Ongoing Research Studies

Research: A Vital Key to the Future

Many advances in the diagnosis, treatment and care of patients with bleeding disorders have occurred because of research studies called "clinical trials" or "protocols." There are many different kinds of clinical trials, including:

Studies that test new treatments, new combinations of drugs, or new approaches to treatments.
Prevention studies that look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning.
Diagnostic studies that are conducted to find better tests or procedures for diagnosing a particular disease or condition.
Screening studies to test the best way to detect certain diseases or health conditions.
Quality of Life studies that explore and measure ways to improve comfort and the quality of life for individuals with a chronic illness.
Surveillance studies that examine complications and outcomes related to certain diseases.

At the Hemophilia Center of Western Pennsylvania, we are currently recruiting patients to participate in the following studies:

Study Name	Description and Eligibility
Study of Von Willebrand Disease Genotype and Phenotype	The purpose of this multi-center study is to study the relationship between genetic defects of the VWF or related genes and the clinical impact on the diagnosis and management of their VWD bleeding disorder. The hypothesis is that most VWD is caused by a mutation in the VWF gene that causes reduced or abnormal VWF to be produced and this results in clinical bleeding and the diagnosis of VWD. The specific aims are: 1) Identify mutations in the VWF gene associated with type 1, type 2, or type 3 VWD and correlate these with a clinical bleeding assessment. 2) Determine the frequency low plasma VWF being caused by increased VWF clearance. Up to 3000 nationally and 500 locally, persons with the previous diagnosis of VWD and their families will be offered the opportunity of participating in this study that is directed at identifying VWF mutation (or other related genes) to the presence or absence of clinical relevant bleeding symptoms. We will also recruit and perform VWD testing on 20 healthy control subjects to control for sampling procedures and geographic differences.
Rituxan in Hemophilia A Inhibitor Patients	This study will examine the investigational drug rituximab. The study will determine if rituximab is effective and safe in decreasing the production of inhibitors in patients with severe congenital Hemophilia A. Qualifying patients will have 11 visits at the Hemophilia Center of Western Pennsylvania and 4 visits at the MUH-CTRC (Montefiore Clinical & Translational Research Center).
Universal Data and Serum Specimen Collection System for Hemophilia (UDC)	Patients with hemophilia or related disorders will be eligible to participate in this study, which could last from 5 - 10 years. The purpose of the study is to find how frequently individuals with hemophilia or related disorders have complications of their disease, such as joint damage, complications of their treatment, hepatitis, human immunodeficiency virus (HIV), and other viruses. Patients' medical records will be reviewed and recorded for research purposes. Additionally, a blood sample will be taken. Subjects will be told the results of their blood tests and a portion of the blood will be sent to the Centers for Disease Control for future research.
HCWP/ITxM Hemostasis and Thrombosis Research Registry (HCWP)	This project entails the development of a Center of Excellence in Hemostasisand Thrombosis Research Registry. The objectives of the study include identifying and obtaining permission of patients who may be eligible for participation in future research projects, and completing retrospective research studies.
Solid Organ Transplantation in HIV	This is a prospective Phase I multicenter study to evaluate the safety of solid organ transplantation in the setting of HIV infection. Although the organ transplantation itself is not experimental, the use of antiretroviral therapy in combination with anti-rejection immunosuppressive therapy is experimental. This study will evaluate the potential for toxicity, drug interactions, and potential for opportunistic infections, and stability of CD4 and HIV viral load following solid organ transplantation. The specific aims are 1) to evaluate the impact of liver transplantation, and post-transplant immunosuppression on HIV disease progression and markers of immune function and activity; 2) To evaluate the impact of HIV infection on graft function and survival; and 3) To describe the pharmacokinetic interactions between immunosuppressive agents and the hepatically metabolized antiretroviral (ARV) agents. A total of 275 subjects, including 125 liver transplant and 150 kidney transplant recipients, from 17 or more centers will be enrolled over 5 years, with 3-year follow-up per patient.
IL-11 in Menorrhagia	This study recruits women between the ages of 18 and 45 with a diagnosis of type 1 Von Willebrand disease with menorrhagia (heavy monthly periods). The purpose of this study is to determine the safety and effectiveness of the drug Neumega® (rhIL-11). The study will also examine if Neumega® reduces blood loss during periods. A total of 10-15 research subjects are needed to complete the 6-month study. After a screening visit at the HCWP, subjects will have 4 short consecutive visits to an outpatient study center, followed by 6 monthly visits to HCWP. Subjects will be trained to give Neumega® injections (shots), will keep a home diary of their periods, agree not to become pregnant, have no history of heart disease, and be willing to have blood drawn.
IL-11 in Surgery	This study recruits men and women over 18, with a diagnosis of type 1 Von Willebrand disease who are planning to undergo elective surgery. The purpose of this study is to determine the safety and effectiveness of the drug Neumega® (rhIL-11) in reducing and preventing post-surgical bleeding. Subjects will receive one Neumega® injection daily for 6-7 days. A total of 10-15 research subjects are needed to complete the 4-week study. After a screening visit at HCWP, subjects will have 4 short consecutive visits to an outpatient study center and upon admission to hospital for elective surgery, will be visited by the study doctor and/or nurse daily. A final visit will be done at the HCWP. Subjects will keep a home diary, agree not to conceive children, have no history of heart disease and be willing to have blood drawn.
Gene Transfer of Factor IX in Adeno Associated Virus with Immunosuppression:	This research study will help determine the safety of a new type of investigational approach called “gene transfer” in subjects with severe hemophilia B. Hemophilia B is caused by a defect in the gene that produces the factor IX protein. Factor IX protein is important in blood clotting. Patients with severe hemophilia B have less than 1% of the normal clotting factor IX. Such low levels can result in spontaneous bleeding episodes that cause destruction of bone and tissue. Since the factor IX gene was discovered,scientists have been working on ways to transfer the normal factor IX gene into hemophilia B patients' cells to cause their cells to produce normal factor IX protein. The agents used to bring a gene inside cells are called “vectors”. The gene transfer may offer a way to raise levels of factor IX protein in the circulation, and stop or reduce the spontaneous bleeding episodes. This study involves gene transfer of the factor IX gene by a viral vector (the adeno-associated virus [AAV]) into the liver. The procedure using gene transfer is experimental. In the past, eight subjects with hemophilia B have received AAV vector in the muscle for a hemophilia B trial by intramuscular injection (a shot). Seven subjects with hemophilia B have received AAV vector in the earlier version of this hemophilia B liver trial. Male subjects with severe hemophilia B, 18 years of age, without inhibitors, severe liver or kidney disease may be eligible to participate. The study involves at least 26 research visits, testing, and blood draws, and includes a 2-4 day hospital stay. Additionally, subjects will receive 2 immunosuppressive drugs during the time before and after the gene transfer. The total enrollment for this study will be up to 9 subjects and follow up will last 15 years. The University of Pittsburgh is one of three sites offering this study.
SPINART	This pharmaceutically sponsored research study is for subjects with Hemophilia A. Hemophilia A is a disease in which the body is unable to make the blood protein called factor VIII. Factor VIII is required for blood clotting. The study will help determine the effects of two Factor VIII (Kogenate ® FS) dosing regimens on overall joint health, bleeding events and quality of life. Subjects between the ages of 20 and 50, and have more than 150 exposure days to FVIII, and have for most of their lifetime been treating on an “On-Demand” basis (meaning treating bleeding incidents once they have occurred) may be eligible to participate. The study involves 9 visits, 2 sets of MRI’s, blood draws and questionnaires and testing. The HCWP hopes to recruit 2-4 subjects. At least 80 subjects (participants) at all sites will be included in this study. The study will be conducted in approximately 35 centers in the United States, Canada, Israel and Poland. Participation will last approximately 3 years.
International ITI	This study is a multicenter, international prospective study comparing two doses of factor VIII immune tolerance in children age 7 or younger with hemophilia A who have inhibitors. Hemophilia A is an X-linked disorder of coagulation factor VIII (which helps blood to clot), which can result in spontaneous and traumatic bleeding or hemorrhages. Inhibitors are antibodies which form to infused factor VIII (because the immune system sees it as “foreign”). Inhibitors prevent clotting factor from working properly and make treatment difficult. The study will require all subjects to have an inhibitor titer (anti-VIII less than 10 Bethesda Units B.U.) by avoiding factor VIII concentrate for up to 24 months, and using alternative treatments, FEIBA or VIIa as standard of care. Once the inhibitor falls to less than 10 B.U., measured on two occasions, subjects will then be randomized to low-dose (50 IU/kg three times weekly) or high-dose (200 IU/kg daily) immune tolerance (ITI). All doses are infused by single IV infusion. Ports may be used for administration. Subjects may be eligible for study of they are 7 years old and younger with severe hemophilia A, and if their inhibitor level to factor VIII between 5 B.U. and 200 B.U. A total of 150 subjects will be enrolled at U.S. and European sites, and 1-3 at HCWP. The study requires at least monthly visits and numerous blood draws. This study will provide helpful information for treatment of patients. Among the information collected will be time to immune tolerance, cost, and hemophilia genotype information, which may help predict response to immune tolerance. The study is expected to last up to 3 years per patient, and up to 10 years overall.
Baxter rVWF	This study is for subjects 18 to 60 years of age with type 3 von Willebrand disease(VWD). The Hemophilia Center of Western PA is one of many sites which hope to enroll 31 subjects worldwide. The study will test the safety and tolerability of a new drug called recombinant von Willebrand factor (VWF:RCo). The drug will be given by intravenous infusion (through a vein in the arm) at different dose levels to test safety. These include a single dose at 2 IU/kg; a single dose at 7.5 IU/kg; a single dose at 20 IU/kg; and a single dose at 50 IU/kg. There will be 30 total subjects studied, two at the lowest dose, five each at the middle doses, and eighteen at the highest dose. Subjects in the highest dose group will also receive standard recombinant VWF (Humate-P) about a week later, to compare findings. Study visits will occur at HCWP, and infusion of the study drug at Montefiore University Hospital (The Clinical and Translational Research Center (MUH-CTRC)). The study takes about seven to nine weeks per patient.
Genotype & AAV Vector Registry	This research study will assess genetic type of hemophilia (genotype) and evidence of exposure to AAV virus in those with hemophilia A or B who are at least 18 years of age. These are one time blood samples and will be drawn at HCWP. The results may be helpful for future gene therapy studies or future studies of new agents as they may help predict response to new treatments or gene therapy. We hope to enroll 250 subjects.
VWD BS in Children	This study involves studying bleeding and laboratory findings in children with von Willebrand disease (VWD) at HCWP. Charts will be reviewed following parental consent. The information gathered will be de-identified (name and person information removed) and will be compared to information from children without VWD at Children's Hospital of Pittsburgh. The study, which will last two years will help to determine bleeding predictors in children with VWD. If successful, the findings could help reduce bleeding complications by earlier diagnosis, earlier treatment and improve patient's quality of life. At least seven other sites in the United States will also participate.
IL-11 DDAVP Unresponsive Study	This is a study of the FDA-approved drug called recombinant interleukin-11 (rhIL-11, or Neumega®(174) raised levels of von Willebrand factor. The study involves two visits at HCWP and four visits to receive Neumega at Montefiore University Hospital-Clinical and Translational Research Center (MUH-CTRC). The study will monitor safety as well as effectiveness by lab tests. The HCWP hopes to recruit ten(10) participants. The study will last up to one(1) month per subject, and twenty-four(24) months for the entire study.

To learn more about HCWP Research studies and clinical trials, 412-209-7280, option 5.