Sickle Cell DiseaseNCT03111589
Monocytic Expression of Heme Oxidase-1 (HO-1) in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization.
A study testing Inactivated influenza A (H1N1) virus vaccine and Blood sampling in people with Sickle Cell Disease, run by Francis Corazza at 2 sites in Belgium.
Trial summary
Sickle cell disease (SCD) is an autosomal recessive disorder resulting from a substitution in the β chain of hemoglobin (Hb) which causes hemoglobin S to polymerize when deoxygenated. SCD patients present immune abnormalities that have always been attributed to functional asplenia. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Inactivated influenza A (H1N1) virus vaccine and Blood sampling
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 2 sitesBelgium
- Study dates
- Oct 2016to Oct 2018
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Pediatric and adult patients with sickle cell disease from the HUDERF and CHU-Brugmann Hospital
Who cannot join
- None
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Monocytic Expression of Heme Oxidase-1 (HO-1) in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization
Sickle cell disease (SCD) is an autosomal recessive disorder resulting from a substitution in the β chain of hemoglobin (Hb) which causes hemoglobin S to polymerize when deoxygenated. SCD patients present immune abnormalities that have always been attributed to functional asplenia. It it is now being recognized that patients with SCD have a pro-inflammatory condition with altered immune system activation contributing to the pathology of SCD. Increased levels of neutrophils, monocytes or cytokines have been reported in SCD patients.
SCD is associated with many acute and chronic complications requiring immediate support. Actual strongly recommended therapies include chronic blood transfusions (CT) and hydroxyurea (HU). In addition, episodic transfusions are recommended and commonly used to manage many acute SCD complications.There is strong evidence to support the use of HU in adults with 3 or more severe vaso-occlusive crises during any 12-month period, with SCD pain or chronic anemia, or with severe or recurrent episodes of acute chest syndrome. HU use is now also common in children with SCD. Some patients receive chronic monthly RBC transfusion with the objective to reduce the proportion of HbS to < 30 %. Long-term RBC transfusions prevent and treat complications of SCD decreasing the risk of stroke and the incidence of acute chest syndrome (ACS).
Read more
Therapeutic complications, such as alloimmunization against RBC in 20-50% of patients or hematopoietic stem cell transplantation (HSCT) graft rejection, constitute an immune-based clinical issue in SCD. Poorly understood RBC alloimmunization is responsible for serious hemolytic transfusion reaction associated with severe mortality and morbidity underlying the need for a better understanding of the immunology of SCD to improve SCD transfusion support/outcome. Little evidence exists about HU effects on immune functions in SCD. HU treatment doesn't appear to have deleterious effects on immune function and appears to decrease the abnormally elevated number of total WBC and lymphocytes, while CT does not.
Patients with SCD are at higher risk of infections and prophylactic vaccination is strongly recommended. Recent data suggest that vaccinal response to pneumococcal antigens in SCD patients is identical to healthy control while controversy concern the stability of the immune protection after vaccination of SCD patient. Antibody levels declined over the year and the need for more frequent vaccination in SCD patient should be investigated. Currently, there is no evidence whether HU may interfere with pneumococcal immune response. Purohit showed that immune response to inactivated influenza A (H1N1) virus vaccine was altered in patient with SCD receiving CT but little is known on immune response to vaccination in patients with SCD receiving HU.
Recent data suggest that not only inflammatory status but also humoral immune response to antigens in SCD patients may differ according to treatment. Yazdanbakhsh reported an imbalance between regulatory T cell (Treg) and effector T cell (Teff) in alloimmunized SCD patients with as consequence an increase in antibody production. In a model proposed by the authors, the balance between Treg and Teff is dictated by the monocyte control of cytokines expression. Altered activity of monocyte heme oxidase-1 (HO-1) would be responsible of a decrease in IL-12 and an increase in IL-10 cytokines secretion impacting the Treg/Teff cells ratio and promoting antibody production by B cells.
The objectives of the project are to assess whether different humoral immune responses to vaccines or to erythrocyte alloantigens are related to the type of treatment administered to patients with SCD. We also aim to study if these differences might be related to different expressions of HO-1 by monocytes.
- Conditions
- Sickle Cell Disease
- Being tested
- Inactivated influenza A (H1N1) virus vaccine, Blood sampling
- Keywords
- Sickle Cell Disease, Heme oxidase-1 (HO-1)
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inactivated influenza A (H1N1) virus vaccineBiological
All groups of patients and the control group will receive the new annually recommended inactivated influenza A (H1N1) virus vaccine.
Blood samplingDiagnostic test
Testing of the different humoral immune responses to vaccines or to erythrocyte alloantigens.
| Study group | Role | What they receive |
|---|---|---|
| SCD patients under regular chronic exchange transfusion | Experimental | Sickle cell disease patients (SCD) under regular chronic exchange transfusions. Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. Receives: Biological: Inactivated influenza A (H1N1) virus vaccine; Diagnostic Test: Blood sampling |
| SCD patients under HU treatment alone | Experimental | Sickle cell disease patients (SCD) under hydroxyurea (HU) alone. Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. Receives: Biological: Inactivated influenza A (H1N1) virus vaccine; Diagnostic Test: Blood sampling |
| SCD patients under HU treatment+sporadic transfusion | Experimental | Sickle cell disease patients (SCD) under hydroxyurea (HU) and receiving sporadic transfusions.Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. Receives: Biological: Inactivated influenza A (H1N1) virus vaccine; Diagnostic Test: Blood sampling |
| Control group | Active comparator | Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. Receives: Biological: Inactivated influenza A (H1N1) virus vaccine; Diagnostic Test: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracellular HO-1 expression in monocytes
Intracellular monocyte heme oxidase-1 (HO-1) expression will be measured by flow cytometry.The protein expression of HO-1 will be confirmed by Western blot. A commercial ELISA kit will be used in parallel to assess HO-1 levels in PBMC cell lysate.
Measured: 1 month post vaccination
HO-1 level in serum
Monocyte heme oxidase-1 (HO-1) level in serum will be measured by a commercial ELISA kit
Measured: 1 month post vaccination
Cytokines levels measurement
Pro-inflammatory cytokine (IL-12) and anti-inflammatory cytokine (IL-10) levels will be evaluated in serum and in IL-1 stimulated whole blood supernatants using an ELISA assay.
Measured: 1 month post vaccination
Identification of T regulatory cells
Evaluation of Treg cells in peripheral blood mononuclear cells (PBMC) will be performed by flow cytometry using appropriate fluorochrome conjugated monoclonal antibodies for CD25 and FoxP3 markers
Measured: 1 month post vaccination
Immune response to vaccination
Post-vaccination serum H1N1 antibodies titers (IgG and IgM) will be measured by an ELISA kit
Measured: 1 month post vaccination
Secondary outcomes (15)
Intracellular HO-1 expression in monocytes
Intracellular HO-1 expression will be measured by flow cytometry.The protein expression of HO-1 will be confirmed by Western blot. A commercial ELISA kit will be used in parallel to assess HO-1 levels in PBMC cell lysate.
Measured: Baseline: at vaccination
Intracellular HO-1 expression in monocytes
Intracellular HO-1 expression will be measured by flow cytometry.The protein expression of HO-1 will be confirmed by Western blot. A commercial ELISA kit will be used in parallel to assess HO-1 levels in PBMC cell lysate.
Measured: 3 months post vaccination
Intracellular HO-1 expression in monocytes
Intracellular HO-1 expression will be measured by flow cytometry.The protein expression of HO-1 will be confirmed by Western blot. A commercial ELISA kit will be used in parallel to assess HO-1 levels in PBMC cell lysate.
Measured: 6 months post vaccination
HO-1 level in serum
HO-1 level in serum will be measured by a commercial ELISA kit
Measured: Baseline: at vaccination
HO-1 level in serum
HO-1 level in serum will be measured by a commercial ELISA kit
Measured: 3 months post vaccination
HO-1 level in serum
HO-1 level in serum will be measured by a commercial ELISA kit
Measured: 6 months post vaccination
Cytokines levels measurement
Pro-inflammatory cytokine (IL-12) and anti-inflammatory cytokine (IL-10) levels will be evaluated in serum and in IL-1 stimulated whole blood supernatants using an ELISA assay.
Measured: Baseline: at vaccination
Cytokines levels measurement
Pro-inflammatory cytokine (IL-12) and anti-inflammatory cytokine (IL-10) levels will be evaluated in serum and in IL-1 stimulated whole blood supernatants using an ELISA assay.
Measured: 3 months post vaccination
Cytokines levels measurement
Pro-inflammatory cytokine (IL-12) and anti-inflammatory cytokine (IL-10) levels will be evaluated in serum and in IL-1 stimulated whole blood supernatants using an ELISA assay.
Measured: 6 months post vaccination
Identification of T regulatory cells
Evaluation of Treg cells in PBMC will be performed by flow cytometry using appropriate fluorochrome conjugated monoclonal antibodies for CD25 and FoxP3 markers
Measured: Baseline: at vaccination
Identification of T regulatory cells
Evaluation of Treg cells in PBMC will be performed by flow cytometry using appropriate fluorochrome conjugated monoclonal antibodies for CD25 and FoxP3 markers
Measured: 3 months post vaccination
Identification of T regulatory cells
Evaluation of Treg cells in PBMC will be performed by flow cytometry using appropriate fluorochrome conjugated monoclonal antibodies for CD25 and FoxP3 markers
Measured: 6 months post vaccination
Immune response to vaccination
Post-vaccination serum H1N1 antibodies titers (IgG and IgM) will be measured by an ELISA kit
Measured: Baseline: at vaccination
Immune response to vaccination
Post-vaccination serum H1N1 antibodies titers (IgG and IgM) will be measured by an ELISA kit
Measured: 3 months post vaccination
Immune response to vaccination
Post-vaccination serum H1N1 antibodies titers (IgG and IgM) will be measured by an ELISA kit
Measured: 6 months post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study startOct 2016
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Francis Corazza
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Francis Corazza, Brugmann University Hospital
- Investigators
- Francis Corazza, MD, Principal investigator, CHU Brugmann
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03111589
- Sponsor's protocol ID
- CHUB-HO1 sickle cell
- Status last verified
- Oct 2018
- First submitted
- 7 Apr 2017
- Last updated
- 18 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chintagari NR, Nguyen J, Belcher JD, Vercellotti GM, Alayash AI. Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease. Blood Cells Mol Dis. 2015 Mar;54(3):302-6. doi: 10.1016/j.bcmd.2014.12.001. Epub 2014 Dec 22.
PubMed 25582460Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M. Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol. 2012 Dec 1;189(11):5336-46. doi: 10.4049/jimmunol.1201028. Epub 2012 Oct 24.
PubMed 23100518De Montalembert M, Abboud MR, Fiquet A, Inati A, Lebensburger JD, Kaddah N, Mokhtar G, Piga A, Halasa N, Inusa B, Rees DC, Heath PT, Telfer P, Driscoll C, Al Hajjar S, Tozzi A, Jiang Q, Emini EA, Gruber WC, Gurtman A, Scott DA. 13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study. Pediatr Blood Cancer. 2015 Aug;62(8):1427-36. doi: 10.1002/pbc.25502. Epub 2015 Mar 23.
PubMed 25810327Hankins J, Jeng M, Harris S, Li CS, Liu T, Wang W. Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome. J Pediatr Hematol Oncol. 2005 Mar;27(3):158-61. doi: 10.1097/01.mph.0000157789.73706.53.
PubMed 15750449Lanaro C, Franco-Penteado CF, Albuqueque DM, Saad ST, Conran N, Costa FF. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy. J Leukoc Biol. 2009 Feb;85(2):235-42. doi: 10.1189/jlb.0708445. Epub 2008 Nov 12.
PubMed 19004988Lederman HM, Connolly MA, Kalpatthi R, Ware RE, Wang WC, Luchtman-Jones L, Waclawiw M, Goldsmith JC, Swift A, Casella JF; BABY HUG Investigators. Immunologic effects of hydroxyurea in sickle cell anemia. Pediatrics. 2014 Oct;134(4):686-95. doi: 10.1542/peds.2014-0571. Epub 2014 Sep 1.
PubMed 25180279Mohri T, Ogura H, Koh T, Fujita K, Sumi Y, Yoshiya K, Matsushima A, Hosotsubo H, Kuwagata Y, Tanaka H, Shimazu T, Sugimoto H. Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome. J Trauma. 2006 Sep;61(3):616-23; discussion 623. doi: 10.1097/01.ta.0000238228.67894.d7.
PubMed 16966997Nickel RS, Osunkwo I, Garrett A, Robertson J, Archer DR, Promislow DE, Horan JT, Hendrickson JE, Kean LS. Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy. Br J Haematol. 2015 May;169(4):574-83. doi: 10.1111/bjh.13326. Epub 2015 Mar 5.
PubMed 25753210Pathare A, Al Kindi S, Alnaqdy AA, Daar S, Knox-Macaulay H, Dennison D. Cytokine profile of sickle cell disease in Oman. Am J Hematol. 2004 Dec;77(4):323-8. doi: 10.1002/ajh.20196.
PubMed 15551290Purohit S, Alvarez O, O'Brien R, Andreansky S. Durable immune response to inactivated H1N1 vaccine is less likely in children with sickle cell anemia receiving chronic transfusions. Pediatr Blood Cancer. 2012 Dec 15;59(7):1280-3. doi: 10.1002/pbc.24206. Epub 2012 May 24.
PubMed 22628221Estcourt LJ, Fortin PM, Hopewell S, Trivella M, Wang WC. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database Syst Rev. 2017 Jan 17;1(1):CD003146. doi: 10.1002/14651858.CD003146.pub3.
PubMed 28094851Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.
PubMed 25203083Yazdanbakhsh K. Mechanisms of sickle cell alloimmunization. Transfus Clin Biol. 2015 Aug;22(3):178-81. doi: 10.1016/j.tracli.2015.05.005. Epub 2015 Jun 6.
PubMed 26056038
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocytic Expression of Heme Oxidase-1 (HO-1) in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization
- ClinicalTrials.gov ID
- NCT03111589
- Acronym / sponsor ID
- CHUB-HO1 sickle cell
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Heme oxidase-1 (HO-1)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Francis CorazzaUniversity, hospital or other
- Study start
- Oct 2016 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 13 Apr 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.
Sickle cell disease (SCD) is an autosomal recessive disorder resulting from a substitution in the β chain of hemoglobin (Hb) which causes hemoglobin S to polymerize when deoxygenated. SCD patients present immune abnormalities that have always been attributed to functional asplenia. It it is now being recognized that patients with SCD have a pro-inflammatory condition with altered immune system activation contributing to the pathology of SCD. Increased levels of neutrophils, monocytes or cytokines have been reported in SCD patients.
SCD is associated with many acute and chronic complications requiring immediate support. Actual strongly recommended therapies include chronic blood transfusions (CT) and hydroxyurea (HU). In addition, episodic transfusions are recommended and commonly used to manage many acute SCD complications.There is strong evidence to support the use of HU in adults with 3 or more severe vaso-occlusive crises during any 12-month period, with SCD pain or chronic anemia, or with severe or recurrent episodes of acute chest syndrome. HU use is now also common in children with SCD. Some patients receive chronic monthly RBC transfusion with the objective to reduce the proportion of HbS to < 30 %. Long-term RBC transfusions prevent and treat complications of SCD decreasing the risk of stroke and the incidence of acute chest syndrome (ACS).
Therapeutic complications, such as alloimmunization against RBC in 20-50% of patients or hematopoietic stem cell transplantation (HSCT) graft rejection, constitute an immune-based clinical issue in SCD. Poorly understood RBC alloimmunization is responsible for serious hemolytic transfusion reaction associated with severe mortality and morbidity underlying the need for a better understanding of the immunology of SCD to improve SCD transfusion support/outcome. Little evidence exists about HU effects on immune functions in SCD. HU treatment doesn't appear to have deleterious effects on immune function and appears to decrease the abnormally elevated number of total WBC and lymphocytes, while CT does not.
Patients with SCD are at higher risk of infections and prophylactic vaccination is strongly recommended. Recent data suggest that vaccinal response to pneumococcal antigens in SCD patients is identical to healthy control while controversy concern the stability of the immune protection after vaccination of SCD patient. Antibody levels declined over the year and the need for more frequent vaccination in SCD patient should be investigated. Currently, there is no evidence whether HU may interfere with pneumococcal immune response. Purohit showed that immune response to inactivated influenza A (H1N1) virus vaccine was altered in patient with SCD receiving CT but little is known on immune response to vaccination in patients with SCD receiving HU.
Recent data suggest that not only inflammatory status but also humoral immune response to antigens in SCD patients may differ according to treatment. Yazdanbakhsh reported an imbalance between regulatory T cell (Treg) and effector T cell (Teff) in alloimmunized SCD patients with as consequence an increase in antibody production. In a model proposed by the authors, the balance between Treg and Teff is dictated by the monocyte control of cytokines expression. Altered activity of monocyte heme oxidase-1 (HO-1) would be responsible of a decrease in IL-12 and an increase in IL-10 cytokines secretion impacting the Treg/Teff cells ratio and promoting antibody production by B cells.
The objectives of the project are to assess whether different humoral immune responses to vaccines or to erythrocyte alloantigens are related to the type of treatment administered to patients with SCD. We also aim to study if these differences might be related to different expressions of HO-1 by monocytes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SCD patients under regular chronic exchange transfusion | Experimental | Biological: Inactivated influenza A (H1N1) virus vaccine, Diagnostic Test: Blood samplingSickle cell disease patients (SCD) under regular chronic exchange transfusions. Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. |
| SCD patients under HU treatment alone | Experimental | Biological: Inactivated influenza A (H1N1) virus vaccine, Diagnostic Test: Blood samplingSickle cell disease patients (SCD) under hydroxyurea (HU) alone. Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. |
| SCD patients under HU treatment+sporadic transfusion | Experimental | Biological: Inactivated influenza A (H1N1) virus vaccine, Diagnostic Test: Blood samplingSickle cell disease patients (SCD) under hydroxyurea (HU) and receiving sporadic transfusions.Pediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. |
| Control group | Active comparator | Biological: Inactivated influenza A (H1N1) virus vaccine, Diagnostic Test: Blood samplingPediatric and adult patients from the HUDERF and CHU-Brugmann Hospitals. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Pediatric and adult patients with sickle cell disease from the HUDERF and CHU-Brugmann Hospital
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| Inactivated influenza A (H1N1) virus vaccineAll groups of patients and the control group will receive the new annually recommended inactivated influenza A (H1N1) virus vaccine. | Biological | Control group, SCD patients under HU treatment alone, SCD patients under HU treatment+sporadic transfusion, SCD patients under regular chronic exchange transfusion |
| Blood samplingTesting of the different humoral immune responses to vaccines or to erythrocyte alloantigens. | Diagnostic test | Control group, SCD patients under HU treatment alone, SCD patients under HU treatment+sporadic transfusion, SCD patients under regular chronic exchange transfusion |
Primary outcome
Intracellular HO-1 expression in monocytes
Time frame: 1 month post vaccination
Intracellular monocyte heme oxidase-1 (HO-1) expression will be measured by flow cytometry.The protein expression of HO-1 will be confirmed by Western blot. A commercial ELISA kit will be used in parallel to assess HO-1 levels in PBMC cell lysate.
HO-1 level in serum
Time frame: 1 month post vaccination
Monocyte heme oxidase-1 (HO-1) level in serum will be measured by a commercial ELISA kit
Cytokines levels measurement
Time frame: 1 month post vaccination
Pro-inflammatory cytokine (IL-12) and anti-inflammatory cytokine (IL-10) levels will be evaluated in serum and in IL-1 stimulated whole blood supernatants using an ELISA assay.
Identification of T regulatory cells
Time frame: 1 month post vaccination
Evaluation of Treg cells in peripheral blood mononuclear cells (PBMC) will be performed by flow cytometry using appropriate fluorochrome conjugated monoclonal antibodies for CD25 and FoxP3 markers
Immune response to vaccination
Time frame: 1 month post vaccination
Post-vaccination serum H1N1 antibodies titers (IgG and IgM) will be measured by an ELISA kit
15 secondary outcomes
Intracellular HO-1 expression in monocytes
Time frame: Baseline: at vaccination
Intracellular HO-1 expression in monocytes
Time frame: 3 months post vaccination
Intracellular HO-1 expression in monocytes
Time frame: 6 months post vaccination
HO-1 level in serum
Time frame: Baseline: at vaccination
HO-1 level in serum
Time frame: 3 months post vaccination
HO-1 level in serum
Time frame: 6 months post vaccination
Cytokines levels measurement
Time frame: Baseline: at vaccination
Cytokines levels measurement
Time frame: 3 months post vaccination
Cytokines levels measurement
Time frame: 6 months post vaccination
Identification of T regulatory cells
Time frame: Baseline: at vaccination
Identification of T regulatory cells
Time frame: 3 months post vaccination
Identification of T regulatory cells
Time frame: 6 months post vaccination
Immune response to vaccination
Time frame: Baseline: at vaccination
Immune response to vaccination
Time frame: 3 months post vaccination
Immune response to vaccination
Time frame: 6 months post vaccination
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 18 Oct 2018.
- Background: PubMed 25582460Chintagari NR, Nguyen J, Belcher JD, Vercellotti GM, Alayash AI. Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease. Blood Cells Mol Dis. 2015 Mar;54(3):302-6. doi: 10.1016/j.bcmd.2014.12.001. Epub 2014 Dec 22.
- Background: PubMed 23100518Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M. Prolonged neutrophil dysfunction after Plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol. 2012 Dec 1;189(11):5336-46. doi: 10.4049/jimmunol.1201028. Epub 2012 Oct 24.
- Background: PubMed 25810327De Montalembert M, Abboud MR, Fiquet A, Inati A, Lebensburger JD, Kaddah N, Mokhtar G, Piga A, Halasa N, Inusa B, Rees DC, Heath PT, Telfer P, Driscoll C, Al Hajjar S, Tozzi A, Jiang Q, Emini EA, Gruber WC, Gurtman A, Scott DA. 13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study. Pediatr Blood Cancer. 2015 Aug;62(8):1427-36. doi: 10.1002/pbc.25502. Epub 2015 Mar 23.
- Background: PubMed 15750449Hankins J, Jeng M, Harris S, Li CS, Liu T, Wang W. Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome. J Pediatr Hematol Oncol. 2005 Mar;27(3):158-61. doi: 10.1097/01.mph.0000157789.73706.53.
- Background: PubMed 19004988Lanaro C, Franco-Penteado CF, Albuqueque DM, Saad ST, Conran N, Costa FF. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy. J Leukoc Biol. 2009 Feb;85(2):235-42. doi: 10.1189/jlb.0708445. Epub 2008 Nov 12.
- Background: PubMed 25180279Lederman HM, Connolly MA, Kalpatthi R, Ware RE, Wang WC, Luchtman-Jones L, Waclawiw M, Goldsmith JC, Swift A, Casella JF; BABY HUG Investigators. Immunologic effects of hydroxyurea in sickle cell anemia. Pediatrics. 2014 Oct;134(4):686-95. doi: 10.1542/peds.2014-0571. Epub 2014 Sep 1.
- Background: PubMed 16966997Mohri T, Ogura H, Koh T, Fujita K, Sumi Y, Yoshiya K, Matsushima A, Hosotsubo H, Kuwagata Y, Tanaka H, Shimazu T, Sugimoto H. Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome. J Trauma. 2006 Sep;61(3):616-23; discussion 623. doi: 10.1097/01.ta.0000238228.67894.d7.
- Background: PubMed 25753210Nickel RS, Osunkwo I, Garrett A, Robertson J, Archer DR, Promislow DE, Horan JT, Hendrickson JE, Kean LS. Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy. Br J Haematol. 2015 May;169(4):574-83. doi: 10.1111/bjh.13326. Epub 2015 Mar 5.
- Background: PubMed 15551290Pathare A, Al Kindi S, Alnaqdy AA, Daar S, Knox-Macaulay H, Dennison D. Cytokine profile of sickle cell disease in Oman. Am J Hematol. 2004 Dec;77(4):323-8. doi: 10.1002/ajh.20196.
- Background: PubMed 22628221Purohit S, Alvarez O, O'Brien R, Andreansky S. Durable immune response to inactivated H1N1 vaccine is less likely in children with sickle cell anemia receiving chronic transfusions. Pediatr Blood Cancer. 2012 Dec 15;59(7):1280-3. doi: 10.1002/pbc.24206. Epub 2012 May 24.
- Background: PubMed 28094851Estcourt LJ, Fortin PM, Hopewell S, Trivella M, Wang WC. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database Syst Rev. 2017 Jan 17;1(1):CD003146. doi: 10.1002/14651858.CD003146.pub3.
- Background: PubMed 25203083Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.
- 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.
Francis Corazza, MD principal investigator
CHU Brugmann
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inactivated influenza A (H1N1) virus vaccine and Blood sampling in people with Sickle Cell Disease, run by Francis Corazza at 2 sites in Belgium.
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 1 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 18 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 2 sites in Belgium. 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?
Intracellular HO-1 expression in monocytes (time frame: 1 month post vaccination). The study lists 5 primary outcomes in all. 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 NCT03111589, which also lists 13 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 18 Oct 2018.