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The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00721864
Recruitment Status : Completed
First Posted : July 25, 2008
Last Update Posted : August 9, 2011
National Institutes of Health (NIH)
Information provided by:
University of Utah

Brief Summary:
This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.

Condition or disease
Hemoglobinuria, Paroxysmal

Detailed Description:

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, thrombosis, and variable cytopenia. It can be associated with significant morbidity including acute kidney failure, cerebral infarction, mesenteric infarction, Budd-Chiari syndrome, aplastic anemia, and leukemic transformation. The average survival time from diagnosis is 15 years.

PNH is an acquired clonal disorder of the hematopoietic stem cell. Two distinct populations of hematopoietic cells exist in each PNH patient: one non-clonal population of normal cells, and one clonal population of PNH cells. The clonal population of PNH cells is identified by a mutation in the PIG-A gene that results in absence of the glycophosphatidylinositol (GPI) anchor of several surface proteins. Consequently, these surface proteins are unable to perform their functions on the cell surface. Deficiency of two of these surface proteins, CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis) that prevent complement mediated destruction, have been shown to underlie the clinical presentation of PNH. Identifying the mutation causing the predominant clones may help us better understand the molecular biology of PNH. When this is accomplished, new therapies to control and eventually cure the disease can be designed.

In addition, we propose to determine the function of PrP in human hematopoietic stem cells. PrP is a glycoprotein attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In PNH, a disorder whose pathogenesis lies in the absence of GPI anchors, PrP expression is reduced in monocytes and granulocytes from the PNH clone.

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Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study Start Date : May 2006
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Affected Population
Subjects suspected of having Paroxysmal Nocturnal Hemoglobinuria (PNH)

Primary Outcome Measures :
  1. Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies [ Time Frame: After sample is obtained ]

Secondary Outcome Measures :
  1. Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells [ Time Frame: After sample is obtained ]
  2. Analysis of PrP function in human long term hematopoietic stem cells [ Time Frame: After sample is obtained ]

Biospecimen Retention:   Samples With DNA
Whole Blood

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with paroxysmal nocturnal hemoglobinuria (PNH)

Inclusion Criteria:

  1. Subjects suspected of or diagnosed with Paroxysmal Nocturnal Hemoglobinuria (PNH)
  2. Age > 7

Exclusion Criteria:

1. Those not meeting the inclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00721864

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United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
National Institutes of Health (NIH)
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Principal Investigator: Josef T Prchal, MD University of Utah

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Responsible Party: Josef T. Prchal, MD, University of Utah Identifier: NCT00721864    
Other Study ID Numbers: 17790
First Posted: July 25, 2008    Key Record Dates
Last Update Posted: August 9, 2011
Last Verified: August 2011
Keywords provided by University of Utah:
Paroxysmal Nocturnal Hemoglobinuria
PIG-A Mutation
Prion Protein
Hematopoietic stem cells
Clonal disorder
Additional relevant MeSH terms:
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Hemoglobinuria, Paroxysmal
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases