Chuvash PolycythemiaNCT00495638
Pulmonary Hypertension, Hypoxia and Sickle Cell Disease
An observational study of Chuvash Polycythemia and Cerebrovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 7 sites in 2 countries.
Trial summary
The study will look at the risk factors for pulmonary hypertension (high blood pressure in the lungs) in children and adolescents with sickle cell anemia (SCA) and examine the role of hypoxia (oxygen shortage) in the disease. Read more about this study
- Who is it for?
- Ages 3 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Chuvash Polycythemia, Cerebrovascular Disease, Pulmonary Hypertension
- How many people
- 29 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 28 Jun 2007to 2 Dec 2014
- 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 3 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- For PAH in children and adolescents with SCD:
- The informed consent has been signed by the participant, parent or legal guardian as appropriate.
- Age of 3 to 20 years.
- Diagnosis of sickle cell disease (electrophoretic HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore is required).
- At least three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD.
- Absence of acute infection, pain crisis, or other acute complication of SCD. (Chronic SCD complications such as stuttering priapism, stable chronic pain and leg ulcers are not reasons for exclusion.)
Show all 37Show fewer
- Self-described race is African American.
- Absence of diagnosis of SCD as defined above and subsequent electrophoretic or HPLC documentation.
- Absence of acute infection, injury, surgery or asthmatic episode.
- The informed consent has been signed by the participant, parent or legal guardian as appropriate.
- Age of 3 years or greater.
- Absence of acute infection, pain crisis, cerebral vascular accident, thrombosis or other acute complication.
- Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sbeta thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine.
- At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV of 2.5 m/sec or greater.
- Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine.
- At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV less than 2.5 m/sec.
- Matched by age (plus or minus 2 years), sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study.
- Absence of diagnosis of SCD as defined above and subsequent electrophoretic documentation.
- Absence of diagnosis of CP and subsequent documentation of VHL 598 wildtype.
- At least three weeks has elapsed since hospitalization for illness or surgery.
- Matched by age (plus or minus 2 years) and sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study.
- Absence of diagnosis of PAH, anemia, or polycythemia.
- The informed consent has been signed by the participant, parent or legal guardian as appropriate.
- Age of 3 years or greater.
- Absence of acute infection, pain crisis, cerebral vascular accident, thrombosis or other acute complication.
- Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine.
- At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV of 2.5 m/sec or greater.
- Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine.
- At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV less than 2.5 m/sec
- Matched by age (plus or minus 2 years), sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study.
- Inclusion criteria for screening for population prevalence of polymorphisms:
- Absence of diagnosis of SCD, CP or PAH.
- Self-described African-American or Chuvash ethnicity.
Who cannot join
- Age of less than 3 years or 21 years or more at time of enrollment.
- Presence of acute infection, pain crisis, injury, surgery, asthmatic episode or other acute complication.
- Hemoglobin A only phenotype, hemoglobin S trait or hemoglobin C trait.
- Less than three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD.
- Self-described ethnicity other than African American.
- Diagnosis of SCD or electrophoretic or HPLC documentation of major sickling phenotype as described above.
Show all 32Show fewer
- Angiogenic and vasomotor responses mediated by HIF-regulated pathways in patients with SCD and CP with and without PAH.
- Age of less than 3 years.
- Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease.
- Presence of acute infection, injury, surgery, asthmatic episode, pain crisis, cerebral vascular accident, thrombosis or other acute complication.
- Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype.
- Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV less than 2.5 m/sec.
- Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype.
- Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV greater than or equal to 2.5 m/sec.
- Diagnosis of SCD or electrophoretic or HPLC evidence of major sickling phenotype as described above OR diagnosis of CP or for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine homozygosity.
- ECHO-determined TRV greater than or equal to 2.5 m/sec.
- High throughput microarray and genotyping technologies to identify candidate gene polymorphisms involved in pathologic responses to hypoxia in SCD and CP patients with PAH.
- Age of less than 3 years.
- Presence of acute infection, injury, surgery, asthmatic episode, pain crisis, cerebral vascular accident, thrombosis or other acute complication.
- Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype.
- Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease.
- Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV less than 2.5 m/sec.
- Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype.
- Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease.
- Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication).
- ECHO-determined TRV greater than or equal to 2.5 m/sec.
- Exclusion criteria for screening for population prevalence of polymorphisms
- Diagnosis of SCD, CP or PAH.
- Self-described ethnicity other than African-American or Chuvash.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
University of Michigan
Ann Arbor, Michigan, 48109-0624
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
University of Chicago
Chicago, Illinois, 60637
Baylor College of Medicine
Houston, Texas, 77030
Howard University Hospital
Washington D.C., District of Columbia, 20060
Childrens National Medical Center
Washington D.C., District of Columbia
About this study
Official title: Pulmonary Hypertension and the Hypoxic Response in SCD
The study will look at the risk factors for pulmonary hypertension (high blood pressure in the lungs) in children and adolescents with sickle cell anemia (SCA) and examine the role of hypoxia (oxygen shortage) in the disease. In patients with SCA, red blood cells become sickle-shaped and tend to form clumps that get stuck in blood vessels, blocking blood flow to the limbs and organs. Blocked blood vessels can cause pain, serious infections, and organ damage. Many patients with SCA also develop pulmonary hypertension.
Children and adolescents with SCA or Chuvash polycythemia (another blood disorder that carries an increased risk for pulmonary hypertension) may be eligible for this study.
Read more
Participants undergo the following procedures at the beginning (baseline) and end of the study:
- History, physical examination and blood tests .
- Echocardiography (ultrasound study of heart function).
- Transcranial doppler (brain ultrasound study to measure brain blood flow).
- Lung function tests.
- 6-minute walk (measure of the distance covered in 6 minutes of walking).
In addition, patients are followed by telephone or by clinic visits every 6 months for a review of their medical history and medications. A physical examination is also done at 12 months.
Read the detailed description
The research is designed to determine the prevalence and risk factors of pulmonary hypertension (PHT) in children and adolescents with sickle cell disease (SCD), and to determine the role of the hypoxic response in its pathogenesis. In this regard, proliferative vascular responses mediated by (i) hypoxia inducible factor (HIF)-regulated pathways and (ii) nitric oxide (NO)-scavenging will be compared between patients with SCD and patients with Chuvash polycythemia (CP), another hematological disorder characterized by increased risk for PHT. High throughput microarray and genotyping technologies will be employed to identify candidate gene pholymorphisms involved in pathologic responses to hypoxia in SCD and CP patients with and without PHT.
- Keywords
- 6-Minute Walk, Chuvash Polycythemia, Echocardiogram, Sickle Cell Anemia, Pulmonary Function Tests, Sickle Cell Disease, SCD, Pulmonary Hypertension
- Medical subject headings
- Cerebrovascular Disorders, Hypertension, Pulmonary, Anemia, Sickle Cell
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2007 (estimated)
- Study start28 Jun 2007
- Study completion2 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chuvash PolycythemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Time perspective
- Other
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Caterina P Minniti, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00495638
- Sponsor's protocol ID
- 070181
- Other IDs
- 07-H-0181
- Status last verified
- 2 Dec 2014
- First submitted
- 30 Jun 2007
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Sable CA, Aliyu ZY, Dham N, Nouraie M, Sachdev V, Sidenko S, Miasnikova GY, Polyakova LA, Sergueeva AI, Okhotin DJ, Bushuev V, Remaley AT, Niu X, Castro OL, Gladwin MT, Kato GJ, Prchal JT, Gordeuk VR. Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHL(R200W) mutation (Chuvash polycythemia). Haematologica. 2012 Feb;97(2):193-200. doi: 10.3324/haematol.2011.051839. Epub 2011 Oct 11.
PubMed 21993671Darbari DS, Onyekwere O, Nouraie M, Minniti CP, Luchtman-Jones L, Rana S, Sable C, Ensing G, Dham N, Campbell A, Arteta M, Gladwin MT, Castro O, Taylor JG 6th, Kato GJ, Gordeuk V. Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia. J Pediatr. 2012 Feb;160(2):286-90. doi: 10.1016/j.jpeds.2011.07.018. Epub 2011 Sep 3.
PubMed 21890147
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Hypertension and the Hypoxic Response in SCD
- ClinicalTrials.gov ID
- NCT00495638
- Acronym / sponsor ID
- 070181
- Keywords
- 6-Minute Walk, Chuvash Polycythemia, Echocardiogram, Sickle Cell Anemia, Pulmonary Function Tests, Sickle Cell Disease, SCD, Pulmonary Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 28 Jun 2007
- Study completion
- 2 Dec 2014
- First posted
- 3 Jul 2007 (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.
The study will look at the risk factors for pulmonary hypertension (high blood pressure in the lungs) in children and adolescents with sickle cell anemia (SCA) and examine the role of hypoxia (oxygen shortage) in the disease. In patients with SCA, red blood cells become sickle-shaped and tend to form clumps that get stuck in blood vessels, blocking blood flow to the limbs and organs. Blocked blood vessels can cause pain, serious infections, and organ damage. Many patients with SCA also develop pulmonary hypertension.
Children and adolescents with SCA or Chuvash polycythemia (another blood disorder that carries an increased risk for pulmonary hypertension) may be eligible for this study.
Participants undergo the following procedures at the beginning (baseline) and end of the study:
- History, physical examination and blood tests .
- Echocardiography (ultrasound study of heart function).
- Transcranial doppler (brain ultrasound study to measure brain blood flow).
- Lung function tests.
- 6-minute walk (measure of the distance covered in 6 minutes of walking).
In addition, patients are followed by telephone or by clinic visits every 6 months for a review of their medical history and medications. A physical examination is also done at 12 months.
Detailed description
The research is designed to determine the prevalence and risk factors of pulmonary hypertension (PHT) in children and adolescents with sickle cell disease (SCD), and to determine the role of the hypoxic response in its pathogenesis. In this regard, proliferative vascular responses mediated by (i) hypoxia inducible factor (HIF)-regulated pathways and (ii) nitric oxide (NO)-scavenging will be compared between patients with SCD and patients with Chuvash polycythemia (CP), another hematological disorder characterized by increased risk for PHT. High throughput microarray and genotyping technologies will be employed to identify candidate gene pholymorphisms involved in pathologic responses to hypoxia in SCD and CP patients with and without PHT.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 3 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (37 listed)
- For PAH in children and adolescents with SCD:
- The informed consent has been signed by the participant, parent or legal guardian as appropriate.
- Age of 3 to 20 years.
- Diagnosis of sickle cell disease (electrophoretic HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore is required).
- At least three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD.
Key exclusion criteria (32 listed)
- Age of less than 3 years or 21 years or more at time of enrollment.
- Presence of acute infection, pain crisis, injury, surgery, asthmatic episode or other acute complication.
- Hemoglobin A only phenotype, hemoglobin S trait or hemoglobin C trait.
- Less than three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD.
- Self-described ethnicity other than African American.
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
Not reported in the source record.
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 16 Dec 2019.
- Derived from this study: PubMed 21993671Sable CA, Aliyu ZY, Dham N, Nouraie M, Sachdev V, Sidenko S, Miasnikova GY, Polyakova LA, Sergueeva AI, Okhotin DJ, Bushuev V, Remaley AT, Niu X, Castro OL, Gladwin MT, Kato GJ, Prchal JT, Gordeuk VR. Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHL(R200W) mutation (Chuvash polycythemia). Haematologica. 2012 Feb;97(2):193-200. doi: 10.3324/haematol.2011.051839. Epub 2011 Oct 11.
- Derived from this study: PubMed 21890147Darbari DS, Onyekwere O, Nouraie M, Minniti CP, Luchtman-Jones L, Rana S, Sable C, Ensing G, Dham N, Campbell A, Arteta M, Gladwin MT, Castro O, Taylor JG 6th, Kato GJ, Gordeuk V. Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia. J Pediatr. 2012 Feb;160(2):286-90. doi: 10.1016/j.jpeds.2011.07.018. Epub 2011 Sep 3.
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.
Caterina P Minniti, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chuvash Polycythemia and Cerebrovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 7 sites in 2 countries.
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 37 inclusion and 32 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 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Russia. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00495638, which also lists 2 linked publications.
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 16 Dec 2019.