Hemoglobinuria, ParoxysmalNCT00721864
The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
An observational study of Hemoglobinuria, Paroxysmal, run by University of Utah at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Hemoglobinuria, Paroxysmal
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Dec 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with paroxysmal nocturnal hemoglobinuria (PNH)
Who may be able to join
- Subjects suspected of or diagnosed with Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Age > 7
Who cannot join
- 1. Those not meeting the inclusion criteria
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Hemoglobinuria, Paroxysmal
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, PIG-A Mutation, Prion Protein, Hematopoietic stem cells, Clonal disorder
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Insomnia, Fatal Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Affected Population | Subjects suspected of having Paroxysmal Nocturnal Hemoglobinuria (PNH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies
Measured: After sample is obtained
Secondary outcomes (2)
Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells
Measured: After sample is obtained
Analysis of PrP function in human long term hematopoietic stem cells
Measured: After sample is obtained
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2008 (estimated)
- Study startMay 2006
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemoglobinuria, ParoxysmalStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Josef T Prchal, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00721864
- Sponsor's protocol ID
- 17790
- Other IDs
- R01HL5077-12
- Status last verified
- Aug 2011
- First submitted
- 23 Jul 2008
- Last updated
- 9 Aug 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11260069Risitano 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.
PubMed 12543108Zhang 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.
PubMed 16467153
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- ClinicalTrials.gov ID
- NCT00721864
- Acronym / sponsor ID
- 17790
- Conditions
- Hemoglobinuria, Paroxysmal
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, PIG-A Mutation, Prion Protein, Hematopoietic stem cells, Clonal disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- May 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 25 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Affected Population | – | –Subjects suspected of having Paroxysmal Nocturnal Hemoglobinuria (PNH) |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with paroxysmal nocturnal hemoglobinuria (PNH)
Key inclusion criteria (2 listed)
- Subjects suspected of or diagnosed with Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Age > 7
Key exclusion criteria (1 listed)
- 1. Those not meeting the inclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies
Time frame: After sample is obtained
2 secondary outcomes
Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells
Time frame: After sample is obtained
Analysis of PrP function in human long term hematopoietic stem cells
Time frame: After sample is obtained
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2011.
- Background: PubMed 11260069Durig 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.
- Background: PubMed 12543108Risitano 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.
- Background: PubMed 16467153Zhang 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.
Related trials for Hemoglobinuria, Paroxysmal
Enrolling by invitationObservational study
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Hemoglobinuria, Paroxysmal
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Severe Aplastic Anemia, MDS (Myelodysplastic Syndrome)
RecruitingPhase 3
A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works
Paroxysmal Nocturnal Hemoglobinuria
Not yet recruitingPhase 3
A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
Paroxysmal Nocturnal Hemoglobinuria
RecruitingPhase 2
Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis
Severe Aplastic Anemia (SAA), Hypo-Plastic Myelodysplastic Syndrome (MDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josef T Prchal, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemoglobinuria, Paroxysmal, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies (time frame: After sample is obtained). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00721864, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2011.