Sickle Cell Disease (SCD)

The purpose of this feasibility study is to investigate the role of a dietary supplement in modulating the gut microbiota and improving pain outcomes in children with sickle cell disease (SCD).

The goal of this study is to evaluate if patients with sickle cell disease can achieve a maximum tolerate dose of hydroxuyrea (HU) over a period of 12 months faster with pharmacokinetic testing than the standard of care bloodwork follow-up. Pharmacokinetic test is used to evaluate the process by which drugs are absorbed, distributed in the body, localized in the tissues, and is excreted. Patient will be a randomized (coin toss method) into 2 groups. Group A will have an increase of their HU dosage with pharmacokinetic results and Group B will have an increase of their HU dosage following the standard of care bloodwork follow-up. Group C will include patient with sickle cell disease that has been taking HU for at least 12 months and will undergo a pharmacokinetic dosage to check the level of HU only one time.

The purpose of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).

Sickle cell disease (SCD) is a severe hemoglobinopathy, considered the first monogenic disease in the world. Acute chest syndrome (ACS), one of the most frequent and serious complications of SCD, is defined by the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging. ACS is characterized by lung consolidation, severe pulmonary vascular dysfunction, with potential role for regional alveolar hypoxia. Therefore, improving alveolar oxygenation and limiting lung consolidation are key objectives of the treatment of ACS, in addition to ensuring pain relief and giving blood transfusions and antibiotics. Bilevel non-invasive ventilation failed in improving outcomes during ACS (Fartoukh 2010). These results are in accordance with those reported in other forms of acute lung injury (Frat 2015), with conflicting results. Among other explanations, NIV may favour high tidal volume ventilation leading to patient self-inflicted lung injury (P-SILI) (Carteaux 2016). Continuous positive airway pressure (CPAP) is a simple to use and affordable technique for non-invasive ventilatory support, that theoretically exposes to a lower risk of P-SILI (Carteaux 2021). In patients with acute hypoxemic respiratory failure (AHRF), applying a positive pressure to the airway opening has been shown to mitigate the reduction in functional residual capacity and to improve respiratory mechanics and gas exchange. In a randomized controlled trial (RCT) conducted in patients with AHRF, CPAP achieved early physiologic improvement (Delclaux 2000). Recent results also suggest that CPAP reduces the composite outcome of intubation or death in adults with AHRF due to COVID-19 in a large multicentre study (RECOVERY-R) (Perkins 2022). In addition, CPAP can be safely used at early stages in the wards, with a frugal approach, using virtual valves (Carteaux 2021). In patients with SCD, CPAP has shown benefits when used at night in children with sleep apnea (Marshall 2009), or for the peri-operative management (Leff 2007). CPAP is also used in clinical practice for hypoxemic ACS (Heilbronner 2021), but it has not been formally assessed in this setting.

The goal of this study is to learn if Ketamine works more efficiently, as compared to Opioids, for Sickle Cell Pain The main questions it aims to answer are: Does Ketamine lower the number of times participants need to be admitted for continued pain control during a Sickle Cell Pain Crisis. Does Ketamine decrease the amount of time it takes to reach adequate pain control/pain score improvement, as compared to Opioids. Patients could have too low or too high blood pressure or sleepiness. Researchers will compare Ketamine to Opioids (Morphine or Dilaudid) to see if Ketamine works to treat pain enough that you do not need to be admitted to the hospital. Participants will: On arrival to the Children's ER for Sickle Cell Pain crisis will get Ketamine, instead of Morphine or Dilaudid, along with the typical Tylenol, Toradol, Lidocaine patch for pain control while in the ER. During this time we will follow your reported pain scale (0-10) to monitor your pain response to the Ketamine, as well as follow rate of hospital admission.

Children with sickle cell disease are at high risk of invasive bacterial infections, which may lead to serious complications. Preventive measures, including antibiotic prophylaxis and vaccination, have changed the epidemiology of these infections over time. New pneumococcal conjugate vaccines have recently become available, and updated data are needed to better understand which bacteria are currently responsible for invasive infections in this population. The aim of this retrospective study is to describe the bacterial distribution of invasive bacterial infections in children with sickle cell disease in France between 2020 and 2025. The results may help improve knowledge of these infections and guide future prevention strategies, including antibiotic management and vaccination policies.

The WeDecide study is a large observational study comparing the long-term effects of matched related donor hematopoietic stem cell transplantation (MRD HCT) and non-transplant disease-modifying therapies (NT-DMT) for pediatric patients with sickle cell disease (SCD). The study aims to assess health-related quality of life (HRQoL), cognitive function, risks, and benefits of both treatments, including survival rates, chronic complications, and organ damage prevention. With 160 children in the MRD HCT group and 320 in the NT-DMT group, aged 3-20.9 years, the study will follow participants for three years, examining factors like disease severity, treatment history, and social determinants of health. By providing a comprehensive comparison, the study seeks to inform clinical decisions and improve understanding of SCD treatment outcomes, ultimately supporting families and healthcare providers in choosing the best treatment options.

This research is being conducted to see if using an injectable contraception, Depot Medroxyprogesterone Acetate (Depo-Provera), can reduce the pain experienced by women with sickle cell disease. Participants in this study will be adult women with sickle cell disease who regularly experience sickle cell pain. They will complete a 3-month "baseline "with no use of hormonal contraception, and then a 3-month follow-up after receiving an injection of Depo-Provera. Participants will complete 6 to 7 in-person visits with a urine pregnancy test, blood draw, and surveys, as well as complete remote weekly surveys and monthly home pregnancy tests.

The goal of this interventional study is to learn about the impact of an intervention for health care providers that teaches individuation and perspective-taking (IPT) skills to enhance patient-centered communication in pediatric sickle cell disease (SCD). The main question it aims to answer is: Does an intervention that teaches individuation and perspective-taking (IPT) skills to pediatric sickle cell disease (SCD) health care providers (HCPs) enhance patient-centered communication? Researchers will compare the IPT intervention to a control group who will receive education about SCD pain management to see if the IPT intervention improves patient-centered communication. Participants will complete baseline surveys and then be randomly assigned into the intervention or control group. After completing their assigned session (IPT training or education), they will be asked to complete the same surveys as completed at baseline.

Kidney disease is a major cause of illness and death in people with sickle cell disease and sickle cell trait. Despite these concerning facts, we do not (1) have an in-depth understanding of how kidney disease starts in sickle cell disease and sickle cell trait, (2) have detailed insights into why kidney disease is worse in people with sickle cell disease and sickle cell trait, (3) have management options that are tailored to treating or preventing kidney disease in people with sickle cell disease or sickle cell trait. The SCeK Biorepository is a specialized, secure repository designed for the collection of blood and urine samples from people with sickle cell disease and sickle cell trait. These samples are connected to detailed medical records, with the sole purpose of allowing researchers to better understand how kidney disease starts and progresses in people with the sickle cell gene. By studying these stored samples (using new tests) together with health information, researchers can find better early warning signs of kidney injury and develop better ways to protect kidney health in people with sickle cell disease and sickle cell trait.

The goal of this clinical trial is to learn if a multifaceted intervention composed of Gazelle-Multispectral sickle cell disease (SCD) point of care testing (POCT) and early initiation of comprehensive SCD care in children with SCD disease aged 0 - 6 months can improve their clinical outcomes. The main questions it aims to answer are: * Does the intervention lower the number of SCD-related illnesses? * Does the intervention lower the illness incidence defined as seeking health care at any health facility - with or without treatment - for any episode related to a SCD related illness? * Does the intervention lower all-cause death rate (at the end of 1, 2, 3 and 3.5 years of follow-up)? Researchers will compare the multifaceted intervention results with those of historical data (based on erratic SCD testing and treatment) from the region. Participants will undergo a SCD screening test using the Gazelle Multispectral platform and if positive they will undergo confirmatory testing with HemoTypeSC™. Participants with SCD will receive early comprehensive clinical interventions i.e. standard administration of antibacterial and antimalarial prophylaxis, vaccinations for pneumococcal and Haemophilus influenzae type b (Hib), hydroxyurea, parental education about the need for regular and, if necessary, urgent medical care.

Sickle cell disease (or sickle cell anemia) is the most common genetic disease in France with 586 children screened in 2019. This chronic disease is characterized by the presence of abnormal Hemoglobin (Hb) S and a deformation of the red blood cells which take the elongated shape of a sickle and become more rigid and more fragile. Sickle cell disease manifests itself among other things by very painful vaso-occlusive crises (VOC) and for some chronic pain. Their management is an emergency and often requires hospitalization. Despite analgesic treatment, some patients have persistent pain. In 2013, a childcare assistant trained in Canadian global reflexology EMC offered reflexology sessions to 12 sickle cell patients. She observed a relief in all patients with a decrease in the pain score in 8 of them. These sessions seem to show us a double interest: the reduction of the child\'s pain and the emergence of a technique that can be used by paramedics in the context of their own role. The investgators hypothesize that global reflexology is an effective and acceptable complementary technique for pain management in addition to the usual analgesic management in sickle cell children under 18 years of age in CVO. In order to verify our hypothesis, the investigators propose to explore the practice of Canadian global reflexology as an innovative therapeutic option complementary to drug treatments in the hospital management of sickle cell children.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, painful crisis called vaso-occlusive crisis (VOC) and chronic inflammation. Activated platelets of SCD patients participated to both chronic inflammation and painful VOC. Platelets are anucleated cells from the fragmentation of megakaryocytes in bone marrow. The main aim of this study is to characterize the distribution of the different megakaryocyte subpopulations of sickle cell disease patients SS and SC and in particular the "immune" megakaryocytes CD148+CD48+ and to compare it with the platelet phenotype.

Sickle cell disease is the most common inherited blood disorder in the world. Chronic hemolysis induces platelet activation and chronic inflammation. Platelets and megakaryocyte, as medullar platelets precursors, are known to play a role in innate immunity. Little is known about the role of megakaryocytes at basal state and during acute complication in sickle cell disease patients. The aim of this study is to evaluate the role of megakaryocytes in sickle cell disease.

Sickle cell disease is characterized by chronic hemolytic anemia and blood rheological alterations. In addition, blood coagulation abnormalities have been reported in patients with sickle cell disease and hemolysis-derived products could be involved. The investigators hypothesized that patients with sickle cell disease and severe hemolysis (Lactate Dehydrogenase level \> 484 IU/L) could have an increased risk of hypercoagulable state and subsequent thromboembolic complications.