The Molecular Biology of Paroxysmal Nocturnal Hemoglobinu... | NCT00721864

Studies
The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT00721864

Sponsor

University of Utah

Status

Completed

Last Update Posted

Aug 9, 2011Estimated

Enrollment

10Actual

Phase

Not provided

Conditions

Hemoglobinuria, Paroxysmal

Interventions

Not provided

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
R01HL5077-12

Status Module

Record Verification Date

Aug 2011

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

May 2006

Primary Completion Date

Dec 2010Actual

Completion Date

Dec 2010Actual

First Submitted Date

Jul 23, 2008

First Submission Date that Met QC Criteria

Jul 23, 2008

First Posted Date

Jul 25, 2008Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Aug 5, 2011

Last Update Posted Date

Aug 9, 2011Estimated

Name	Class
National Institutes of Health (NIH)	NIH

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

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.

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

Retention

Enrollment

10Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Affected Population		Subjects suspected of having Paroxysmal Nocturnal Hemoglobinuria (PNH)

Interventions

Not provided

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies		After sample is obtained

Secondary Outcomes

Measure	Description	Time Frame
Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells		After sample is obtained
Analysis of PrP function in human long term hematopoietic stem cells		After sample is obtained

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Those not meeting the inclusion criteria

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

7 Years

Maximum Age

Not provided

Standard Ages

ChildAdultOlder Adult

Study Population

Patients with paroxysmal nocturnal hemoglobinuria (PNH)

Sampling Method

Non-Probability Sample

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Josef T Prchal, MD	University of Utah	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
University of Utah		Salt Lake City	Utah	84132	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
11260069	Background	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.
12543108	Background	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.

ID	Term
D006457	Hemoglobinuria, Paroxysmal
D034062	Insomnia, Fatal Familial

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases