Sickle Cell DiseaseSTRESSNCT03368924
Implication of the Oxydative Stress in the Pathophysiology of Sickle Cell Anemia:
A study testing SCA patients (SS genotype) in people with Sickle Cell Disease, run by Centre Hospitalier Universitaire de la Guadeloupe at 1 site in Guadeloupe.
Trial summary
Despite important advances in the current understanding of sickle cell vaso-occlusion, the basis of its control and prevention remain partially unknown. The primary purpose is to test the hypothesis of a control of the sickle cell vaso-cocclusive (VOC) process by the anti band 3 antibodies by assessing the level of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- SCA patients (SS genotype)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteGuadeloupe
- Study dates
- 9 Apr 2013to 19 Sep 2015
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults ≥ 18 years old SCA patients (SS genotype) hospitalized for bone VOC with single or multifocal localizations.
Who cannot join
- chronic transfusion therapy or recent blood transfusion (less than 3 months before the current VOC or the state defined "steady-state" in SCA);
- severe chronic renal failure; liver failure;
- autoimmune disease;
- viral hepatitis; HIV seropositivity;
- pregnancy or breast feeding;
- patients already engaged in another therapeutic clinical research protocol; - non-compliant patients to usual care;
- patients unable to give their consent.
Trial locations and contacts
1 site in 1 country.
Guadeloupe1 site
Hospital University Center of Pointe-à-Pitre
Pointe-à-Pitre, 97159
About this study
Official title: Implication of the Oxydative Stress in the Pathophysiology of Sickle Cell Anemia: Vaso-occlusive Crises, Anti Bande 3 Antibodies Levels, Red Blood Cell Oxidation
Despite important advances in the current understanding of sickle cell vaso-occlusion, the basis of its control and prevention remain partially unknown. The primary purpose is to test the hypothesis of a control of the sickle cell vaso-cocclusive (VOC) process by the anti band 3 antibodies by assessing the level of these antibodies in the steady state and during the crises in SCA patients. To assess the relationship between the level of band 3 antibodies, the oxidation status, the expression of microparticles and the hemorheological alterations of the sickle red cells (SS RBs), the severity of VOC.
Read the detailed description
Although oxidative stress is not the primary aetiology of SCA, oxidative damage could in part account for pathophysiological mechanisms leading to sickle vaso-occlusion, in which anti bande 3 antibodies might play a role. Bande 3 is a protein belonging to red blood cells. These anti bande 3 antibodies are producted when after oxidative damage, a hidden site of bande 3 is revealed. In preliminary data, the Cuban partner of this study showed a significative difference between their level in patients, during steady state and vaso-occlusive crises. Our clinical question is to determine if a decrease of these antibodies, could participate in the occurrence of the crises. Therapeutic strategies aimed to counteract oxidative abnormalities might alleviate this still nowadays unknown mechanisms disease progression.
Band 3 protein which belongs to the anionic interchanger is the main erythrocyte membrane protein, present in about 1.2 x 106 copies per cell. Under certain conditions, band 3 protein modifications in the human erythrocyte membrane surface lead to band 3 aggregates. These modifications are mostly due to oxidative insults that gradually accumulate during red blood cell lifespan. Band 3 clusters on the SS RBCs produce two significant changes: first, these cells acquire an adhesive nature; second, band 3 aggregates are recognized by natural band 3 antibodies. Several studies have shown that band 3 peptides are able to inhibit the adherence of SS RBCs to endothelial cells. This suggests possible participation of band 3 antibodies in the aethiology as well as in the prevention of VOC in SCA. Oxidant damage in RBCs may contribute to the circulatory disorders by affecting their flow properties i.e. their deformability, aggregability and adherence to endothelial cells. Therefore, in parallel of the study of the evaluation of the role of anti bande 3 antibodies in VOC occurrence and severity, the investigators will explore the involvement of oxidative stress on the rheological properties of SSRBCs (deformability and aggregability),
- Conditions
- Sickle Cell Disease
- Being tested
- SCA patients (SS genotype)
- Keywords
- sickle cell anemia red blood cell oxidation, vaso-occlusive crises, anti bande 3 antibodies, red blood cell oxidation
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCA patients (SS genotype)Other
The clinical data relative to the patients will be collected in each of these stages (CVO, basic state).
Besides, to estimate the severity of the CVO, we shall use an index of severity of the episode ( IS2) adapted from the one who was validated by our group to stratify the severity of vasoocclusifs episodes at the drepanocytic child SS.
Main clinical parameters: taken of analgesic at home (level), temperature in the admission, SaO2 in the admission, number of painful sites, thoracic pain with or without associated cough, score EVA in the entrance, feeling of the patient of bigger gravity of the CVO with regard to its crises previous, heart rate to the admission, … Main biological parameters: rate of leukocytes, of polynucléaires neutrophiles, of réticulocytes, Lactate déshydrogénase, of haemoglobin, C-reactive Protein … The biological data can be studied according to their raw rate or according to their difference with their basic value (in the stable state).
| Study group | Role | What they receive |
|---|---|---|
| SCA patients (SS genotype) | Other | * To compare the level of anti band 3 antibodies in steady state and during vaso-occlusive crises in SCA patients.
* To assess the relationship between level of biomarkers of oxidation of SS RBCs, altered hemorheological parameters, biomarkers of cellular activation (microparticles) and anti band 3 antibodies rate, taking into account the alpha-globin genes status.
* To study the relationship between level of anti band 3 antibodies and severity of these VOC using an index of clinical severity (IS2) calculated at the end of SCA patients hospitalization for VOC.
* To study early clinical (including the activity of the autonomic nervous system activity) and biological items to evaluate the relationship between these items and severity of VOC. Receives: Other: SCA patients (SS genotype) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the level of anti band 3 antibodies in steady state and during vaso-occlusive crises in SCA patients.
Dosage of anti band 3 antibody during the steady state and the VOC
Measured: Through study completion, an average of 3 years
Secondary outcomes (3)
To assess the relationship between level of biomarkers of oxidation of SS RBCs, altered hemorheological parameters, biomarkers of cellular activation (microparticles) and anti band 3 antibodies rate, taking into account the alpha-globin genes status
Dosage of Parameters hémorhéologiques Dosage of the circulating microparticles Assessment of the level of oxidation of red blood cells
Measured: Through study completion, an average of 3 years
To study the relationship between level of anti band 3 antibodies and severity of these VOC using an index of clinical severity (IS2) calculated at the end of SCA patients hospitalization for VOC.
Dosage of anti band 3 antibody during the VOC Index of clinical severity (IS2)
Measured: Through study completion, an average of 3 years
To study early clinical (including the activity of the autonomic nervous system activity) and biological items to evaluate the relationship between these items and severity of VOC.
Dosage of Parameters hémorhéologiques Dosage of the circulating microparticles Assessment of the level of oxidation of red blood cells clinical evaluation
Measured: Through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2017
- Study start9 Apr 2013
- Primary completion19 Sep 2015
- Study completion19 Sep 2015
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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de la Guadeloupe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nathalie LEMONNE, Doctor specializing in SCA, Principal investigator, Hospital University Center of Pointe-à-Pitre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03368924
- Sponsor's protocol ID
- RBM-PAP-2012/47
- Acronym
- STRESS
- Status last verified
- Nov 2017
- First submitted
- 1 Dec 2017
- Last updated
- 11 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implication of the Oxydative Stress in the Pathophysiology of Sickle Cell Anemia: Vaso-occlusive Crises, Anti Bande 3 Antibodies Levels, Red Blood Cell Oxidation
- ClinicalTrials.gov ID
- NCT03368924
- Acronym / sponsor ID
- STRESS / RBM-PAP-2012/47
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell anemia red blood cell oxidation, vaso-occlusive crises, anti bande 3 antibodies, red blood cell oxidation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de la GuadeloupeUniversity, hospital or other
- Study start
- 9 Apr 2013 (actual)
- Primary completion
- 19 Sep 2015 (actual)
- Study completion
- 19 Sep 2015 (actual)
- First posted
- 11 Dec 2017 (actual)
- 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.
Despite important advances in the current understanding of sickle cell vaso-occlusion, the basis of its control and prevention remain partially unknown. The primary purpose is to test the hypothesis of a control of the sickle cell vaso-cocclusive (VOC) process by the anti band 3 antibodies by assessing the level of these antibodies in the steady state and during the crises in SCA patients. To assess the relationship between the level of band 3 antibodies, the oxidation status, the expression of microparticles and the hemorheological alterations of the sickle red cells (SS RBs), the severity of VOC.
Detailed description
Although oxidative stress is not the primary aetiology of SCA, oxidative damage could in part account for pathophysiological mechanisms leading to sickle vaso-occlusion, in which anti bande 3 antibodies might play a role. Bande 3 is a protein belonging to red blood cells. These anti bande 3 antibodies are producted when after oxidative damage, a hidden site of bande 3 is revealed. In preliminary data, the Cuban partner of this study showed a significative difference between their level in patients, during steady state and vaso-occlusive crises. Our clinical question is to determine if a decrease of these antibodies, could participate in the occurrence of the crises. Therapeutic strategies aimed to counteract oxidative abnormalities might alleviate this still nowadays unknown mechanisms disease progression.
Band 3 protein which belongs to the anionic interchanger is the main erythrocyte membrane protein, present in about 1.2 x 106 copies per cell. Under certain conditions, band 3 protein modifications in the human erythrocyte membrane surface lead to band 3 aggregates. These modifications are mostly due to oxidative insults that gradually accumulate during red blood cell lifespan. Band 3 clusters on the SS RBCs produce two significant changes: first, these cells acquire an adhesive nature; second, band 3 aggregates are recognized by natural band 3 antibodies. Several studies have shown that band 3 peptides are able to inhibit the adherence of SS RBCs to endothelial cells. This suggests possible participation of band 3 antibodies in the aethiology as well as in the prevention of VOC in SCA. Oxidant damage in RBCs may contribute to the circulatory disorders by affecting their flow properties i.e. their deformability, aggregability and adherence to endothelial cells. Therefore, in parallel of the study of the evaluation of the role of anti bande 3 antibodies in VOC occurrence and severity, the investigators will explore the involvement of oxidative stress on the rheological properties of SSRBCs (deformability and aggregability),
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SCA patients (SS genotype) | Other | Other: SCA patients (SS genotype)* To compare the level of anti band 3 antibodies in steady state and during vaso-occlusive crises in SCA patients. * To assess the relationship between level of biomarkers of oxidation of SS RBCs, altered hemorheological parameters, biomarkers of cellular activation (microparticles) and anti band 3 antibodies rate, taking into account the alpha-globin genes status. * To study the relationship between level of anti band 3 antibodies and severity of these VOC using an index of clinical severity (IS2) calculated at the end of SCA patients hospitalization for VOC. * To study early clinical (including the activity of the autonomic nervous system activity) and biological items to evaluate the relationship between these items and severity of VOC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adults ≥ 18 years old SCA patients (SS genotype) hospitalized for bone VOC with single or multifocal localizations.
Key exclusion criteria (7 listed)
- chronic transfusion therapy or recent blood transfusion (less than 3 months before the current VOC or the state defined "steady-state" in SCA);
- severe chronic renal failure; liver failure;
- autoimmune disease;
- viral hepatitis; HIV seropositivity;
- pregnancy or breast feeding;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SCA patients (SS genotype)The clinical data relative to the patients will be collected in each of these stages (CVO, basic state). Besides, to estimate the severity of the CVO, we shall use an index of severity of the episode ( IS2) adapted from the one who was validated by our group to stratify the severity of vasoocclusifs episodes at the drepanocytic child SS. Main clinical parameters: taken of analgesic at home (level), temperature in the admission, SaO2 in the admission, number of painful sites, thoracic pain with or without associated cough, score EVA in the entrance, feeling of the patient of bigger gravity of the CVO with regard to its crises previous, heart rate to the admission, … Main biological parameters: rate of leukocytes, of polynucléaires neutrophiles, of réticulocytes, Lactate déshydrogénase, of haemoglobin, C-reactive Protein … The biological data can be studied according to their raw rate or according to their difference with their basic value (in the stable state). | Other | SCA patients (SS genotype) |
Primary outcome
To compare the level of anti band 3 antibodies in steady state and during vaso-occlusive crises in SCA patients.
Time frame: Through study completion, an average of 3 years
Dosage of anti band 3 antibody during the steady state and the VOC
3 secondary outcomes
To assess the relationship between level of biomarkers of oxidation of SS RBCs, altered hemorheological parameters, biomarkers of cellular activation (microparticles) and anti band 3 antibodies rate, taking into account the alpha-globin genes status
Time frame: Through study completion, an average of 3 years
To study the relationship between level of anti band 3 antibodies and severity of these VOC using an index of clinical severity (IS2) calculated at the end of SCA patients hospitalization for VOC.
Time frame: Through study completion, an average of 3 years
To study early clinical (including the activity of the autonomic nervous system activity) and biological items to evaluate the relationship between these items and severity of VOC.
Time frame: Through study completion, an average of 3 years
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 11 Dec 2017.
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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.
Nathalie LEMONNE, Doctor specializing in SCA principal investigator
Hospital University Center of Pointe-à-Pitre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SCA patients (SS genotype) in people with Sickle Cell Disease, run by Centre Hospitalier Universitaire de la Guadeloupe at 1 site in Guadeloupe.
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 1 inclusion and 7 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 11 Dec 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 Guadeloupe. 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 compare the level of anti band 3 antibodies in steady state and during vaso-occlusive crises in SCA patients. (time frame: Through study completion, an average of 3 years). 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 11 Dec 2017.