HemochromatosisPhase 2NCT00007150
Treatment of Hemochromatosis
A Phase 2 study testing Phlebotomy in people with Hemochromatosis, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hemochromatosis
- What is being tested?
- Phlebotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 622 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2001to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. Up to 50 percent of the total study population may have received prior phlebotomy therapy.
- Elevated transferrin saturation and/or ferritin level, but diagnosis of HH not yet confirmed by genotype or liver biopsy.
- Elevated transferrin saturation and/or ferritin level without genotype findings listed above, but with elevated hepatic iron index on liver biopsy.
- Family member screening (unknown HH phenotype or genotype)
Who cannot join
- Age less than 15 years.
- Pregnancy.
- Patients requiring therapeutic phlebotomy for reasons other than iron overload (polycythemia vera).
- Patients with iron overload not due to HH (e.g. hepatitis C infection, porphyria cutanea tarda, Wilson s disease, alpha-1-antitrypsin deficiency, alcohol abuse).
- Other medical illness or condition which, in the opinion of the Investigators, may contraindicate participation due to risk to patient or to Donor Center.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Studies of Phlebotomy Therapy in Hereditary Hemochromatosis
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.
Read more
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.
Read the 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 MCV/hemoglobin 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.
- Conditions
- Hemochromatosis
- Being tested
- Phlebotomy
- Keywords
- Phlebotomy Therapy, Hemochromatosis, Iron Overload, Hereditary Hemochromatosis, Blood Donation
- Medical subject headings
- Hemochromatosis, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhlebotomyProcedure or surgery
Therapeutic phlebotomy, the periodic, frequent removal of the iron contained in the hemoglobin of red blood cells.
| Study group | Role | What they receive |
|---|---|---|
| 1/HH patients | Other | HH patients Receives: Procedure: Phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
MCV drops 1-3% below baseline
Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion
Measured: 4 to 12 months after starting phlebotomy therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2000 (estimated)
- Study start1 Jan 2001
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HemochromatosisStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 622 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Leonard N Chen, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007150
- Sponsor's protocol ID
- 010045
- Other IDs
- 01-CC-0045
- Status last verified
- 6 Feb 2026
- First submitted
- 9 Dec 2000
- Last updated
- 16 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lucotte G. Celtic origin of the C282Y mutation of hemochromatosis. Blood Cells Mol Dis. 1998 Dec;24(4):433-8. doi: 10.1006/bcmd.1998.0212.
PubMed 9851897Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, Schatzman RC. The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem. 1997 May 30;272(22):14025-8. doi: 10.1074/jbc.272.22.14025.
PubMed 9162021Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996 Aug;13(4):399-408. doi: 10.1038/ng0896-399.
PubMed 8696333Leitman SF, Browning JN, Yau YY, Mason G, Klein HG, Conry-Cantilena C, Bolan CD. Hemochromatosis subjects as allogeneic blood donors: a prospective study. Transfusion. 2003 Nov;43(11):1538-44. doi: 10.1046/j.1537-2995.2003.00570.x.
PubMed 14617312Wang X, Mendelsohn L, Rogers H, Leitman S, Raghavachari N, Yang Y, Yau YY, Tallack M, Perkins A, Taylor JG 6th, Noguchi CT, Kato GJ. Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Kruppel-like factor. Blood. 2014 Aug 7;124(6):946-54. doi: 10.1182/blood-2013-11-539718. Epub 2014 Jun 10.
PubMed 24916507
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Phlebotomy Therapy in Hereditary Hemochromatosis
- ClinicalTrials.gov ID
- NCT00007150
- Acronym / sponsor ID
- 010045
- Conditions
- Hemochromatosis
- Keywords
- Phlebotomy Therapy, Hemochromatosis, Iron Overload, Hereditary Hemochromatosis, Blood Donation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 622 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 1 Jan 2001 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 11 Dec 2000 (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 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.
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 MCV/hemoglobin 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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/HH patients | Other | Procedure: PhlebotomyHH patients |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. Up to 50 percent of the total study population may have received prior phlebotomy therapy.
- Elevated transferrin saturation and/or ferritin level, but diagnosis of HH not yet confirmed by genotype or liver biopsy.
- Elevated transferrin saturation and/or ferritin level without genotype findings listed above, but with elevated hepatic iron index on liver biopsy.
- Family member screening (unknown HH phenotype or genotype)
Key exclusion criteria (5 listed)
- Age less than 15 years.
- Pregnancy.
- Patients requiring therapeutic phlebotomy for reasons other than iron overload (polycythemia vera).
- Patients with iron overload not due to HH (e.g. hepatitis C infection, porphyria cutanea tarda, Wilson s disease, alpha-1-antitrypsin deficiency, alcohol abuse).
- Other medical illness or condition which, in the opinion of the Investigators, may contraindicate participation due to risk to patient or to Donor Center.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhlebotomyTherapeutic phlebotomy, the periodic, frequent removal of the iron contained in the hemoglobin of red blood cells. | Procedure or surgery | 1/HH patients |
Primary outcome
MCV drops 1-3% below baseline
Time frame: 4 to 12 months after starting phlebotomy therapy
Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Background: PubMed 9851897Lucotte G. Celtic origin of the C282Y mutation of hemochromatosis. Blood Cells Mol Dis. 1998 Dec;24(4):433-8. doi: 10.1006/bcmd.1998.0212.
- Background: PubMed 9162021Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, Schatzman RC. The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem. 1997 May 30;272(22):14025-8. doi: 10.1074/jbc.272.22.14025.
- Background: PubMed 8696333Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996 Aug;13(4):399-408. doi: 10.1038/ng0896-399.
- Background: PubMed 14617312Leitman SF, Browning JN, Yau YY, Mason G, Klein HG, Conry-Cantilena C, Bolan CD. Hemochromatosis subjects as allogeneic blood donors: a prospective study. Transfusion. 2003 Nov;43(11):1538-44. doi: 10.1046/j.1537-2995.2003.00570.x.
- Derived from this study: PubMed 24916507Wang X, Mendelsohn L, Rogers H, Leitman S, Raghavachari N, Yang Y, Yau YY, Tallack M, Perkins A, Taylor JG 6th, Noguchi CT, Kato GJ. Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Kruppel-like factor. Blood. 2014 Aug 7;124(6):946-54. doi: 10.1182/blood-2013-11-539718. Epub 2014 Jun 10.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Leonard N Chen, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Phlebotomy in people with Hemochromatosis, run by National Institutes of Health Clinical Center (CC) 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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 16 Sep 2026. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
MCV drops 1-3% below baseline (time frame: 4 to 12 months after starting phlebotomy therapy). 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 NCT00007150, which also lists 5 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 16 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.