Sickle Cell AnemiaNCT00113152
Heart Disease in Sickle Cell Anemia
An observational study of Sickle Cell Anemia and Pulmonary Hypertension, run by National Institutes of Health Clinical Center (CC) at 2 sites in United States.
Trial summary
This study will explore what may cause people with sickle cell anemia to have heart problems and an increased risk of sudden death. People 18 years of age and older with sickle cell anemia may be eligible for this study. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Sickle Cell Anemia, Pulmonary Hypertension
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Jun 2005to 2 Oct 2007
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Either gender, aged greater than 18 years
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S Beta-thalassemia genotype is required)
Who cannot join
- Pregnancy or lactation
- Known or suspected coronary artery disease
- Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal
- Cerebrovascular accident within the last six weeks
- New diagnosis of pulmonary embolism within the last three months
- History of retinal detachment
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- Patients with PAH known to be secondary to other causes, such as systemic lupus erythematosus, other collagen vascular diseases, valvular heart disease, congenital heart disease
- Patients who are intolerant of MRI will not undergo cardiac MRI
- Any other condition that would prevent participation in the study (for example HIV infection)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Suburban Hospital
Bethesda, Maryland, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Are Left Ventricular Abnormalities Associated With Pulmonary Hypertension in Sickle Cell Anemia?
This study will explore what may cause people with sickle cell anemia to have heart problems and an increased risk of sudden death.
People 18 years of age and older with sickle cell anemia may be eligible for this study. Candidates are screened with a medical history and physical examination, electrocardiogram (EKG), echocardiogram (heart ultrasound), and blood tests.
Read more
Participants undergo the following tests and procedures:
- Holter monitoring: The patient wears a small, battery-operated device to record heart rate and rhythm over 24 to 48 hours.
- QRST surface mapping: An EKG using 64 electrodes is done at rest and during exercise to provide a detailed look at the heart and its conduction system.
- Chest x-rays are taken to examine the lungs.
- Bicycle exercise echocardiography test: Blood pressure, pulse, heart rhythm and oxygen use are monitored while the patient exercises on a stationary bicycle. Ultrasound pictures are also obtained during the exercise.
- Echocardiogram: A heart ultrasound is done to check how well the heart is pumping blood.
- Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein and advanced to the chambers of the heart, through the heart valve and into the lung artery. The pressures in the heart and lung blood vessels are measured while the patient is resting and during exercise, with the bed tilted up and down, and after giving 500 mls of fluid into a vein.
- Blood tests are done to measure a hormone called brain natriuretic peptide, which can increase with the development of heart failure, and nitrite, a substance that can affect blood vessel dilation. Some blood is stored to test for inflammatory markers and for possible future gene and protein analysis.
- Cardiac magnetic resonance imaging (cMRI): The patient lies in a donut-shaped magnet while pictures of the heart are obtained using a magnetic field and radio waves. Earplugs are worn to muffle the loud sounds that occur with electrical switching of the magnetic fields. A contrast agent called gadolinium may be injected to enhance the quality of the images.
- Invasive electrocardiographic (reveal) monitoring: This procedure permits study of the heart rhythms over a long time period. A small device is placed just under the skin on the left side of the chest. It can be left in for up to 14 months to monitor the heartbeat continuously during this time.
Read the detailed description
Sickle cell anemia is an inherited blood disorder primarily affecting groups with origins in endemic malarial areas, especially those of African descent. SCA results from one of two single amino-acid substitutions in beta-hemoglobin (Hb-S and Hb-C) that increases the propensity for hemoglobin to polymerize, thus distorting, sickling and hemolyzing red cells. Individuals homozygous for Hb-S (or double heterozygote Hb-S and Hb-C) develop sickle cell anemia (SCA), while heterozygotes have sickle cell trait. SCA is characterized by chronic anemia and crises of red cell sickling and ischemia that are often painful and affect several organs and tissue types. SCA confers considerable disability, morbidity and mortality.
Annual mortality from SCA has been estimated at approximately 3%. As a significant number of these deaths are sudden, a cardiac cause has been suspected. However, no cardiac mechanism of sudden death (SD) has been clearly identified. Recently, it has been demonstrated that SCA patients with pulmonary hypertension (PAH) have a higher incidence of SD than those with normal pulmonary pressures. In many patients, PAH occurs in association with elevated pulmonary arterial wedge pressures and normal pulmonary arterial resistance, suggesting that the PAH develops as the result of left ventricular (LV) abnormalities. Furthermore, in other conditions in which PAH develops, SD occurs only at pressures considerably higher than those observed in SCA. These factors suggest that PAH in SCA is a surrogate marker for, rather than the cause of SD. Rather, an SCA cardiomyopathic process may provide a unifying mechanism that associates moderate degrees of PAH and high risk of SD from cardiac causes.
We propose to describe the extent of cardiac involvement in SCA. Specifically, we will (1) describe the LV volume-pressure relations in SCA patients with and without pulmonary hypertension in order to determine how elevated pulmonary pressures are related to dynamic filling properties of the LV; and (2) determine whether cardiac arrhythmias are common in SCA patients with PAH and if they contribute to SD.
Improved understanding of the etiology and mechanisms of SD in SCA may allow the development and testing of therapies for the primary prevention of SD.
- Conditions
- Sickle Cell Anemia, Pulmonary Hypertension
- Keywords
- Cardiac Arrhythmias, Diastolic Dysfunction, Pulmonary Hypertension, Sickle Cell Anemia, Sudden Death, Thalassemia
- Medical subject headings
- Anemia, Sickle Cell, Hypertension, Pulmonary, Arrhythmias, Cardiac, Death, Sudden, Thalassemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2005 (estimated)
- Study start2 Jun 2005
- Study completion2 Oct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell AnemiaStudies 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
- Enrolment
- 120 participants
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00113152
- Sponsor's protocol ID
- 050154
- Other IDs
- 05-CC-0154
- Status last verified
- 2 Oct 2007
- First submitted
- 3 Jun 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Charache S. Sickle cells and sudden death. J Lab Clin Med. 1994 Oct;124(4):473-4. No abstract available.
PubMed 7930871
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Are Left Ventricular Abnormalities Associated With Pulmonary Hypertension in Sickle Cell Anemia?
- ClinicalTrials.gov ID
- NCT00113152
- Acronym / sponsor ID
- 050154
- Conditions
- Sickle Cell Anemia, Pulmonary Hypertension
- Keywords
- Cardiac Arrhythmias, Diastolic Dysfunction, Pulmonary Hypertension, Sickle Cell Anemia, Sudden Death, Thalassemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 2 Jun 2005
- Study completion
- 2 Oct 2007
- First posted
- 6 Jun 2005 (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.
This study will explore what may cause people with sickle cell anemia to have heart problems and an increased risk of sudden death.
People 18 years of age and older with sickle cell anemia may be eligible for this study. Candidates are screened with a medical history and physical examination, electrocardiogram (EKG), echocardiogram (heart ultrasound), and blood tests.
Participants undergo the following tests and procedures:
- Holter monitoring: The patient wears a small, battery-operated device to record heart rate and rhythm over 24 to 48 hours.
- QRST surface mapping: An EKG using 64 electrodes is done at rest and during exercise to provide a detailed look at the heart and its conduction system.
- Chest x-rays are taken to examine the lungs.
- Bicycle exercise echocardiography test: Blood pressure, pulse, heart rhythm and oxygen use are monitored while the patient exercises on a stationary bicycle. Ultrasound pictures are also obtained during the exercise.
- Echocardiogram: A heart ultrasound is done to check how well the heart is pumping blood.
- Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein and advanced to the chambers of the heart, through the heart valve and into the lung artery. The pressures in the heart and lung blood vessels are measured while the patient is resting and during exercise, with the bed tilted up and down, and after giving 500 mls of fluid into a vein.
- Blood tests are done to measure a hormone called brain natriuretic peptide, which can increase with the development of heart failure, and nitrite, a substance that can affect blood vessel dilation. Some blood is stored to test for inflammatory markers and for possible future gene and protein analysis.
- Cardiac magnetic resonance imaging (cMRI): The patient lies in a donut-shaped magnet while pictures of the heart are obtained using a magnetic field and radio waves. Earplugs are worn to muffle the loud sounds that occur with electrical switching of the magnetic fields. A contrast agent called gadolinium may be injected to enhance the quality of the images.
- Invasive electrocardiographic (reveal) monitoring: This procedure permits study of the heart rhythms over a long time period. A small device is placed just under the skin on the left side of the chest. It can be left in for up to 14 months to monitor the heartbeat continuously during this time.
Detailed description
Sickle cell anemia is an inherited blood disorder primarily affecting groups with origins in endemic malarial areas, especially those of African descent. SCA results from one of two single amino-acid substitutions in beta-hemoglobin (Hb-S and Hb-C) that increases the propensity for hemoglobin to polymerize, thus distorting, sickling and hemolyzing red cells. Individuals homozygous for Hb-S (or double heterozygote Hb-S and Hb-C) develop sickle cell anemia (SCA), while heterozygotes have sickle cell trait. SCA is characterized by chronic anemia and crises of red cell sickling and ischemia that are often painful and affect several organs and tissue types. SCA confers considerable disability, morbidity and mortality.
Annual mortality from SCA has been estimated at approximately 3%. As a significant number of these deaths are sudden, a cardiac cause has been suspected. However, no cardiac mechanism of sudden death (SD) has been clearly identified. Recently, it has been demonstrated that SCA patients with pulmonary hypertension (PAH) have a higher incidence of SD than those with normal pulmonary pressures. In many patients, PAH occurs in association with elevated pulmonary arterial wedge pressures and normal pulmonary arterial resistance, suggesting that the PAH develops as the result of left ventricular (LV) abnormalities. Furthermore, in other conditions in which PAH develops, SD occurs only at pressures considerably higher than those observed in SCA. These factors suggest that PAH in SCA is a surrogate marker for, rather than the cause of SD. Rather, an SCA cardiomyopathic process may provide a unifying mechanism that associates moderate degrees of PAH and high risk of SD from cardiac causes.
We propose to describe the extent of cardiac involvement in SCA. Specifically, we will (1) describe the LV volume-pressure relations in SCA patients with and without pulmonary hypertension in order to determine how elevated pulmonary pressures are related to dynamic filling properties of the LV; and (2) determine whether cardiac arrhythmias are common in SCA patients with PAH and if they contribute to SD.
Improved understanding of the etiology and mechanisms of SD in SCA may allow the development and testing of therapies for the primary prevention of SD.
Study design
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Either gender, aged greater than 18 years
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S Beta-thalassemia genotype is required)
Key exclusion criteria (9 listed)
- Pregnancy or lactation
- Known or suspected coronary artery disease
- Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal
- Cerebrovascular accident within the last six weeks
- New diagnosis of pulmonary embolism within the last three months
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 2 Jul 2017.
- Background: PubMed 7930871Charache S. Sickle cells and sudden death. J Lab Clin Med. 1994 Oct;124(4):473-4. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 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 Anemia and Pulmonary Hypertension, run by National Institutes of Health Clinical Center (CC) at 2 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 2 inclusion and 9 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00113152, which also lists 1 linked publication.
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 2 Jul 2017.