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Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease

NCT02972138 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 80

Last updated 2017-10-06

No results posted yet for this study

Summary

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75,000 individuals in the United States and almost 20,000- 25,000 subjects in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharian Africa to European countries. Studies of global burden disease have pointed out the invalidating impact of SCD on patient quality of life. This requires the development of new therapeutic options to treat sickle cell related acute and chronic complications. SCD is caused by a point mutation in the β-globin gene resulting in the synthesis of pathological hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density and further acceleration of HbS polymerization. Pathophysiological studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of SCD, in which intravascular sickling in capillaries and small vessels leads to vaso-occlusion and impaired blood flow with ischemic/reperfusion injury. In microcirculation, vaso-occlusive events (VOC) result from a complex and still partially known scenario, involving the interactions between different cell types, including dense red cells, reticulocytes, abnormally activated endothelial cells, leukocytes, platelets and plasma factors. Target organs, such as bone or lung, are involved in both acute and chronic clinical manifestations of SCD, related to their peculiar anatomic organization mainly characterized by sluggish circulation and relative local hypoxia. VOCs combined with marrow hyperplasia and inflammation has been suggested to contribute to the development of sickle bone disease (SBD). Recently, it has been proposed a possible role of vitamin D deficiency in SBD, which appears to be subordinated to the primary defect in bone homeostasis. In a humanized mouse model for SCD, we recently reported that SBD is due to imbalance between osteoblast/osteoclast activity induced by recurrent VOCs. In addition, we show that zoledronic acid prevents bone impairment related to SCD, reducing osteoclast activity and improving osteoblast performance.

Conditions

  • Sickle Cells Disease

Sponsors & Collaborators

  • Società Italiana Talassemie ed Emoglobinopatie

    lead OTHER

Principal Investigators

  • Luca G Dalle Carbonare, MD · Università degli studi di Verona

Eligibility

Min Age
18 Years
Max Age
50 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2010-01-31
Primary Completion
2015-12-31
Completion
2017-09-30

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02972138 on ClinicalTrials.gov