Blood Coagulation DisordersNCT00086476
Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles
An observational study of Blood Coagulation Disorders, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Read more about this study
- Who is it for?
- Ages 2 to 80 years
- Conditions the study is for
- Blood Coagulation Disorders
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2004to 13 Jun 2011
- 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 2 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- This protocol will include children and adults with a clinical diagnosis of GPS, HPS, isolated delta-SPD, combined alpha delta-SPD, Griscelli disease, Chediak Higashi syndrome, Wiskott Aldrich syndrome or Thrombocytopenia absent radius syndrome. Patients whose platelets exhibit abnormal intracellular vesicle morphology will also be eligible.
Who cannot join
- Patients younger than 2 years and older than 80 years will be excluded. Patients with severe thrombocytopenia (fewer than 20 times 10(12) platelets/L) will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Investigations of Megakaryocytes From Patients With Abnormal Platelet Vesicles
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi, Griscelli, Wiskott-Aldrich, and Thrombocytopenia Absent Radius syndromes. These disorders are models for the study of organelle formation in megakaryocytes and platelets. Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes. Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin (TPO). Such cultured human megakaryocytes, amplified from bone marrow-derived CD34+ stem cells, synthesize and store organellar proteins and produce functional platelets. In this protocol, we plan to obtain bone marrow aspirates from 40 children and adults (ages 2 to 80 years) with GPS, HPS, and related disorders. Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits. We will culture megakaryocytes from CD34+ stem cells isolated from bone marrow aspirates. Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells. Precautions will be taken to prevent the primary risk of the bone marrow aspiration, i.e., prolonged bleeding at the aspiration site. Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients. However, the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation.
Read the detailed description
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi, Griscelli, Wiskott-Aldrich, and Thrombocytopenia Absent Radius syndromes. These disorders are models for the study of organelle formation in megakaryocytes and platelets. Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes. Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin (TPO). Such cultured human megakaryocytes, amplified from bone marrow-derived CD34+ stem cells, synthesize and store organellar proteins and produce functional platelets. In this protocol, we plan to obtain bone marrow aspirates from 40 children and adults (ages 2 to 80 years) with GPS, HPS, and related disorders. Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits. We will culture megakaryocytes from CD34+ stem cells isolated from bone marrow aspirates. Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells. Precautions will be taken to prevent the primary risk of the bone marrow aspiration, i.e., prolonged bleeding at the aspiration site. Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients. However, the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation.
- Conditions
- Blood Coagulation Disorders
- Keywords
- Gray Platelet Syndrome, Hermansky-Pudlak Syndrome, Storage Pool Deficiency, Organelle Formation, Megakaryocyte Development, Megakaryocytes, Platelets, Dense Granules, Alpha Granules, Lysosome-related Organelles, GPS, HPS, Griscelli Disease, Chediak Higashi Syndrome, Wiskott Aldrich Syndrome, Platelet, Congenital Bleeding Disorders, SAC, Vesicle
- Medical subject headings
- Blood Coagulation Disorders, Gray Platelet Syndrome, Hermanski-Pudlak Syndrome, Platelet Storage Pool Deficiency, Chediak-Higashi Syndrome, Wiskott-Aldrich Syndrome, Blister
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2004 (estimated)
- Study start29 Jun 2004
- Study completion13 Jun 2011
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 Blood Coagulation DisordersStudies of the same condition, open and under way.
- 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00086476
- Sponsor's protocol ID
- 040226
- Other IDs
- 04-HG-0226
- Status last verified
- 13 Jun 2011
- First submitted
- 1 Jul 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets. 2001 Aug;12(5):261-73. doi: 10.1080/09537100120068170.
PubMed 11487378White JG. Ultrastructural studies of the gray platelet syndrome. Am J Pathol. 1979 May;95(2):445-62.
PubMed 453324McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res. 1999 Jul 1;95(1):1-18. doi: 10.1016/s0049-3848(99)00015-8.
PubMed 10403682
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigations of Megakaryocytes From Patients With Abnormal Platelet Vesicles
- ClinicalTrials.gov ID
- NCT00086476
- Acronym / sponsor ID
- 040226
- Conditions
- Blood Coagulation Disorders
- Keywords
- Gray Platelet Syndrome, Hermansky-Pudlak Syndrome, Storage Pool Deficiency, Organelle Formation, Megakaryocyte Development, Megakaryocytes, Platelets, Dense Granules
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 29 Jun 2004
- Study completion
- 13 Jun 2011
- First posted
- 2 Jul 2004 (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.
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi, Griscelli, Wiskott-Aldrich, and Thrombocytopenia Absent Radius syndromes. These disorders are models for the study of organelle formation in megakaryocytes and platelets. Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes. Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin (TPO). Such cultured human megakaryocytes, amplified from bone marrow-derived CD34+ stem cells, synthesize and store organellar proteins and produce functional platelets. In this protocol, we plan to obtain bone marrow aspirates from 40 children and adults (ages 2 to 80 years) with GPS, HPS, and related disorders. Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits. We will culture megakaryocytes from CD34+ stem cells isolated from bone marrow aspirates. Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells. Precautions will be taken to prevent the primary risk of the bone marrow aspiration, i.e., prolonged bleeding at the aspiration site. Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients. However, the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation.
Detailed description
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi, Griscelli, Wiskott-Aldrich, and Thrombocytopenia Absent Radius syndromes. These disorders are models for the study of organelle formation in megakaryocytes and platelets. Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes. Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin (TPO). Such cultured human megakaryocytes, amplified from bone marrow-derived CD34+ stem cells, synthesize and store organellar proteins and produce functional platelets. In this protocol, we plan to obtain bone marrow aspirates from 40 children and adults (ages 2 to 80 years) with GPS, HPS, and related disorders. Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits. We will culture megakaryocytes from CD34+ stem cells isolated from bone marrow aspirates. Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells. Precautions will be taken to prevent the primary risk of the bone marrow aspiration, i.e., prolonged bleeding at the aspiration site. Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients. However, the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation.
Study design
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- This protocol will include children and adults with a clinical diagnosis of GPS, HPS, isolated delta-SPD, combined alpha delta-SPD, Griscelli disease, Chediak Higashi syndrome, Wiskott Aldrich syndrome or Thrombocytopenia absent radius syndrome. Patients whose platelets exhibit abnormal intracellular vesicle morphology will also be eligible.
Key exclusion criteria (1 listed)
- Patients younger than 2 years and older than 80 years will be excluded. Patients with severe thrombocytopenia (fewer than 20 times 10(12) platelets/L) will be excluded.
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 2 Jul 2017.
- Background: PubMed 11487378Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets. 2001 Aug;12(5):261-73. doi: 10.1080/09537100120068170.
- Background: PubMed 453324White JG. Ultrastructural studies of the gray platelet syndrome. Am J Pathol. 1979 May;95(2):445-62.
- Background: PubMed 10403682McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res. 1999 Jul 1;95(1):1-18. doi: 10.1016/s0049-3848(99)00015-8.
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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 Blood Coagulation Disorders, run by National Human Genome Research Institute (NHGRI) 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 1 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 2 Jul 2017. 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 NCT00086476, 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 2 Jul 2017.