Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Pain Crisis, Painful Crisis, Sickle Pain
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.
Interventions
DRUGMometasone Furoate
inhaled cortico-steroid (ICS) with a dosage of 220mcg once daily for 16 weeks
DRUGPlacebo
placebo training inhaler with the same instructions as the experimental group.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Jeffrey Glassberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Reticulocytes Count | baseline and 8 weeks | Mean change in reticulocytes count - the number of new red blood cells. |
| Change in FEV1/FVC | baseline and 8 weeks | Mean change in FEV1/FVC at 8 weeks compared to baseline |
| 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 |
| 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 |
| 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 |
| 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. |
| 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. |
| Asthma Control Test | 8 weeks | Asthma control test, total score from 0-25, with higher score indicating more symptoms |
| 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in February 2014, with first enrollment in March 2014, and last enrollment in October 2016
Participants by arm
| Arm | Count |
|---|---|
| Mometasone Furoate 1 puff daily (220mcg) for 16 weeks | 35 |
| Placebo 1 puff daily for 16 weeks. Training inhaler that does not contain any medication (placebo) | 17 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Mometasone Furoate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 30 years STANDARD_DEVIATION 8.56 | 36 years STANDARD_DEVIATION 9.81 | 32 years STANDARD_DEVIATION 9.28 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Male | 17 Participants | 11 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 17 |
| other Total, other adverse events | 15 / 35 | 5 / 17 |
| serious Total, serious adverse events | 0 / 35 | 0 / 17 |
Outcome results
Primary
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.
Time frame: at 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mometasone Furoate | Number of Participants Who Completed Follow up | 35 Participants |
| Placebo | Number of Participants Who Completed Follow up | 17 Participants |
Secondary
Admissions or Visits to the Hospital
Number of times participant visited the Emergency Department (ED) or was admitted to the hospital
Time frame: baseline through 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mometasone Furoate | Admissions or Visits to the Hospital | Admissions | 0.37 Events | Standard Deviation 0.77 |
| Mometasone Furoate | Admissions or Visits to the Hospital | Observation admits | 0.37 Events | Standard Deviation 0.77 |
| Mometasone Furoate | Admissions or Visits to the Hospital | ED visits | 0.97 Events | Standard Deviation 1.52 |
| Placebo | Admissions or Visits to the Hospital | Admissions | 0.47 Events | Standard Deviation 1.23 |
| Placebo | Admissions or Visits to the Hospital | ED visits | 1.12 Events | Standard Deviation 1.87 |
| Placebo | Admissions or Visits to the Hospital | Observation admits | 0.59 Events | Standard Deviation 1.18 |
Secondary
Asthma Control Test
Asthma control test, total score from 0-25, with higher score indicating more symptoms
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Asthma Control Test | 17.7 score on a scale | Standard Deviation 2.25 |
| Placebo | Asthma Control Test | 17.1 score on a scale | Standard Deviation 1.78 |
Secondary
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.
Time frame: baseline and week 20
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Change in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) | 2.8 score on a scale | Standard Deviation 22.7 |
| Placebo | Change in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) | 6.9 score on a scale | Standard Deviation 24 |
Secondary
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.
Time frame: Before ICS therapy begins and at 8 weeks post enrollment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mometasone Furoate | Change in Exhaled Nitric Oxide (eNO) | 0.63 ppb |
| Placebo | Change in Exhaled Nitric Oxide (eNO) | 2.71 ppb |
Secondary
Change in FEV1/FVC
Mean change in FEV1/FVC at 8 weeks compared to baseline
Time frame: baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Change in FEV1/FVC | -0.71 ratio | Standard Deviation 3.42 |
| Placebo | Change in FEV1/FVC | -1.41 ratio | Standard Deviation 3.39 |
Secondary
Change in Reticulocytes Count
Mean change in reticulocytes count - the number of new red blood cells.
Time frame: baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Change in Reticulocytes Count | -0.15 10^3 cells/μL | Standard Deviation 0.39 |
| Placebo | Change in Reticulocytes Count | 0.07 10^3 cells/μL | Standard Deviation 0.52 |
Secondary
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.
Time frame: Before ICS therapy begins and at 8 weeks post enrollment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Change in Soluble Vascular Cell Adhesion Molecule (sVCAM) Level | -182.47 ng/mL | Standard Deviation 785.21 |
| Placebo | Change in Soluble Vascular Cell Adhesion Molecule (sVCAM) Level | 170.25 ng/mL | Standard Deviation 182.39 |
Secondary
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
Time frame: baseline and 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | Change in the Numerical Rating Scale (NRS) for Pain | 2.09 score on a scale | Standard Deviation 2.55 |
| Placebo | Change in the Numerical Rating Scale (NRS) for Pain | 2.82 score on a scale | Standard Deviation 2.21 |
Secondary
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
Time frame: 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mometasone Furoate | The Medication Adherence Report Scale | 17.7 score on a scale | Standard Deviation 2.25 |
| Placebo | The Medication Adherence Report Scale | 17.1 score on a scale | Standard Deviation 1.78 |