Molecular Biology of Polycythemia - Full Text View

Sponsors and Collaborators:	University of Utah National Institutes of Health (NIH)
Information provided by:	University of Utah
ClinicalTrials.gov Identifier:	NCT00722527

Purpose

The purpose of this project is to find a gene and its mutation that cause PFCP. When this is accomplished, new therapies to control and eventually cure the disease can be designed.

Condition
Primary Familial Congenital Polycythemia Increased Hemoglobin Concentrations

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, Prospective
Official Title:	Molecular Biology of Polycythemia

Further study details as provided by University of Utah:

Primary Outcome Measures:

Identify the molecular defect of a polycythemic disorder [ Time Frame: Weekly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Define disease causing lesions of the erythropoietin (EPO) and EPO receptor (EPOR) pathway, as well as test the hypothesis that the EPOR mutations can cause cardiovascular disease. [ Time Frame: Monthly ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Whole blood

Estimated Enrollment:	200
Study Start Date:	July 2006
Estimated Study Completion Date:	May 2011
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts
Affected Population Subjects with an elevated hemoglobin concentration and who are suspected to have congenital polycythemia.

Detailed Description:

The proposed research is designed to characterize the clinical picture and genetic pattern of Primary and Familial Polycythemia (PFCP). The overall objective of this proposal is to examine the mechanisms of control of erythropoiesis concentrating on those that, when disturbed, result in polycythemia.

We have described the disease entity of primary familial and congenital polycythemia (PFCP), which provides a convenient model for studies of alterations of the control of erythropoiesis. We will continue to define disease causing lesions of the erythropoietin (EPO) and EPO receptor (EPOR) pathway and will test the hypothesis that the EPOR mutations can cause cardiovascular disease. We will also test the hypothesis that the aberrations and/or dysregulation of factors other than EPO and EPOR can have an effect on control of erythrocyte production by uncovering the molecular defects leading to primary familial and congenital polycythemia (PFCP) and other congenital polycythemias.

Our hypothesis is that other genes than the EPOR mutations are causative of the PFCP. These will be sought for by genetic and cell biology means. The purpose of the study is to identify the molecular defect of a polycythemic disorder.

5-7 teaspoons of peripheral blood will be drawn on all study subjects. The subject will be encouraged to speak with family members and ask if they too would like to participate. Blood will be drawn from all affected, consenting individuals.

After DNA is obtained, linkage analysis and/or mutation analysis will be performed. Depending on the number of different mutations, the spectrum of disease severity and physiologic mechanisms causing the disease can then be evaluated and discovered. Once the genes and responsible mutations are found, affected patients and relatives will be analyzed for diagnosis.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Subjects who are suspected to have congenital polycythemia will be included in the study.

Criteria

Inclusion Criteria:

1. Subjects with an elevated hemoglobin concentration (>18 in males and >16 in females) and who are suspected to have congenital polycythemia will be included in the study.

Exclusion Criteria:

Subjects who have a known acquired cause of polycythemia (increased hemoglobin/hematocrit) such as people living in high altitudes (in excess of 14,000 feet)
Subjects with heart disease, left to right heart shunt, severe hypoxia or severe pulmonary disease will be excluded from this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722527

Contacts

Contact: Josef T Prchal, MD	801-581-4220	josef.prchal@hsc.utah.edu
Contact: Kim Hickman, BS	801-581-3707	kimberly.hickman@hsc.utah.edu

Locations

United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Josef T Prchal, MD 801-581-4220 josef.prchal@hsc.utah.edu
Contact: Kim Hickman, BS 801-581-3707 kimberly.hickman@hsc.utah.edu
Principal Investigator: Josef T Prchal, MD
Sub-Investigator: Charles Parker, MD
Sub-Investigator: Scott Samuelson, MD
Sub-Investigator: Neeraj Agarwal, MD
Sub-Investigator: Andrew Chen, MD
Sub-Investigator: Mohamed Salama, MD
Sub-Investigator: Archana Agarwal, MD
Sub-Investigator: Todd Kelley, MD

Sponsors and Collaborators

University of Utah

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Josef T. Prchal, MD

University of Utah

More Information

Publications:

Prchal JT, Gordeuk VR. The HIF2A gene in familial erythrocytosis. N Engl J Med. 2008 May 1;358(18):1966; author reply 1966-7. No abstract available.

Agarwal N, Mojica-Henshaw MP, Simmons ED, Hussey D, Ou CN, Prchal JT. Familial polycythemia caused by a novel mutation in the beta globin gene: essential role of P50 in evaluation of familial polycythemia. Int J Med Sci. 2007 Oct 4;4(4):232-6.

Percy MJ, Sanchez M, Swierczek S, McMullin MF, Mojica-Henshaw MP, Muckenthaler MU, Prchal JT, Hentze MW. Is congenital secondary erythrocytosis/polycythemia caused by activating mutations within the HIF-2 alpha iron-responsive element? Blood. 2007 Oct 1;110(7):2776-7. No abstract available.

Skoda R, Prchal JT. Lessons from familial myeloproliferative disorders. Semin Hematol. 2005 Oct;42(4):266-73. Review.

Gregg XT, Prchal JT. Recent advances in the molecular biology of congenital polycythemias and polycythemia vera. Curr Hematol Rep. 2005 May;4(3):238-42. Review.

Bento MC, Chang KT, Guan Y, Liu E, Caldas G, Gatti RA, Prchal JT. Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: five new Caucasian patients. Haematologica. 2005 Jan;90(1):128-9.

Jedlickova K, Stockton DW, Prchal JT. Possible primary familial and congenital polycythemia locus at 7q22.1-7q22.2. Blood Cells Mol Dis. 2003 Nov-Dec;31(3):327-31.

Responsible Party:	University of Utah ( Josef T. Prchal, MD )
Study ID Numbers:	17665, 5R01HL50077-13
Study First Received:	July 23, 2008
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00722527 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Utah:

Primary Familial and Congenital Polycythemia
Molecular Biology
Genetics
Erythropoiesis
EPOR mutation

Study placed in the following topic categories:

Polycythemia
Hematologic Diseases

Additional relevant MeSH terms:

Polycythemia
Hematologic Diseases

ClinicalTrials.gov processed this record on May 07, 2009