The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT ID: NCT00721864

Last Updated: 2011-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

10 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-05-31

Study Completion Date

2010-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hemoglobinuria, Paroxysmal

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Affected Population

Subjects suspected of having Paroxysmal Nocturnal Hemoglobinuria (PNH)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

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

7 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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University of Utah

Principal Investigators

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Josef T Prchal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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Durig J, Giese A, Schmucker U, Kretzschmar HA, Duhrsen 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. doi: 10.1046/j.1365-2141.2001.02602.x.

Reference Type BACKGROUND
PMID: 11260069 (View on PubMed)

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. doi: 10.1016/s0301-472x(02)01011-1.

Reference Type BACKGROUND
PMID: 12543108 (View on PubMed)

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. doi: 10.1073/pnas.0510577103. Epub 2006 Feb 7.

Reference Type BACKGROUND
PMID: 16467153 (View on PubMed)

Other Identifiers

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R01HL5077-12

Identifier Type: -

Identifier Source: secondary_id

17790

Identifier Type: -

Identifier Source: org_study_id

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