Sickle Cell DiseaseMoP-ASCNCT01879592
Molecular Phenotyping of Asthma in Sickle Cell Disease
An observational study of Sickle Cell Disease and Asthma, run by Nemours Children's Clinic at 3 sites in United States.
Trial summary
Asthma and sickle cell disease each are serious medical problems. People with asthma have difficulty breathing, wheeze (a whistling noise when breathing), cough, produce sputum or phlegm, and have inflammation (swelling, irritation, redness) and narrowing of the bronchial tubes. Read more about this study
- Who is it for?
- Ages 6 to 20 years
- Conditions the study is for
- Sickle Cell Disease, Asthma
- How many people
- 99 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2011to 28 Feb 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Three groups of 30 children each will be studied: Group 1, children with asthma and sickle cell disease; Group 2, children with sickle cell disease but without asthma; Group 3, control group of 30 African American children with asthma but without sickle cell disease ; Group 4, healthy control group of 25 African American children with no chronic disease. All children are seen at Nemours Children's Clinics in Jacksonville FL, Orlando FL, or Wilmington DE.
Who may be able to join
- Patients are aged 6 years old up to 21 years old
- Children with sickle cell disease with the genotype SS, SC, or S β 0 thal
- African American children with asthma who do not have sickle cell disease or sickle cell disease trait.
- African American children with no chronic disease
- Physician diagnosed asthma and atopy (of any asthma severity) plus a family history of asthma 89,90
- Patients whose controller respiratory medications and maintenance medications for sickle cell disease (e.g. hydroxyurea) have been unchanged for the previous 4 weeks
Who cannot join
- Patients who are current smokers
- Patients who had an inflammatory event related to sickle cell disease (pain episode, priapism, acute chest syndrome, urgent medical visit), asthma exacerbation, or respiratory infection within 1 month prior to the blood, saliva, and urine collection.
- Patients who are receiving chronic transfusion therapy and who have received a transfusion within 90 days prior to blood, saliva, and urine collection.
- Patients who have received treatment with a leukotriene synthesis inhibitor or a leukotriene modifier[montelukast (Singulair®)] within the 2 weeks prior to blood and urine collection.
- Women who are pregnant or lactating
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Nemours Children's Clinic
Jacksonville, Florida, 32207
Nemours Children's Clinic
Orlando, Florida, 32827
Nemours Children's Clinic
Wilmington, Delaware, 19803
About this study
Asthma and sickle cell disease each are serious medical problems. People with asthma have difficulty breathing, wheeze (a whistling noise when breathing), cough, produce sputum or phlegm, and have inflammation (swelling, irritation, redness) and narrowing of the bronchial tubes.
When a person has both asthma and sickle cell disease together, more serious medical problems can occur such as having acute chest syndrome and pain episodes more often. It is sometimes hard to diagnose asthma in a person with sickle cell disease because sickle cell disease can also cause lung problems.
The purpose of this study is to see if the investigators can better understand asthma when it occurs in a person who has sickle cell disease. The investigators will do this by taking a blood, urine, and saliva sample. The blood and urine samples will be analyzed for chemicals and DNA (genes). Certain genes can cause patients to have sickle cell disease or asthma. The investigators will use the saliva sample for future studies to compare the results from the blood testing with saliva. The investigator's long-term goal is to make sure people who have asthma and sickle cell disease are getting the best asthma treatments. The investigator's hypothesis is that the analysis of the blood, urine and saliva using a method called, metabolomics, may identify a unique asthma signature in children with sickle cell disease which may lead to targeted treatments.
Read the detailed description
Asthma recently has been described as a disorder of multiple subphenotypes despite a common symptom presentation. These subphenotypes have differing molecular pathways and discovering these differences may lead to better diagnosis strategies and new treatments. Most studies investigating asthma pathways are driven by the scientist's own theories and experience and thus, are considered biased. Metabolomics, an exciting and innovative discipline, represents an unbiased, hypothesis free approach to defining a molecular phenotype of asthma.
Sickle cell disease is a common genetic disorder and there is ample evidence that asthma is a common co-morbidity with an asthma prevalence of 2% to 45% compared with 12.8% in African American children without sickle cell disease. Acute chest syndrome (ACS) contributes to the cause of death in up to 60% of deaths in sickle cell patients and there is a strong relationship between having asthma and the risk of developing ACS and an increased risk of death.
Metabolomics is the study of the entire repertoire of small molecules present in cells, tissues, organs and biological fluids that comprise the metabolome. Metabolomics measures the downstream products of protein, gene, and environmental interactions and importantly, comes closest to expressing phenotype, and provides the opportunity to explore gene by environment and gene by gene interactions. A systems biology approach using metabolomics has been advocated to better understand pulmonary disease.
Asthma in the sickle cell patient is likely to have a molecular fingerprint which can be distinguished from asthma in the non-sickle cell patient. The investigator's specific aim is to compare the urinary metabolomic profile of children with asthma and sickle cell disease to children without asthma who have sickle cell disease, and to a cohort of African American children with asthma but without sickle cell disease. The hypothesis is that children with asthma and sickle cell disease will have a unique metabolomic profile that will discriminate these patients from children with sickle cell disease who have respiratory dysfunction that is not asthma, and from children with asthma who do not have sickle cell disease.
The investigators will collect a single saliva, urine and blood specimen from children with asthma and sickle cell disease, children with sickle cell disease only, and African American children with asthma only for metabolomic analysis. A single urine sample will be collected from health African American children without any chronic diseases. Blood will be stored for a future study to compare metabolomic variability between blood and urine. The investigator's goal is to use this information to correctly identify children with asthma. These data will enhance the investigator's understanding of the mechanisms that underlie the molecular asthma phenotype in sickle cell disease, which should lead to more targeted treatment of asthma in sickle cell disease. The investigators long-term goal is to reduce the burden of asthma in the child with sickle cell disease (pain, ACS, and death) by using this innovative systems biology approach.
- Conditions
- Sickle Cell Disease, Asthma
- Keywords
- Sickle cell disease, Asthma, Metabolomics, Gene expression
- Medical subject headings
- Anemia, Sickle Cell, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Asthma + sickle cell disease | African American children affected with both sickle cell disease and asthma | |
| Sickle cell disease | African American children affected with sickle cell disease but who do not have asthma | |
| Asthma | African American children affected with asthma but without sickle cell disease | |
| Healthy control | African American children who are healthy with no chronic disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolomic Principal Component Profile
Principal component analysis of differences in the variability in the metabolomic profile of children with asthma and sickle cell disease compared with children with sickle cell disease only and a cohort of African American children with asthma only and a cohort of African American children with no chronic disease.
Measured: Day 1
Secondary outcomes (2)
Placenta Growth Factor (PlGF) plasma concentrations
Differences in PlGF plasma concentrations in children with asthma and sickle cell disease compared with children with sickle cell disease only and a cohort of African American children with asthma only.
Measured: Day 1
Messenger ribonucleic acid (mRNA) transcript levels
Differences in mRNA transcript levels of 5-lipoxygenase (ALOX5) and five-lipoxygenase activating protein (FLAP) genes in children with asthma and sickle cell disease compared with children with sickle cell disease only and a cohort of African American children with asthma only.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2013 (estimated)
- Study startJun 2011
- Primary completion28 Feb 2016
- Study completion28 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kathryn Blake, PharmD, Nemours Children's Clinic
- Investigators
- Kathryn Blake, PharmD, Principal investigator, Nemours Children's Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01879592
- Sponsor's protocol ID
- 202349
- Acronym
- MoP-ASC
- Status last verified
- Mar 2017
- First submitted
- 12 Apr 2013
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Our consent documents did not include sharing of individual participant data
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Phenotyping of Asthma in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01879592
- Acronym / sponsor ID
- MoP-ASC / 202349
- Conditions
- Sickle Cell Disease, Asthma
- Keywords
- Sickle cell disease, Asthma, Metabolomics, Gene expression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- 28 Feb 2016 (actual)
- Study completion
- 28 Feb 2016 (actual)
- First posted
- 18 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Asthma and sickle cell disease each are serious medical problems. People with asthma have difficulty breathing, wheeze (a whistling noise when breathing), cough, produce sputum or phlegm, and have inflammation (swelling, irritation, redness) and narrowing of the bronchial tubes.
When a person has both asthma and sickle cell disease together, more serious medical problems can occur such as having acute chest syndrome and pain episodes more often. It is sometimes hard to diagnose asthma in a person with sickle cell disease because sickle cell disease can also cause lung problems.
The purpose of this study is to see if the investigators can better understand asthma when it occurs in a person who has sickle cell disease. The investigators will do this by taking a blood, urine, and saliva sample. The blood and urine samples will be analyzed for chemicals and DNA (genes). Certain genes can cause patients to have sickle cell disease or asthma. The investigators will use the saliva sample for future studies to compare the results from the blood testing with saliva. The investigator's long-term goal is to make sure people who have asthma and sickle cell disease are getting the best asthma treatments. The investigator's hypothesis is that the analysis of the blood, urine and saliva using a method called, metabolomics, may identify a unique asthma signature in children with sickle cell disease which may lead to targeted treatments.
Detailed description
Asthma recently has been described as a disorder of multiple subphenotypes despite a common symptom presentation. These subphenotypes have differing molecular pathways and discovering these differences may lead to better diagnosis strategies and new treatments. Most studies investigating asthma pathways are driven by the scientist's own theories and experience and thus, are considered biased. Metabolomics, an exciting and innovative discipline, represents an unbiased, hypothesis free approach to defining a molecular phenotype of asthma.
Sickle cell disease is a common genetic disorder and there is ample evidence that asthma is a common co-morbidity with an asthma prevalence of 2% to 45% compared with 12.8% in African American children without sickle cell disease. Acute chest syndrome (ACS) contributes to the cause of death in up to 60% of deaths in sickle cell patients and there is a strong relationship between having asthma and the risk of developing ACS and an increased risk of death.
Metabolomics is the study of the entire repertoire of small molecules present in cells, tissues, organs and biological fluids that comprise the metabolome. Metabolomics measures the downstream products of protein, gene, and environmental interactions and importantly, comes closest to expressing phenotype, and provides the opportunity to explore gene by environment and gene by gene interactions. A systems biology approach using metabolomics has been advocated to better understand pulmonary disease.
Asthma in the sickle cell patient is likely to have a molecular fingerprint which can be distinguished from asthma in the non-sickle cell patient. The investigator's specific aim is to compare the urinary metabolomic profile of children with asthma and sickle cell disease to children without asthma who have sickle cell disease, and to a cohort of African American children with asthma but without sickle cell disease. The hypothesis is that children with asthma and sickle cell disease will have a unique metabolomic profile that will discriminate these patients from children with sickle cell disease who have respiratory dysfunction that is not asthma, and from children with asthma who do not have sickle cell disease.
The investigators will collect a single saliva, urine and blood specimen from children with asthma and sickle cell disease, children with sickle cell disease only, and African American children with asthma only for metabolomic analysis. A single urine sample will be collected from health African American children without any chronic diseases. Blood will be stored for a future study to compare metabolomic variability between blood and urine. The investigator's goal is to use this information to correctly identify children with asthma. These data will enhance the investigator's understanding of the mechanisms that underlie the molecular asthma phenotype in sickle cell disease, which should lead to more targeted treatment of asthma in sickle cell disease. The investigators long-term goal is to reduce the burden of asthma in the child with sickle cell disease (pain, ACS, and death) by using this innovative systems biology approach.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Asthma + sickle cell disease | – | –African American children affected with both sickle cell disease and asthma |
| Sickle cell disease | – | –African American children affected with sickle cell disease but who do not have asthma |
| Asthma | – | –African American children affected with asthma but without sickle cell disease |
| Healthy control | – | –African American children who are healthy with no chronic disease |
Who may qualify
- Ages
- 6 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Three groups of 30 children each will be studied: Group 1, children with asthma and sickle cell disease; Group 2, children with sickle cell disease but without asthma; Group 3, control group of 30 African American children with asthma but without sickle cell disease ; Group 4, healthy control group of 25 African American children with no chronic disease. All children are seen at Nemours Children's Clinics in Jacksonville FL, Orlando FL, or Wilmington DE.
Key inclusion criteria (6 listed)
- Patients are aged 6 years old up to 21 years old
- Children with sickle cell disease with the genotype SS, SC, or S β 0 thal
- African American children with asthma who do not have sickle cell disease or sickle cell disease trait.
- African American children with no chronic disease
- Physician diagnosed asthma and atopy (of any asthma severity) plus a family history of asthma 89,90
Key exclusion criteria (5 listed)
- Patients who are current smokers
- Patients who had an inflammatory event related to sickle cell disease (pain episode, priapism, acute chest syndrome, urgent medical visit), asthma exacerbation, or respiratory infection within 1 month prior to the blood, saliva, and urine collection.
- Patients who are receiving chronic transfusion therapy and who have received a transfusion within 90 days prior to blood, saliva, and urine collection.
- Patients who have received treatment with a leukotriene synthesis inhibitor or a leukotriene modifier[montelukast (Singulair®)] within the 2 weeks prior to blood and urine collection.
- Women who are pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Metabolomic Principal Component Profile
Time frame: Day 1
Principal component analysis of differences in the variability in the metabolomic profile of children with asthma and sickle cell disease compared with children with sickle cell disease only and a cohort of African American children with asthma only and a cohort of African American children with no chronic disease.
2 secondary outcomes
Placenta Growth Factor (PlGF) plasma concentrations
Time frame: Day 1
Messenger ribonucleic acid (mRNA) transcript levels
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
- Individual participant dataSharing planned: No. Our consent documents did not include sharing of individual participant data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathryn Blake, PharmD principal investigator
Nemours Children's Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease and Asthma, run by Nemours Children's Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolomic Principal Component Profile (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2017.