Sickle Cell DiseaseNCT03007849
A Pilot Study of Fecal Microbiome and Neutrophil Cellular Adhesion Molecules in Patients With Sickle Cell Disease (SCD)
An observational study of Sickle Cell Disease, run by Rhode Island Hospital.
Trial summary
Patients with sickle cell disease often develop painful crisis without any obvious reasons. Some patients are more likely to develop this complication than others. It is now clear that painful crisis only occurs when sickled red blood cells stick to white blood cells that have been activated, usually by inflammation… Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Dec 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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients with SCD attending the hematology clinic at Rhode Island Hospital will be invited to participate in this study. A total of 50 eligible patients will be accrued to the study. Participation in the study is voluntary and the subject will not receive any compensation.
Who may be able to join
- Both male and female will be accrued to the study, without any pre-specified sex ratio.
- Subject must have either HbSS or HbS/beta thal.
- Subject is >8 years of age; if subject is <18 years, parental consent is needed.
- Understands the process of and is willing to provide a written consent.
Who cannot join
- Is taking immunosuppressive agents, including corticosteroids with prednisone at a dose of > 30 mg/day or other forms of corticosteroid at the equivalent dose.
- Has taken systemic antimicrobials (except prophylactic Penicillin) in the preceding two weeks.
- Has had a vaso-occlusive crisis in the preceding two weeks.
- Has a history of colon cancer or an inflammatory bowel disease.
- Has a history of clostridium difficile infection in the preceding eight weeks.
- History of psychiatric disorder which in the investigators opinion may compromise compliance with the protocol or which does not allow for appropriate informed consent.
- Pregnant or lactating females.
- Patients who are court-mandated to reside at a treatment facility (e.g., drug or psychiatric treatment) or prison.
Trial locations and contacts
No sites are listed yet.
Nicholas Hebda, BA contact
About this study
Patients with sickle cell disease often develop painful crisis without any obvious reasons. Some patients are more likely to develop this complication than others. It is now clear that painful crisis only occurs when sickled red blood cells stick to white blood cells that have been activated, usually by inflammation or infections. A recent study in mice with sickle cell disease showed that the use of long term antibiotics could reduce the number of activated white blood cells and reduce death of the mice during sickle cell crisis.
The investigators believe that sickle cell patients who develop frequent painful crisis may have a different pattern of bacteria in their intestine when compared to those whose painful crisis occurs infrequently. In this study, the investigators propose to study sickle cell subject's blood to determine how many activated white blood cells he/she have. The investigators will also examine his/her stool to compare the bacteria in his/her stool to those other sickle cell patients. The investigators will then investigate whether or not the results from the blood and stool tests correlate with how frequently the patient develops painful crisis.
Read more
The investigators will examine the patients' medical records to find out how many times they have been admitted to the hospital for sickle cell crisis in the last 12 months. The investigators will also obtain information on the following: their age, their sex, whether they are taking hydroxyurea or Penicillin, when they last had a transfusion or exchange transfusion therapy and painful crisis needing hospital admission, whether they have received any antibiotics (other than Penicillin) in the last 4 weeks, and whether they are experiencing a painful crisis at the time that they enter the study. The investigators will obtain, from their previous laboratory results, their levels of hemoglobin F and markers of inflammation. The investigators will check their hemoglobin F level if they have not already had this tested.
The investigators expect to enroll 50 subjects into this study at Rhode Island Hospital/Hasbro Children's Hospital.
Read the detailed description
The clinical course of sickle cell disease (SCD) is very variable. Some patients experience vaso-occlusive disease infrequently, but other patients develop the complication recurrently. The reason for the difference remains unclear. Although erythrocyte sickling occurs due to factors such as dehydration, infections, extreme of temperatures, acidosis, and hypoxia, neutrophil adhesion and activation are crucial in eliciting the vaso-occlusive crisis in patients with SCD. Activated neutrophils upregulate the expression of various cellular adhesion molecules that increase their "stickiness" in vivo. A murine model of SCD demonstrated the importance of the intestinal microbiome in influencing the kinetics of ageing neutrophils. Depletion of the microbiota with prolonged courses of broad-spectrum systemic antibiotics resulted in a reduction of the number of these neutrophils and protection against LPS-induced fatal vaso-occlusive crisis in these mice.
Intestinal barrier is a functional barrier that separates the gut lumen from the inner host. It consists of mechanical elements (mucus, epithelial layer), humoral elements (defensins, IgA), immunologic elements (lymphocytes, innate immune cells), muscular and neurological element. Although the normal intestinal microbiota is the main source of endogenous pathogens, it also contributes to the functional integrity of the intestinal barrier through its interaction with the other components of the barrier. Failure of any of these components will result in a breakdown of the protective intestinal barrier with the consequence of recurrent intestinal-derived bacteremia/septicemia. A breakdown of the normal microbiome has been implicated in the development of various pathologic states, including Clostridium difficile infection, inflammatory bowel disease, intestinal graft-versus-host disease following allogeneic hematopoietic progenitor cell transplant, colon cancer, and metabolic disorders such as obesity and non-alcoholic steatohepatitis.
To explain the reason for the development of frequent vaso-occlusive crisis in some patients with SCD, the investigators' stepwise hypothesis is that, due to the sickling process and the consequent development of intestinal ischemia, patients with SCD, especially those with frequent vaso-occlusive crisis, are more likely to have altered microbiota than healthy individuals. If the normal microbiota is altered, the intestinal barrier will be compromised, rendering the patients more susceptible to recurrent bacteremia of intestinal origin. Since most SCD patients with vaso-occlusive crisis present without any obvious infections, it is likely that the compromised intestinal barrier facilitates an inoculum of bacteremia not high enough to cause overt infections but sufficient to activate neutrophils and elicit vaso-occlusive crisis. The first step towards testing this overall hypothesis is to test the sub-hypothesis that altered intestinal microbiomes correlate with increased number of activated neutrophils and frequent vaso-occlusive crisis in patients with SCD.
- Conditions
- 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.
Fecal microbiome
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
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
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seah Lim, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03007849
- Sponsor's protocol ID
- 021316
- Status last verified
- Dec 2016
- First submitted
- 29 Dec 2016
- Last updated
- 4 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Fecal Microbiome and Neutrophil Cellular Adhesion Molecules in Patients With Sickle Cell Disease (SCD)
- ClinicalTrials.gov ID
- NCT03007849
- Acronym / sponsor ID
- 021316
- Conditions
- Sickle Cell Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 2 Jan 2017 (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.
Patients with sickle cell disease often develop painful crisis without any obvious reasons. Some patients are more likely to develop this complication than others. It is now clear that painful crisis only occurs when sickled red blood cells stick to white blood cells that have been activated, usually by inflammation or infections. A recent study in mice with sickle cell disease showed that the use of long term antibiotics could reduce the number of activated white blood cells and reduce death of the mice during sickle cell crisis.
The investigators believe that sickle cell patients who develop frequent painful crisis may have a different pattern of bacteria in their intestine when compared to those whose painful crisis occurs infrequently. In this study, the investigators propose to study sickle cell subject's blood to determine how many activated white blood cells he/she have. The investigators will also examine his/her stool to compare the bacteria in his/her stool to those other sickle cell patients. The investigators will then investigate whether or not the results from the blood and stool tests correlate with how frequently the patient develops painful crisis.
The investigators will examine the patients' medical records to find out how many times they have been admitted to the hospital for sickle cell crisis in the last 12 months. The investigators will also obtain information on the following: their age, their sex, whether they are taking hydroxyurea or Penicillin, when they last had a transfusion or exchange transfusion therapy and painful crisis needing hospital admission, whether they have received any antibiotics (other than Penicillin) in the last 4 weeks, and whether they are experiencing a painful crisis at the time that they enter the study. The investigators will obtain, from their previous laboratory results, their levels of hemoglobin F and markers of inflammation. The investigators will check their hemoglobin F level if they have not already had this tested.
The investigators expect to enroll 50 subjects into this study at Rhode Island Hospital/Hasbro Children's Hospital.
Detailed description
The clinical course of sickle cell disease (SCD) is very variable. Some patients experience vaso-occlusive disease infrequently, but other patients develop the complication recurrently. The reason for the difference remains unclear. Although erythrocyte sickling occurs due to factors such as dehydration, infections, extreme of temperatures, acidosis, and hypoxia, neutrophil adhesion and activation are crucial in eliciting the vaso-occlusive crisis in patients with SCD. Activated neutrophils upregulate the expression of various cellular adhesion molecules that increase their "stickiness" in vivo. A murine model of SCD demonstrated the importance of the intestinal microbiome in influencing the kinetics of ageing neutrophils. Depletion of the microbiota with prolonged courses of broad-spectrum systemic antibiotics resulted in a reduction of the number of these neutrophils and protection against LPS-induced fatal vaso-occlusive crisis in these mice.
Intestinal barrier is a functional barrier that separates the gut lumen from the inner host. It consists of mechanical elements (mucus, epithelial layer), humoral elements (defensins, IgA), immunologic elements (lymphocytes, innate immune cells), muscular and neurological element. Although the normal intestinal microbiota is the main source of endogenous pathogens, it also contributes to the functional integrity of the intestinal barrier through its interaction with the other components of the barrier. Failure of any of these components will result in a breakdown of the protective intestinal barrier with the consequence of recurrent intestinal-derived bacteremia/septicemia. A breakdown of the normal microbiome has been implicated in the development of various pathologic states, including Clostridium difficile infection, inflammatory bowel disease, intestinal graft-versus-host disease following allogeneic hematopoietic progenitor cell transplant, colon cancer, and metabolic disorders such as obesity and non-alcoholic steatohepatitis.
To explain the reason for the development of frequent vaso-occlusive crisis in some patients with SCD, the investigators' stepwise hypothesis is that, due to the sickling process and the consequent development of intestinal ischemia, patients with SCD, especially those with frequent vaso-occlusive crisis, are more likely to have altered microbiota than healthy individuals. If the normal microbiota is altered, the intestinal barrier will be compromised, rendering the patients more susceptible to recurrent bacteremia of intestinal origin. Since most SCD patients with vaso-occlusive crisis present without any obvious infections, it is likely that the compromised intestinal barrier facilitates an inoculum of bacteremia not high enough to cause overt infections but sufficient to activate neutrophils and elicit vaso-occlusive crisis. The first step towards testing this overall hypothesis is to test the sub-hypothesis that altered intestinal microbiomes correlate with increased number of activated neutrophils and frequent vaso-occlusive crisis in patients with SCD.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients with SCD attending the hematology clinic at Rhode Island Hospital will be invited to participate in this study. A total of 50 eligible patients will be accrued to the study. Participation in the study is voluntary and the subject will not receive any compensation.
Key inclusion criteria (4 listed)
- Both male and female will be accrued to the study, without any pre-specified sex ratio.
- Subject must have either HbSS or HbS/beta thal.
- Subject is >8 years of age; if subject is <18 years, parental consent is needed.
- Understands the process of and is willing to provide a written consent.
Key exclusion criteria (8 listed)
- Is taking immunosuppressive agents, including corticosteroids with prednisone at a dose of > 30 mg/day or other forms of corticosteroid at the equivalent dose.
- Has taken systemic antimicrobials (except prophylactic Penicillin) in the preceding two weeks.
- Has had a vaso-occlusive crisis in the preceding two weeks.
- Has a history of colon cancer or an inflammatory bowel disease.
- Has a history of clostridium difficile infection in the preceding eight 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
Fecal microbiome
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2017.
- Individual participant dataSharing planned: No
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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.
Nicholas Hebda, BA contact
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Rhode Island Hospital.
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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 4 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Hebda, BA (nhebda@lifespan.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fecal microbiome (time frame: 1 year). 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 4 Jan 2017.