-reported Sickle Cell Disease (SCD) quality of life measurement tool) pain impact, at week 20 as compared to baseline. A reduction change on a 100-point scale indicated improved quality of life. ASCQ-Me uses a T-score metric (0-100) in which 50 is the mean of the reference population and 10 is the standard deviation (SD) of that population. | baseline and week 20 | 
| The Medication Adherence Report Scale | The medication adherence report scale for asthma is a 10 question tool scored between 0 and 5, with full scale from 0 to 25, with higher scores indicating greater adherence | 20 weeks | 
| Change in the Numerical Rating Scale (NRS) for Pain | Mean change in patient reported pain NRS score, full scale range 0- 10, higher score indicate more pain | baseline and 20 weeks | 
| Asthma Control Test | Asthma control test, total score from 0-25, with higher score indicating more symptoms | 8 weeks | 
| Admissions or Visits to the Hospital | Number of times participant visited the Emergency Department (ED) or was admitted to the hospital | baseline through 8 weeks | 
| Change in Reticulocytes Count | Mean change in reticulocytes count - the number of new red blood cells. | baseline and 8 weeks | 
| Change in FEV1/FVC | Mean change in FEV1/FVC at 8 weeks compared to baseline | baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Pain Crisis, Painful Crisis, Sickle Pain