A Phase 2 interventional study of Phlebotomy in Hemochromatosis, sponsored by National Institutes of Health Clinical Center (CC). Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by National Institutes of Health Clinical Center (CC) · Phase 2, Interventional, and Diagnostic
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:
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.
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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.
55 studies on the registry are indexed under Hemochromatosis; 4 are open to participants now.
This study's enrollment of 622 is above the median of 61 across 30 interventional studies indexed under Hemochromatosis.
Browse Hemochromatosis studies →National Institutes of Health Clinical Center (CC) is the lead sponsor of 375 studies on the registry; 27 are open to participants now.
Of its 23 completed or terminated interventional studies of FDA-regulated products, 19 (83%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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 .
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)
EXCLUSION CRITERIA:
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. 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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HH patients
Procedure: Phlebotomy
Therapeutic phlebotomy, the periodic, frequent removal of the iron contained in the hemoglobin of red blood cells.
MCV drops 1-3% below baseline
Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion
Time frame: 4 to 12 months after starting phlebotomy therapy
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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