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Clinical Trials: Blood - Sickle Cell Disease
IRB No. 13-061-6 (Dr. Biree Andemariam, PI): CASIRE Sickle Cell Renal Disease Cohort International Study Protocol
Study description not available
IRB No. 14-107-6 (Dr. Biree Andemariam, PI): Identification of Patient-specific RBC-endothelial Cell Adhesion Profiles as Markers of Sickle Cell Disease Severity.
The research objective of this proposal is to determine in 25 adult/pediatric SCD patients (1) the relationship between pain severity phenotype and the strength of adhesion between single red blood cells (RBCs) and single endothelial cells (ECs) isolated from peripheral blood and (2) the ex vivo effect of pharmacologic inhibitors on RBC-EC adhesion, creating both a patient-specific adhesion profile and therapeutic signature. The results are expected to lead to novel individually-targeted approaches to inhibit the onset and limit the duration of painful vaso-occlusive episodes (VOEs). Our central hypothesis is that the strength of adhesion between RBCs and ECs at baseline is related to patient-specific pain severity phenotype, resulting in the need for patient-specific drug therapy. To test the hypothesis, we will pursue the following three specific aims: Investigate the relationship between pain severity phenotype and baseline RBC-EC adhesion profile in SCD subjects – We will measure the strength of adhesion between single RBCs-ECs from SCD subjects at baseline. Baseline/steady-state adhesion profiles will be compared on an inter-patient level to determine which adhesion profiles correlate most highly with pain severity phenotype. Assess the association of VOE severity with changes in RBC-EC adhesion from baseline to VOE onset. We will measure the change in strength of adhesion between single RBCs-ECs from baseline to VOE onset. Changes in adhesion will be compared on an inter-patient level to determine whether relative changes in adhesion profile at VOE onset correlate with VOE severity. Test the ex vivo effect of targeted pharmacotherapy on the RBC-EC adhesion profile of SCD subjects – We will measure (at baseline and at VOE onset) the ex vivo inhibitory effect of two known RBC-EC adhesion blockers (propranolol and abciximab) to identify patient-specific anti-adhesive therapeutic signatures.
IRB No. 14-129-6 (Dr. Biree Andemariam, PI): Sickle Cell Trait-related Blood Cell Adhesion as a Determinant of Disparate Cancer Treatment Outcomes
SPECIFIC AIMS The research objective of this proposal is to determine if blood cells from persons who are sickle cell trait carriers react adversely to standard chemotherapy compared to blood cells from persons without this genotype. African-American women have disparate breast cancer survival rates compared to white women that cannot be fully explained by either socio-economic or tumor marker expression differences. While sickle cell trait (SCT) is rare in the white population, nearly 10% of African-Americans carry SCT and most are unaware. Several case reports in the literature have described adverse reactions to systemically administered chemotherapy in African-Americans with SCT raising the possibility that chemotherapy-induced intravascular sickling may occur. Subsequent vaso-occlusion (overt or sub-clinical) may give rise to symptoms such as pain and nausea, or clinical signs such as unexplained anemia and renal insufficiency. These signs and symptoms may lead to treatment delays, dose-reductions and in some cases, cessation of therapy altogether--- all of which can impact efficacy and, most importantly, survival. We have previously shown that red blood cells (RBCs) from individuals with SCT are more adhesive to vascular endothelium than normal RBCs and that this adhesion is enhanced under physiologic stress conditions. We aim to compare the effect of chemotherapy on RBC adhesion to endothelial proteins in white women and in African-American women with and without SCT. The results are expected to lead to novel approaches to reverse disparities in cancer treatment outcomes among African-Americans. Our central hypothesis is that RBCs from African-American women with SCT are more adherent to vascular endothelium in the presence of chemotherapy than are healthy RBCs from both white and African-American women without SCT. To test the hypothesis, we will pursue the following two specific aims: Assess for baseline differences in RBC adhesion to endothelial proteins among white women as compared to African-American women– We will measure the change in quantity and strength of adhesive interactions between single RBCs and endothelial proteins. The influence of race and SCT-status will be examined. Test the in vitro effect of chemotherapy on RBC adhesion to endothelial proteins among white women as compared to African-American women – We will measure the in vitro effect of chemotherapy on single RBC adhesion to endothelial proteins. The influence of race and SCT-status will be examined.
IRB No. 14-136-6 (Dr. Biree Andemariam, PI): Hemoglobinopathies and Bone Health
This research study has two purposes. The first purpose is to determine whether having sickle cell trait is a risk factor for the development of bone thinning at an earlier age than expected. Nearly 10% of African Americans carry sickle cell trait and most of them are unaware of it. African Americans are less likely to develop thin bones than whites, but if they sustain a bone fracture, they are more likely to die from it. We believe having sickle cell trait may lead to bone thinning and predispose a subset of African Americans to dangerously thin bones. The second purpose is to try to understand why individuals with sickle cell disease have thinner bones than healthy individuals do. Doctors have already discovered that people with sickle cell disease have very thin bones, but they have not determined why. Our study will try to identify whether the bone thinning is from the body not making enough bone or from the body losing bone once it is made.
IRB No. 16-210-6 (Dr. Biree Andemariam, PI): 3D Microscopic Imaging to Differentiate Healthy vs Diseased Red Blood Cells
This study is a prospective, clinical/translational research study using peripheral blood from consenting SCD patients and healthy control volunteers. From our earlier experiments with red blood cells using the 3D microscope, we have found that the mechanics of cell membrane fluctuations are very sensitive to the state of health of the cell. Parameters extracted from the dynamic imaging of the cell (amplitude of cell membrane fluctuation, frequency of cell membrane fluctuation, volume fluctuation and dynamic light scattering) can be used to discriminate healthy and diseased cells. The present study is aimed at collecting dynamic information of healthy versus diseased cells to quantify mechanical properties and estimate the state of health of the cells as well as the effectiveness of the developed 3D microscope in automatic identification of diseases. We hypothesize that the 3D microscope will be able to discriminate between healthy and sickle cell disease red blood cells, a tool that will have practical use in diagnosis and treatment of the disease. We will enroll both healthy and sickle cell disease adults who are 18 years of age and older who have not had a transfusion in the past 3 months.