Research Studies

Dr. Tammuella Chrisentery-Singleton is an Assistant Professor of Clinical Pediatrics at Tulane University and is board certified in pediatric hematology/oncology. She will receive training under the mentorship of Cindy Leissinger, MD, Chief, Section of Hematology & Medical Oncology at Tulane University School of Medicine and Director of the Louisiana Center for Bleeding and Clotting Disorders. Chrisentery-Singleton graduated with honors from Xavier University, received her MD from Louisiana State University and then completed her pediatric residency at the University of Miami. Following residency, she completed pediatric hematology/oncology fellowship training at Johns Hopkins University, where she worked with Dr. Jim Cassella and developed a serious interest in disorders of coagulation, particularly hemophilia. After her fellowship training, she was recruited to join the pediatric hematology/oncology faculty at LSU and Children's Hospital of New Orleans. In 2010, Chrisentery-Singleton accepted a position at Tulane University because of her desire to receive more training and spend more time in the specialized coagulation medicine program. As an NHF-Baxter Clinical Fellow, she will receive dedicated training in bleeding and clotting disorders for both children and adult patients, along with mentoring in clinical research related to bleeding disorders. She will also continue her work on several ongoing clinical trials, and pursue her project in developing models to better determine pharmacokinetic parameters with a minimal number of needle sticks in pediatric patients with hemophilia. Her goals are to steadily improve her knowledge and skills in caring for patients with coagulation disorders, and continue building her academic career in coagulation medicine.

In the long-term, Dr. Ivanciu's goals include the establishment of an independent research laboratory to focus on better understanding the pathological consequences of disruptions in the hemostatic balance. She believes that, as a past JGP Fellow, she is in a unique position to make meaningful contributions to the field of hematology and possibly help advance new therapies for the treatment of hemophilia.

Objective:

A novel recombinant coagulation factor VIII, rVIII-SingleChain, produced without added animal- or human-derived materials, is currently in a clinical phase I/III program (AFFINITY). The present non-clinical studies were conducted to investigate the pharmacokinetic (PK) profile of rVIII-SingleChain in animals to support assessment of its PK/pharmacodynamic properties for future clinical use.

Methods:

The PK behavior of rVIII-SingleChain was explored in hemophilia A mice, rats, and monkeys. Intravenous doses of 50-250 IU/kg for rVIII-SingleChain or a marketed full-length rFVIII concentrate were given. Systemic FVIII activity or antigen levels were recorded in plasma samples after injection. A thrombin generation assay was conducted to assess coagulation parameters ex vivo after treatment of hemophilia A mice with 250 IU/kg of rVIII- SingleChain or full-length rFVIII.

Summary:

In all animal species, treatment resulted in improved PK properties for rVIII- SingleChain compared to full-length rFVIII. Increased systemic availability and mean residence time were observed for rVIII-SingleChain. Correspondingly, the clearance rate was decreased and the terminal half-life was enhanced in comparison with full-length rFVIII. In vivo recovery and volume of distribution of rVIII-SingleChain were equivalent to full-length rFVIII. Consistent with the PK characteristics, rVIII-SingleChain showed a more favorable thrombin generation potential compared to full-length rFVIII between 2-6 days after treatment of FVIII-deficient mice. Results obtained showed that thrombin peak levels were kept between 50-250 nM for an increased period of time by rVIII-SingleChain compared to full-length rFVIII, with an average extension of 20 hours.

Conclusions:

The current investigations demonstrated favorable PK properties of rVIII- SingleChain in animal species. The presented results support the evidence necessary for conducting human trials to explore whether such favorable non-clinical PK characteristics may translate into clinical benefit.

This study explores perceptions among adolescent aged patients with inherited bleeding disorders regarding religiosity/spirituality and whether their beliefs have an impact on the pain they experience. Subjects participating will be assessed in regards to the type, frequency and intensity of pain experienced and measures used to cope with the pain. Finally, we will measure patient self reports of disease self efficacy. To further assess the impact of religiosity/spirituality on the family system, we will be measuring parental perceptions of religiosity/spirituality with parents of the participating adolescents.