Sickle Cell DiseaseNCT01568710
Blood Flow and Pain Crises in People With 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: Many people with sickle cell disease have repeated episodes of severe pain that lasts for days, requiring hospital care. These episodes, called pain crises, may be caused by changes in blood flow. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2012to 5 Oct 2018
- 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 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 years or older.
- African, of African descent or Hispanic
- Ability to provide informed written consent.
Who cannot join
- Pregnancy.
- History of non-trivial injury, burns, surgery or skin ulcers on the arms.
- Carrier of drug resistant bacteria that normally requires isolation while visiting a hospital.
- Administration of any of the following drugs within the last 14 days:
- Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil)
- Endothelin-1 receptor blockers (bosentan, sitaxentan, ambrisentan, tezosentan)
Show all 16Show fewer
- Nitric oxide donors (nitroglycerin, nitroprusside, nitrates)
- Ingestion of caffeine in the 12 hours before the start of the study appointment, or used tobacco in the 30 days before the study appointment.
- Diagnosis with any of the following chronic diseases or conditions:
- Sickle cell disease <TAB>
- Uncontrolled high blood pressure (systolic blood pressure must not be greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg)
- Uncontrolled high cholesterol (total cholesterol must not be greater than 240 mg/dL)
- Uncontrolled diabetes (must not have both a documented history of diabetes and random blood glucose of greater than 200 mg/dL)
- Chronic kidney disease (serum creatinine must not be greater than 2 mg/dL)
- Coronary artery disease
- Peripheral vascular disease
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: Measurement of the Reactive Hyperemia Index in Sickle Cell Patients During Pain Crisis and After Recovery
Background:
- Many people with sickle cell disease have repeated episodes of severe pain that lasts for days, requiring hospital care. These episodes, called pain crises, may be caused by changes in blood flow. Researchers want to study blood flow in people with sickle cell disease who are having a pain crisis and compare it with their blood flow after the pain crisis has resolved. They also want to compare these measurements against blood flow in healthy people who do not have sickle cell disease.
Read more
Objectives:
- To study whether changes in blood flow cause pain crises in people with sickle cell disease.
Eligibility:
- Individuals at least 18 years of age who have sickle cell disease and are being treated for a pain crisis.
- Individuals at least 18 years of age who have sickle cell disease and are not experiencing a pain crisis.
- Healthy volunteers matched by age and gender with the participants who have sickle cell disease.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Participants having a sickle cell pain crisis will have two visits, one during the crisis and one about 4 weeks after the crisis has resolved.
- Participants not having a sickle cell pain crisis will have one or two study visits. Blood samples will be collected during at least one of these visits.
- Healthy volunteers will have one or two study visits. Blood samples will be collected during at least one of these visits.
- During each visit for all participants, cameras and blood flow monitoring equipment will be used to measure blood flow in the forearm. sickle cell disease.
Read the detailed description
Severe recurrent pain is the most common cause of acute morbidity in sickle cell disease1. The underlying pathogenesis was initially thought to be ischemia from obstruction of capillary beds by stiffened red blood cells; however, there is evidence that other factors contribute to the pathogenesis of sickle cell pain crisis, such as inflammation and coagulation, ischemia-reperfusion injury, angiogenesis balance, and vasomotor tone processes that are regulated by endothelial nitric oxide.
Recent clinical data suggest that subjects with sickle cell disease suffer from chronically impaired nitric oxide bioavailability. This has been attributed to increased consumption of nitric oxide by hemoglobin and reactive oxygen species, or decreased production of nitric oxide by endothelial cells; however the roles of nitric oxide bioavailability and endothelial dysfunction during acute pain crisis are controversial and incompletely understood. Although there have been several studies of endothelial function in steady state sickle cell disease, there has been no comprehensive study of endothelial function during pain crisis.
In this study, our primary objective is to measure the reactive hyperemia index (a measure of the endothelial response to shear stress) in twenty sickle cell subjects during acute pain crisis and to compare it with the reactive hyperemia index measured after recovery from pain crisis. This will identify whether there are acute changes in endothelial cell function during sickle cell pain crisis. Our secondary objective is to compare the reactive hyperemia index of thirty-five sickle cell subjects in steady state versus the reactive hyperemia index of thirty-five healthy control subjects. This will identify whether there are chronic differences in endothelial function between sickle cell subjects and healthy control subjects.
This study will determine if there are defects in endothelium-dependent vasodilation in response to shear stress during sickle cell pain crisis. Moreover, this study provides an opportunity to evaluate new physiologic biomarkers of sickle cell pain crisis based on measurements of blood flow, temperature, and oxygenation in the skin. These measurements may serve as clinical endpoints in future studies of disease pathogenesis or therapeutic interventions for sickle cell disease.
- Conditions
- Sickle Cell Disease
- Keywords
- Blood Flow, Endothelium, Nitric Oxide, Oximetry, Laser Doppler, Sickle Cell Disease
- Medical subject headings
- 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 posted2 Apr 2012 (estimated)
- Study start21 Mar 2012
- Study completion5 Oct 2018
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
- 94 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institute for Biomedical Imaging and Bioengineering (NIBIB)
- Responsible party
- Sponsor
- Investigators
- Hans C Ackerman, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01568710
- Sponsor's protocol ID
- 120101
- Other IDs
- 12-H-0101
- Status last verified
- 5 Oct 2018
- First submitted
- 30 Mar 2012
- Last updated
- 9 Oct 2018
- Results posted
- No
Publications
Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6. doi: 10.1056/NEJM199107043250103.
PubMed 1710777Nagel RL. Sickle cell anemia is a multigene disease: sickle painful crises, a case in point. Am J Hematol. 1993 Jan;42(1):96-101. doi: 10.1002/ajh.2830420119. No abstract available.
PubMed 8416304Hebbel RP, Vercellotti GM. The endothelial biology of sickle cell disease. J Lab Clin Med. 1997 Mar;129(3):288-93. doi: 10.1016/s0022-2143(97)90176-1. No abstract available.
PubMed 9042813Rowley CA, Ikeda AK, Seidel M, Anaebere TC, Antalek MD, Seamon C, Conrey AK, Mendelsohn L, Nichols J, Gorbach AM, Kato GJ, Ackerman H. Microvascular oxygen consumption during sickle cell pain crisis. Blood. 2014 May 15;123(20):3101-4. doi: 10.1182/blood-2013-11-533406. Epub 2014 Mar 24.
PubMed 24665133
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of the Reactive Hyperemia Index in Sickle Cell Patients During Pain Crisis and After Recovery
- ClinicalTrials.gov ID
- NCT01568710
- Acronym / sponsor ID
- 120101
- Conditions
- Sickle Cell Disease
- Keywords
- Blood Flow, Endothelium, Nitric Oxide, Oximetry, Laser Doppler, Sickle Cell Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institute for Biomedical Imaging and Bioengineering (NIBIB)
- Study start
- 21 Mar 2012
- Study completion
- 5 Oct 2018
- First posted
- 2 Apr 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:
- Many people with sickle cell disease have repeated episodes of severe pain that lasts for days, requiring hospital care. These episodes, called pain crises, may be caused by changes in blood flow. Researchers want to study blood flow in people with sickle cell disease who are having a pain crisis and compare it with their blood flow after the pain crisis has resolved. They also want to compare these measurements against blood flow in healthy people who do not have sickle cell disease.
Objectives:
- To study whether changes in blood flow cause pain crises in people with sickle cell disease.
Eligibility:
- Individuals at least 18 years of age who have sickle cell disease and are being treated for a pain crisis.
- Individuals at least 18 years of age who have sickle cell disease and are not experiencing a pain crisis.
- Healthy volunteers matched by age and gender with the participants who have sickle cell disease.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Participants having a sickle cell pain crisis will have two visits, one during the crisis and one about 4 weeks after the crisis has resolved.
- Participants not having a sickle cell pain crisis will have one or two study visits. Blood samples will be collected during at least one of these visits.
- Healthy volunteers will have one or two study visits. Blood samples will be collected during at least one of these visits.
- During each visit for all participants, cameras and blood flow monitoring equipment will be used to measure blood flow in the forearm. sickle cell disease.
Detailed description
Severe recurrent pain is the most common cause of acute morbidity in sickle cell disease1. The underlying pathogenesis was initially thought to be ischemia from obstruction of capillary beds by stiffened red blood cells; however, there is evidence that other factors contribute to the pathogenesis of sickle cell pain crisis, such as inflammation and coagulation, ischemia-reperfusion injury, angiogenesis balance, and vasomotor tone processes that are regulated by endothelial nitric oxide.
Recent clinical data suggest that subjects with sickle cell disease suffer from chronically impaired nitric oxide bioavailability. This has been attributed to increased consumption of nitric oxide by hemoglobin and reactive oxygen species, or decreased production of nitric oxide by endothelial cells; however the roles of nitric oxide bioavailability and endothelial dysfunction during acute pain crisis are controversial and incompletely understood. Although there have been several studies of endothelial function in steady state sickle cell disease, there has been no comprehensive study of endothelial function during pain crisis.
In this study, our primary objective is to measure the reactive hyperemia index (a measure of the endothelial response to shear stress) in twenty sickle cell subjects during acute pain crisis and to compare it with the reactive hyperemia index measured after recovery from pain crisis. This will identify whether there are acute changes in endothelial cell function during sickle cell pain crisis. Our secondary objective is to compare the reactive hyperemia index of thirty-five sickle cell subjects in steady state versus the reactive hyperemia index of thirty-five healthy control subjects. This will identify whether there are chronic differences in endothelial function between sickle cell subjects and healthy control subjects.
This study will determine if there are defects in endothelium-dependent vasodilation in response to shear stress during sickle cell pain crisis. Moreover, this study provides an opportunity to evaluate new physiologic biomarkers of sickle cell pain crisis based on measurements of blood flow, temperature, and oxygenation in the skin. These measurements may serve as clinical endpoints in future studies of disease pathogenesis or therapeutic interventions for sickle cell disease.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18 years or older.
- African, of African descent or Hispanic
- Ability to provide informed written consent.
Key exclusion criteria (16 listed)
- Pregnancy.
- History of non-trivial injury, burns, surgery or skin ulcers on the arms.
- Carrier of drug resistant bacteria that normally requires isolation while visiting a hospital.
- Administration of any of the following drugs within the last 14 days:
- Ingestion of caffeine in the 12 hours before the start of the study appointment, or used tobacco in the 30 days before the study appointment.
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.
3 secondary outcomes
Skin Blood Flood
Time frame: 1 month
Skin Temperature
Time frame: 1 month
Tissue oxygenation
Time frame: 1 month
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 9 Oct 2018.
- Background: PubMed 1710777Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6. doi: 10.1056/NEJM199107043250103.
- Background: PubMed 8416304Nagel RL. Sickle cell anemia is a multigene disease: sickle painful crises, a case in point. Am J Hematol. 1993 Jan;42(1):96-101. doi: 10.1002/ajh.2830420119. No abstract available.
- Background: PubMed 9042813Hebbel RP, Vercellotti GM. The endothelial biology of sickle cell disease. J Lab Clin Med. 1997 Mar;129(3):288-93. doi: 10.1016/s0022-2143(97)90176-1. No abstract available.
- Derived from this study: PubMed 24665133Rowley CA, Ikeda AK, Seidel M, Anaebere TC, Antalek MD, Seamon C, Conrey AK, Mendelsohn L, Nichols J, Gorbach AM, Kato GJ, Ackerman H. Microvascular oxygen consumption during sickle cell pain crisis. Blood. 2014 May 15;123(20):3101-4. doi: 10.1182/blood-2013-11-533406. Epub 2014 Mar 24.
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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.
Hans C Ackerman, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 16 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 9 Oct 2018. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01568710, 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 9 Oct 2018.