Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00007150
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2000-12-09
Brief Title:
Treatment of Hemochromatosis
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Studies of Phlebotomy Therapy in Hereditary Hemochromatosis
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02-22
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the effectiveness of a test called MCV in guiding phlebotomy blood drawing therapy in patients with hemochromatosis an inherited disorder that causes too much iron to be absorbed by the intestine The excess damages body tissues most severely in the liver heart pancreas and joints Because iron is carried in the hemoglobin of red blood cells removing blood can effectively lower the body s iron stores
Patients with hemochromatosis undergo weekly phlebotomy treatments 1 pint per session to deplete iron stores This usually requires 10 to 50 treatments after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients This study will compare the usefulness of the ferritin test with that of MCV which measures red blood cell size in guiding phlebotomy therapy In addition the study will 1 examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients and 2 design a system for making blood collected from hemochromatosis donors available for transfusion into other patients
Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study Candidates will have a history physical evaluation review of medical records and blood tests and complete a symptoms questionnaire Participants will have the following procedures
Phlebotomy therapy every 1 to 2 weeks depending on iron levels
Blood sample collection for blood cell counts and iron studies at every phlebotomy session
Blood sample collection about 2 tablespoons every 1 to 2 weeks after iron stores have been depleted
Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron
With each blood donation that will be made available for transfusion to other patients participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors These include screening for the HIV and hepatitis viruses and for syphilis
Patients who meet height and weight requirements may be asked to consider double red cell donations using apheresis In this procedure whole blood is collected through a needle placed in an arm vein similar to routine phlebotomy The blood then circulates through a machine that separates it into its components The red cells are removed and the rest of the blood is returned to the body either through the same needle or through a second needle in the other arm Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy If cirrhosis is found the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved Patients with arthritis will be offered evaluation by the NIH Arthritis Service and depending on symptoms may be advised to have X-ray studies or a joint biopsy
Patients with hemochromatosis undergo weekly phlebotomy treatments 1 pint per session to deplete iron stores This usually requires 10 to 50 treatments after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients This study will compare the usefulness of the ferritin test with that of MCV which measures red blood cell size in guiding phlebotomy therapy In addition the study will 1 examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients and 2 design a system for making blood collected from hemochromatosis donors available for transfusion into other patients
Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study Candidates will have a history physical evaluation review of medical records and blood tests and complete a symptoms questionnaire Participants will have the following procedures
Phlebotomy therapy every 1 to 2 weeks depending on iron levels
Blood sample collection for blood cell counts and iron studies at every phlebotomy session
Blood sample collection about 2 tablespoons every 1 to 2 weeks after iron stores have been depleted
Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron
With each blood donation that will be made available for transfusion to other patients participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors These include screening for the HIV and hepatitis viruses and for syphilis
Patients who meet height and weight requirements may be asked to consider double red cell donations using apheresis In this procedure whole blood is collected through a needle placed in an arm vein similar to routine phlebotomy The blood then circulates through a machine that separates it into its components The red cells are removed and the rest of the blood is returned to the body either through the same needle or through a second needle in the other arm Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy If cirrhosis is found the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved Patients with arthritis will be offered evaluation by the NIH Arthritis Service and depending on symptoms may be advised to have X-ray studies or a joint biopsy
Detailed Description:
Hereditary hemochromatosis HH occurs in 1 in every 200-250 individuals of northern European descent and is the most common inherited disease in this population Although the molecular pathophysiology remains incompletely understood a homozygous mutation in the HFE gene Cys282Tyr is observed in nearly 100 of clinically confirmed cases The clinical manifestations of HH are due to inappropriately increased iron absorption with excessive iron deposition in the liver heart endocrine organs and joints
Phlebotomy treatment with removal of iron contained in the hemoglobin of red cells is the only effective therapy for HH Phlebotomy therapy relieves many of the symptoms of iron-mediated tissue damage and prevents progression to cirrhosis However published laboratory guidelines for monitoring phlebotomy therapy are based on retrospective data and in general allow a moderate level of iron overload to persist during maintenance therapy Since 1987 the DTM has piloted the use of the red cell mean corpuscular volume MCV in conjunction with the hemoglobin as a prospective guide to phlebotomy therapy in a small cohort of HH patients In contrast to other retrospectively-derived guidelines this simple inexpensive physiologic method was found to be a precise indicator of iron-limited erythropoiesis and could be easily applied to adjust the pace of phlebotomy and prevent excess iron reaccumulation
Although the majority of persons with HH meet eligibility criteria for allogeneic blood donation until recently regulatory guidelines restricted the use of therapeutically withdrawn blood for transfusion New regulations now permit increased flexibility in the use of such units for this purpose The purposes of this protocol are 1 to prospectively study the genotypic and phenotypic response to phlebotomy therapy in HH patients using the MCVhemoglobin monitoring guide and to validate the use of this guide in a large study cohort 2 to evaluate the course of severe hepatic disease and rheumatologic symptoms following sustained iron depletion and 3 to establish the safety and efficacy and document the operational issues inherent in a program to collect therapeutically withdrawn blood for use in allogeneic transfusion These goals have as their combined target the establishment of the simplest safest system for donor processing phlebotomy management and transfusion of blood drawn from HH subjects
Phlebotomy treatment with removal of iron contained in the hemoglobin of red cells is the only effective therapy for HH Phlebotomy therapy relieves many of the symptoms of iron-mediated tissue damage and prevents progression to cirrhosis However published laboratory guidelines for monitoring phlebotomy therapy are based on retrospective data and in general allow a moderate level of iron overload to persist during maintenance therapy Since 1987 the DTM has piloted the use of the red cell mean corpuscular volume MCV in conjunction with the hemoglobin as a prospective guide to phlebotomy therapy in a small cohort of HH patients In contrast to other retrospectively-derived guidelines this simple inexpensive physiologic method was found to be a precise indicator of iron-limited erythropoiesis and could be easily applied to adjust the pace of phlebotomy and prevent excess iron reaccumulation
Although the majority of persons with HH meet eligibility criteria for allogeneic blood donation until recently regulatory guidelines restricted the use of therapeutically withdrawn blood for transfusion New regulations now permit increased flexibility in the use of such units for this purpose The purposes of this protocol are 1 to prospectively study the genotypic and phenotypic response to phlebotomy therapy in HH patients using the MCVhemoglobin monitoring guide and to validate the use of this guide in a large study cohort 2 to evaluate the course of severe hepatic disease and rheumatologic symptoms following sustained iron depletion and 3 to establish the safety and efficacy and document the operational issues inherent in a program to collect therapeutically withdrawn blood for use in allogeneic transfusion These goals have as their combined target the establishment of the simplest safest system for donor processing phlebotomy management and transfusion of blood drawn from HH subjects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-CC-0045 | None | None | None |