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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00721864
Other study ID # 17790
Secondary ID R01HL5077-12
Status Completed
Phase N/A
First received July 23, 2008
Last updated August 5, 2011
Start date May 2006
Est. completion date December 2010

Study information

Verified date August 2011
Source University of Utah
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date December 2010
Est. primary completion date December 2010
Accepts healthy volunteers No
Gender Both
Age group 7 Years and older
Eligibility 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective


Related Conditions & MeSH terms


Locations

Country Name City State
United States University of Utah Salt Lake City Utah

Sponsors (2)

Lead Sponsor Collaborator
University of Utah National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Dürig J, Giese A, Schmücker U, Kretzschmar HA, Dührsen U. Decreased prion protein expression in human peripheral blood leucocytes from patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2001 Mar;112(3):658-62. — View Citation

Risitano AM, Holada K, Chen G, Simak J, Vostal JG, Young NS, Maciejewski JP. CD34+ cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of cellular prion protein (PrPc). Exp Hematol. 2003 Jan;31(1):65-72. — View Citation

Zhang CC, Steele AD, Lindquist S, Lodish HF. Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2184-9. Epub 2006 Feb 7. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies After sample is obtained No
Secondary Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells After sample is obtained No
Secondary Analysis of PrP function in human long term hematopoietic stem cells After sample is obtained No
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