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

• Sponsor: Jeffrey Glassberg (Other)
• Overall Status: Completed
• CT.gov ID: NCT02061202
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 44.1
• Patients Per Site Per Month: 1.2

Study Details

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
• 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: Mar 1, 2014
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 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 [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) [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 [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) [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 [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 [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 [8 weeks]

   Asthma control test, total score from 0-25, with higher score indicating more symptoms

7. Admissions or Visits to the Hospital [baseline through 8 weeks]

   Number of times participant visited the Emergency Department (ED) or was admitted to the hospital

8. Change in Reticulocytes Count [baseline and 8 weeks]

   Mean change in reticulocytes count - the number of new red blood cells.

9. Change in FEV1/FVC [baseline and 8 weeks]

   Mean change in FEV1/FVC at 8 weeks compared to baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Nov 18, 2015

More Information

Publications

None provided.

• 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
• First Posted: Feb 12, 2014
• Last Update Posted: Mar 11, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jeffrey Glassberg, Assistant Professor, Icahn School of Medicine at Mount Sinai: Sickle Cell Disease; Pain Crisis; Painful Crisis; Sickle Pain
• Additional relevant MeSH terms: Anemia, Sickle Cell; Mometasone Furoate

Study Results

Participant Flow

Recruitment Details	Recruitment began in February 2014, with first enrollment in March 2014, and last enrollment in October 2016

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Period Title: Overall Study
STARTED	36	18
COMPLETED	35	17
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Mometasone Furoate	Placebo	Total
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)	Total of all reporting groups
Overall Participants	35	17	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30 (8.56)	36 (9.81)	32 (9.28)
Sex: Female, Male (Count of Participants)
Female	18 51.4%	6 35.3%	24 46.2%
Male	17 48.6%	11 64.7%	28 53.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Completed Follow up
Description	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.
Time Frame	at 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	36	18
Count of Participants [Participants]	35 100%	17 100%

2. Secondary Outcome

Title	Change in Exhaled Nitric Oxide (eNO)
Description	Change in effects of inhaled corticosteroids (ICS) as measured by exhaled nitric oxide levels, which is the primary marker of pulmonary inflammation.
Time Frame	Before ICS therapy begins and at 8 weeks post enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (95% Confidence Interval) [ppb]	0.63	2.71

3. Secondary Outcome

Title	Change in Soluble Vascular Cell Adhesion Molecule (sVCAM) Level
Description	Mean Change in effects of inhaled corticosteroids vascular injury, assessed by biomarker sVCAM as a surrogate for vascular injury.
Time Frame	Before ICS therapy begins and at 8 weeks post enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [ng/mL]	-182.47 (785.21)	170.25 (182.39)

4. Secondary Outcome

Title	Change in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me)
Description	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.
Time Frame	baseline and week 20

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [score on a scale]	2.8 (22.7)	6.9 (24.0)

5. Secondary Outcome

Title	The Medication Adherence Report Scale
Description	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
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [score on a scale]	17.7 (2.25)	17.1 (1.78)

6. Secondary Outcome

Title	Change in the Numerical Rating Scale (NRS) for Pain
Description	Mean change in patient reported pain NRS score, full scale range 0- 10, higher score indicate more pain
Time Frame	baseline and 20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [score on a scale]	2.09 (2.55)	2.82 (2.21)

7. Secondary Outcome

Title	Asthma Control Test
Description	Asthma control test, total score from 0-25, with higher score indicating more symptoms
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [score on a scale]	17.7 (2.25)	17.1 (1.78)

8. Secondary Outcome

Title	Admissions or Visits to the Hospital
Description	Number of times participant visited the Emergency Department (ED) or was admitted to the hospital
Time Frame	baseline through 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
ED visits	0.97 (1.52)	1.12 (1.87)
Observation admits	0.37 (0.77)	0.59 (1.18)
Admissions	0.37 (0.77)	0.47 (1.23)

9. Secondary Outcome

Title	Change in Reticulocytes Count
Description	Mean change in reticulocytes count - the number of new red blood cells.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [10^3 cells/μL]	-0.15 (0.39)	0.07 (0.52)

10. Secondary Outcome

Title	Change in FEV1/FVC
Description	Mean change in FEV1/FVC at 8 weeks compared to baseline
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mometasone Furoate	Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks	1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
Measure Participants	35	17
Mean (Standard Deviation) [ratio]	-0.71 (3.42)	-1.41 (3.39)

Adverse Events

Time Frame	2 years
Arm/Group Title	Mometasone Furoate		Placebo
Arm/Group Description	1 puff daily (220mcg) for 16 weeks		1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo)
All Cause Mortality
	Mometasone Furoate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/17 (0%)
Serious Adverse Events
	Mometasone Furoate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Mometasone Furoate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/35 (42.9%)		5/17 (29.4%)
Respiratory, thoracic and mediastinal disorders
Hoarseness of voice	15/35 (42.9%)		4/17 (23.5%)
Thrush	2/35 (5.7%)		0/17 (0%)
Sore Throat	15/35 (42.9%)		5/17 (29.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.