Paroxysmal HemoglobinuriaNCT00039923
Transfer of GPI-Linked Proteins to Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria
An observational study of Paroxysmal Hemoglobinuria, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Paroxysmal Hemoglobinuria
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2002to Jun 2005
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The following must be met before the subject may be enrolled:
- PNH patients with group A(1) blood who require at least three units of red cells as judged by their primary care physician; criteria for transfusion would include hemoglobin below 7.5 g/dl or symptoms related to anemia (impaired exercise tolerance, angina, shortness of breath) that warrant therapy.
- A PNH clone of greater than 40% and not have been transfused with group O blood for at least three months previously.
- Eighteen years of age or older.
- Karnofsky performance status of 60% or better.
- Adequate organ function as defined by serum creatinine less than 2.0 mg/dl.
- Able to comprehend and willing to sign an informed consent.
Who cannot join
- Any one of the following eliminates a subject from participating:
- Evidence of uncontrolled infection.
- Known alloimmunization to red cell antigens.
- Treatment with investigational agent or hematopoietic growth factors within 4 weeks of study entry.
- Psychiatric, addictive or any disorder that compromises ability to give truly informed consent.
- Patients who are moribund or who have concurrent hepatic, renal, cardiac disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Study to Determine if Transfer of Gpi-Linked Proteins Occurs Following Transfusion of Red Cells to Patients With Paroxysmal Nocturnal Hemoglobinuria
This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion.
Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study.
Read more
Participants will come to the NIH Clinical Center for the following procedures:
- Interview about the severity of their anemia-related symptoms
- Blood test
- Blood transfusion, if required. Patients will be transfused with compatible group O blood. The donor blood will be washed (rinsed with a salt solution) until it is 99% free of donor plasma. Group O blood is given instead of group A1 in order to be able to distinguish the patient's cells from the transfused cells.
Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail.
If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.
Read the detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal bone marrow disorder, resulting from an acquired, somatic X-linked mutation of the PIG-A gene in an hematopoietic stem cell. Absence of PIG-A function in a cell prevents synthesis of the glycosylphosphatidylinositol (GPI) moiety, which anchors many different types of proteins to the cell membrane. Intravascular red cell destruction, the hallmark of the disorder, is caused by susceptibility of the abnormal erythrocyte to complement-mediated lysis; this sensitivity is due to lack of CD59, a potent inhibitor of the late components of complement and reactive lysis. In vitro studies from this laboratory have demonstrated transfer of GPI-linked proteins, CD55 and CD59, from normal to deficient cells and transfer is associated with resistance to hemolysis. Patients with PNH frequently require transfusion as their standard care. In addition, patients with all blood groups requiring transfusion will often receive compatible group O blood. Group O blood is prevalent in blood bank inventories; and red cell survival after transfusion is equal to that after transfusion of "in group" blood. The purpose of this study is to examine protein transfer of GPI-linked proteins from transfused cells to deficient cells obtained from patients with PNH. Patients with group A(1) blood will receive compatible group O blood so that donor and recipient blood cells can be discriminated. Flow cytometric studies will be performed subsequently to determine if transfer of GPI-linked protein to patients' cells has occurred.
- Conditions
- Paroxysmal Hemoglobinuria
- Keywords
- Hemolysis, CD55, CD59, Transfusion, Paroxysmal Nocturnal Hemoglobinuria, PNH
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Hemolysis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2002 (estimated)
- Study startJun 2002
- Study completionJun 2005
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 Paroxysmal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Enrolment
- 7 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00039923
- Sponsor's protocol ID
- 020227
- Other IDs
- 02-H-0227
- Status last verified
- Jun 2005
- First submitted
- 14 Jun 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Sloand EM, Maciejewski JP, Dunn D, Moss J, Brewer B, Kirby M, Young NS. Correction of the PNH defect by GPI-anchored protein transfer. Blood. 1998 Dec 1;92(11):4439-45.
PubMed 9834251Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood. 1990 Apr 15;75(8):1595-601. No abstract available.
PubMed 2183885Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell. 1997 Jan 10;88(1):1-4. doi: 10.1016/s0092-8674(00)81850-4. No abstract available.
PubMed 9019395
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Determine if Transfer of Gpi-Linked Proteins Occurs Following Transfusion of Red Cells to Patients With Paroxysmal Nocturnal Hemoglobinuria
- ClinicalTrials.gov ID
- NCT00039923
- Acronym / sponsor ID
- 020227
- Conditions
- Paroxysmal Hemoglobinuria
- Keywords
- Hemolysis, CD55, CD59, Transfusion, Paroxysmal Nocturnal Hemoglobinuria, PNH
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jun 2002
- Study completion
- Jun 2005
- First posted
- 17 Jun 2002 (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 will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion.
Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study.
Participants will come to the NIH Clinical Center for the following procedures:
- Interview about the severity of their anemia-related symptoms
- Blood test
- Blood transfusion, if required. Patients will be transfused with compatible group O blood. The donor blood will be washed (rinsed with a salt solution) until it is 99% free of donor plasma. Group O blood is given instead of group A1 in order to be able to distinguish the patient's cells from the transfused cells.
Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail.
If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.
Detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal bone marrow disorder, resulting from an acquired, somatic X-linked mutation of the PIG-A gene in an hematopoietic stem cell. Absence of PIG-A function in a cell prevents synthesis of the glycosylphosphatidylinositol (GPI) moiety, which anchors many different types of proteins to the cell membrane. Intravascular red cell destruction, the hallmark of the disorder, is caused by susceptibility of the abnormal erythrocyte to complement-mediated lysis; this sensitivity is due to lack of CD59, a potent inhibitor of the late components of complement and reactive lysis. In vitro studies from this laboratory have demonstrated transfer of GPI-linked proteins, CD55 and CD59, from normal to deficient cells and transfer is associated with resistance to hemolysis. Patients with PNH frequently require transfusion as their standard care. In addition, patients with all blood groups requiring transfusion will often receive compatible group O blood. Group O blood is prevalent in blood bank inventories; and red cell survival after transfusion is equal to that after transfusion of "in group" blood. The purpose of this study is to examine protein transfer of GPI-linked proteins from transfused cells to deficient cells obtained from patients with PNH. Patients with group A(1) blood will receive compatible group O blood so that donor and recipient blood cells can be discriminated. Flow cytometric studies will be performed subsequently to determine if transfer of GPI-linked protein to patients' cells has occurred.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- PNH patients with group A(1) blood who require at least three units of red cells as judged by their primary care physician; criteria for transfusion would include hemoglobin below 7.5 g/dl or symptoms related to anemia (impaired exercise tolerance, angina, shortness of breath) that warrant therapy.
- A PNH clone of greater than 40% and not have been transfused with group O blood for at least three months previously.
- Eighteen years of age or older.
- Karnofsky performance status of 60% or better.
- Adequate organ function as defined by serum creatinine less than 2.0 mg/dl.
Key exclusion criteria (6 listed)
- Evidence of uncontrolled infection.
- Known alloimmunization to red cell antigens.
- Treatment with investigational agent or hematopoietic growth factors within 4 weeks of study entry.
- Psychiatric, addictive or any disorder that compromises ability to give truly informed consent.
- Patients who are moribund or who have concurrent hepatic, renal, cardiac disease.
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
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 9834251Sloand EM, Maciejewski JP, Dunn D, Moss J, Brewer B, Kirby M, Young NS. Correction of the PNH defect by GPI-anchored protein transfer. Blood. 1998 Dec 1;92(11):4439-45.
- Background: PubMed 2183885Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood. 1990 Apr 15;75(8):1595-601. No abstract available.
- Background: PubMed 9019395Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell. 1997 Jan 10;88(1):1-4. doi: 10.1016/s0092-8674(00)81850-4. No abstract available.
Related trials for Paroxysmal Hemoglobinuria
Enrolling by invitationObservational study
An Observational Post-Authorization Safety and Effectiveness Study of Ravulizumab in Adult Patients Aged 18 and Older Diagnosed With Paroxysmal Nocturnal Hemoglobinuria Using Multicenter Electronic Medical Records in South Korea
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Paroxysmal Hemoglobinuria, run by National Heart, Lung, and Blood Institute (NHLBI) 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 7 inclusion and 6 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 4 Mar 2008. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00039923, 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 4 Mar 2008.