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

• ClinicalTrials.gov Identifier: NCT02061202
• Recruitment Status: Completed
• First Posted: February 12, 2014
• Results First Posted: March 11, 2019
• Last Update Posted: March 11, 2019
• Sponsor: Jeffrey Glassberg
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Disease	Drug: Mometasone Furoate; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Inhaled Mometasone to Promote Reduction in Vasoocclusive Events
• Study Start Date: March 2014
• Actual Primary Completion Date: November 2017
• Actual Study Completion Date: November 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Completed Follow up [ Time Frame: at 2 years ]
   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.

Secondary Outcome Measures :

1. Change in Exhaled Nitric Oxide (eNO) [ Time Frame: Before ICS therapy begins and at 8 weeks post enrollment ]
   Change in effects of inhaled corticosteroids (ICS) as measured by exhaled nitric oxide levels, which is the primary marker of pulmonary inflammation.
2. Change in Soluble Vascular Cell Adhesion Molecule (sVCAM) Level [ Time Frame: Before ICS therapy begins and at 8 weeks post enrollment ]
   Mean Change in effects of inhaled corticosteroids vascular injury, assessed by biomarker sVCAM as a surrogate for vascular injury.
3. Change in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) [ Time Frame: baseline and week 20 ]
   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.
4. The Medication Adherence Report Scale [ Time Frame: 20 weeks ]
   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
5. Change in the Numerical Rating Scale (NRS) for Pain [ Time Frame: baseline and 20 weeks ]
   Mean change in patient reported pain NRS score, full scale range 0- 10, higher score indicate more pain
6. Asthma Control Test [ Time Frame: 8 weeks ]
   Asthma control test, total score from 0-25, with higher score indicating more symptoms
7. Admissions or Visits to the Hospital [ Time Frame: baseline through 8 weeks ]
   Number of times participant visited the Emergency Department (ED) or was admitted to the hospital
8. Change in Reticulocytes Count [ Time Frame: baseline and 8 weeks ]
   Mean change in reticulocytes count - the number of new red blood cells.
9. Change in FEV1/FVC [ Time Frame: baseline and 8 weeks ]
   Mean change in FEV1/FVC at 8 weeks compared to baseline

Eligibility Criteria

• Ages Eligible for Study: 15 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Sponsors and Collaborators

Jeffrey Glassberg

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jeffrey Glassberg, MD, MA; Icahn School of Medicine at Mount Sinai

  Study Documents (Full-Text)

Documents provided by Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai:

Study Protocol and Statistical Analysis Plan  [PDF] November 18, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Langer AL, Leader A, Kim-Schulze S, Ginzburg Y, Merad M, Glassberg J. Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial. Ann Hematol. 2019 Apr;98(4):841-849. doi: 10.1007/s00277-019-03635-9. Epub 2019 Feb 20.

Glassberg J, Minnitti C, Cromwell C, Cytryn L, Kraus T, Skloot GS, Connor JT, Rahman AH, Meurer WJ. Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple-blind, randomized trial. Am J Hematol. 2017 Jul;92(7):622-631. doi: 10.1002/ajh.24742. Epub 2017 Jun 5.

• Responsible Party: Jeffrey Glassberg, Assistant Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02061202
• Other Study ID Numbers: GCO 12-1565; K23HL119351 ( U.S. NIH Grant/Contract )
• First Posted: February 12, 2014
• Results First Posted: March 11, 2019
• Last Update Posted: March 11, 2019
• Last Verified: March 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeffrey Glassberg, Icahn School of Medicine at Mount Sinai:

Sickle Cell Disease; Pain Crisis; Painful Crisis; Sickle Pain

Additional relevant MeSH terms:

Anemia, Sickle Cell; Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Mometasone Furoate; Anti-Inflammatory Agents; Dermatologic Agents; Anti-Allergic Agents