Sickle Cell DiseaseNCT01602809
Microvessels and Heart Problems in Sickle Cell Disease
An observational study of Sickle Cell Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Small blood vessels (microvessels) in many different organs are affected by diseases such as diabetes and atherosclerosis. These microvessels may also be abnormal in people who have sickle cell disease. Stiffness of the red blood cells leads to problems in the microvessels of the heart and kidneys. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2012to 25 Oct 2017
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult subject age greater than or equal to 18 years
- Able to give written informed consent
- For SCD groups, must have confirmed diagnosis of sickle cell disease
Who cannot join
- Atrial fibrillation or other irregular rhythm that would preclude adequate image acquisition
- Subjects with a contraindication for the ultrasound contrast agent.
- Pregnant or lactating women
- Known obstructive coronary or peripheral vascular disease
- SCD subjects at steady-state must not have acute pain crisis requiring intravenous analgesics within the prior 4 weeks
- SCD subjects in crisis must be within 72 hours of hospital admission
Show all 10Show fewer
- Subjects with contraindications to MRI scanning will complete all other procedures but will not undergo the MRI scan. Subjects with an estimated glomerular filtration rate of <30 ml/min/1.73 m(2) will not receive gadolinium as per 2011 NHLBI gadolinium administration policy.
- Subjects with a contraindication to regadenson
- Any condition that in the clinical opinion of the investigators renders study procedures inadvisable.
- Diagnosis of acute chest syndrome is not an exclusion criteria for this protocol. Subjects may be concurrently enrolled in any other protocols with the exception of investigational new drug studies.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Microvascular and Cardiac Dysfunction in Sickle Cell Disease
Background:
- Small blood vessels (microvessels) in many different organs are affected by diseases such as diabetes and atherosclerosis. These microvessels may also be abnormal in people who have sickle cell disease. Stiffness of the red blood cells leads to problems in the microvessels of the heart and kidneys. However, these problems may not be detected until these organs are severely affected. Researchers want to study problems with microvessels in people with and without sickle cell disease.
Read more
Objectives:
- To study how microvessels in the heart and other organs are affected by sickle cell disease.
Eligibility:
- Individuals at least 18 years of age who have sickle cell disease.
- Healthy volunteers at least 18 years of age.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- All participants will have about 3 to 4 hours of testing for the study. Participants with sickle cell disease who are having a pain crisis at the time they enter the study may be asked to have the testing again when the crisis is over. The repeat testing will occur at least 4 weeks after the pain crisis ends.
- All participants will have the following tests:
- Blood draws to check kidney and liver function, and other blood tests
- Measure of blood flow in the brachial (upper arm) artery
- Heart ultrasound
- Ultrasound scans of arm muscles to study blood flow
- Ultrasound scans after taking vasodilators to increase blood flow
- Healthy volunteers will also have a magnetic resonance imaging scan. It will show blood flow in the heart. This scan will involve another dose of a vasodilator.
Read the detailed description
Sickle cell disease is the most common genetic disease affecting African-Americans. It is characterized by an abnormal hemoglobin S, which polymerizes when deoxygenated leading to red cell rigidity and microvascular flow obstruction. Recurrent episodes of ischemia and a chronic inflammatory state lead to ischemia-reperfusion injury in multiple vital organ systems. Endothelial dysfunction has been demonstrated in patients with sickle cell disease and new therapies are targeted specifically towards the endothelium. Contrast ultrasound is a non-invasive technique that has been used to assess microvascular flow in coronary artery disease, diabetes, and other disease states. We propose to use this technique in sickle cell patients to compare their myocardial and skeletal muscle flow with that of normal controls, to detect changes during pain crisis, and to compare flow abnormalities with cardiac functional abnormalities.
- Conditions
- Sickle Cell Disease
- Keywords
- Perfusion, Microvessels, Ultrasound, Sickle Cell Disease
- Medical subject headings
- Anemia, Sickle Cell
What is being measured
The primary outcome is the main question the study is designed to answer.
To use contrast-enhanced ultrasound to evaluate microvascular blood flow (MBF) and capillary RBC velocity (CBV) in skeletal muscle and the heart (at rest and during vasodilator stress) in patients with SCD in comparison to normal control patient...
Secondary outcomes (2)
To determine whether MBF and CBV worsen during pain crisis in patients with SCD
To determine the relation between MBF and CBV and brachial artery flow or LV dysfunction.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2012 (estimated)
- Study start30 Apr 2012
- Study completion25 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies 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
- Prospective
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Vandana Sachdev, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602809
- Sponsor's protocol ID
- 120124
- Other IDs
- 12-H-0124
- Status last verified
- 25 Oct 2017
- First submitted
- 18 May 2012
- Last updated
- 27 Oct 2017
- Results posted
- No
Publications
Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol. 2009 Sep;84(9):618-25. doi: 10.1002/ajh.21475.
PubMed 19610078Hebbel RP, Osarogiagbon R, Kaul D. The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation. 2004 Mar;11(2):129-51.
PubMed 15280088Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA. Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol. 2000 Nov-Dec;22(6):515-20. doi: 10.1097/00043426-200011000-00009.
PubMed 11132219Sachdev V, Sidenko S, Wu MD, Minniti CP, Hannoush H, Brenneman CL, Waclawiw MA, Arai AE, Schechter AN, Kato GJ, Lindner JR. Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease. Br J Haematol. 2017 Nov;179(4):648-656. doi: 10.1111/bjh.14918. Epub 2017 Sep 7.
PubMed 28880374
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microvascular and Cardiac Dysfunction in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01602809
- Acronym / sponsor ID
- 120124
- Conditions
- Sickle Cell Disease
- Keywords
- Perfusion, Microvessels, Ultrasound, Sickle Cell Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 30 Apr 2012
- Study completion
- 25 Oct 2017
- First posted
- 21 May 2012 (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.
Background:
- Small blood vessels (microvessels) in many different organs are affected by diseases such as diabetes and atherosclerosis. These microvessels may also be abnormal in people who have sickle cell disease. Stiffness of the red blood cells leads to problems in the microvessels of the heart and kidneys. However, these problems may not be detected until these organs are severely affected. Researchers want to study problems with microvessels in people with and without sickle cell disease.
Objectives:
- To study how microvessels in the heart and other organs are affected by sickle cell disease.
Eligibility:
- Individuals at least 18 years of age who have sickle cell disease.
- Healthy volunteers at least 18 years of age.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- All participants will have about 3 to 4 hours of testing for the study. Participants with sickle cell disease who are having a pain crisis at the time they enter the study may be asked to have the testing again when the crisis is over. The repeat testing will occur at least 4 weeks after the pain crisis ends.
- All participants will have the following tests:
- Blood draws to check kidney and liver function, and other blood tests
- Measure of blood flow in the brachial (upper arm) artery
- Heart ultrasound
- Ultrasound scans of arm muscles to study blood flow
- Ultrasound scans after taking vasodilators to increase blood flow
- Healthy volunteers will also have a magnetic resonance imaging scan. It will show blood flow in the heart. This scan will involve another dose of a vasodilator.
Detailed description
Sickle cell disease is the most common genetic disease affecting African-Americans. It is characterized by an abnormal hemoglobin S, which polymerizes when deoxygenated leading to red cell rigidity and microvascular flow obstruction. Recurrent episodes of ischemia and a chronic inflammatory state lead to ischemia-reperfusion injury in multiple vital organ systems. Endothelial dysfunction has been demonstrated in patients with sickle cell disease and new therapies are targeted specifically towards the endothelium. Contrast ultrasound is a non-invasive technique that has been used to assess microvascular flow in coronary artery disease, diabetes, and other disease states. We propose to use this technique in sickle cell patients to compare their myocardial and skeletal muscle flow with that of normal controls, to detect changes during pain crisis, and to compare flow abnormalities with cardiac functional abnormalities.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult subject age greater than or equal to 18 years
- Able to give written informed consent
- For SCD groups, must have confirmed diagnosis of sickle cell disease
Key exclusion criteria (10 listed)
- Atrial fibrillation or other irregular rhythm that would preclude adequate image acquisition
- Subjects with a contraindication for the ultrasound contrast agent.
- Pregnant or lactating women
- Known obstructive coronary or peripheral vascular disease
- SCD subjects at steady-state must not have acute pain crisis requiring intravenous analgesics within the prior 4 weeks
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
To use contrast-enhanced ultrasound to evaluate microvascular blood flow (MBF) and capillary RBC velocity (CBV) in skeletal muscle and the heart (at rest and during vasodilator stress) in patients with SCD in comparison to normal control patient...
2 secondary outcomes
To determine whether MBF and CBV worsen during pain crisis in patients with SCD
To determine the relation between MBF and CBV and brachial artery flow or LV dysfunction.
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 27 Oct 2017.
- Background: PubMed 19610078Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol. 2009 Sep;84(9):618-25. doi: 10.1002/ajh.21475.
- Background: PubMed 15280088Hebbel RP, Osarogiagbon R, Kaul D. The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation. 2004 Mar;11(2):129-51.
- Background: PubMed 11132219Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA. Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol. 2000 Nov-Dec;22(6):515-20. doi: 10.1097/00043426-200011000-00009.
- Derived from this study: PubMed 28880374Sachdev V, Sidenko S, Wu MD, Minniti CP, Hannoush H, Brenneman CL, Waclawiw MA, Arai AE, Schechter AN, Kato GJ, Lindner JR. Skeletal and myocardial microvascular blood flow in hydroxycarbamide-treated patients with sickle cell disease. Br J Haematol. 2017 Nov;179(4):648-656. doi: 10.1111/bjh.14918. Epub 2017 Sep 7.
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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.
Vandana Sachdev, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site 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, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 3 inclusion and 10 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 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
To use contrast-enhanced ultrasound to evaluate microvascular blood flow (MBF) and capillary RBC velocity (CBV) in skeletal muscle and the heart (at rest and during vasodilator stress) in patients with SCD in comparison to normal control patient.... It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01602809, which also lists 4 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 27 Oct 2017.