Clinical Trial: Treatment of Hemochromatosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Studies of Phlebotomy Therapy in Hereditary Hemochromatosis

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 phlebot

    Detailed Summary:

    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 H
    Sponsor: National Institutes of Health Clinical Center (CC)

    Current Primary Outcome:

    • To prospectively study the response to to phlebotomy therapy in patients with hereditary hemochromatosis using changes in the MCV/hemoglobin as the primary monitoring guide for the pace of iron-depletion, to compare the efficacy of the MCV gu... [ Time Frame: Ongoing ]
    • To prospectively evaluate the effect of maintaining a long-term state of borderline iron-limited erythropoiesis (MCV 1-3% below baseline) on the frequency of phlebotomy during the maintenance phase oftherapy and on the progression of hemoc... [ Time Frame: Ongoing ]
    • To establish a program to make blood therapeutically withdrawn fromhemochromatosis subjects available for allogeneic transfusion to patients in the Clinical Center, NIH. [ Time Frame: Ongoing ]


    Original Primary Outcome:

    Current Secondary Outcome: To prospectively evaluate the effect of maintaining a long-term state of iron-limited erythropoiesis on the progression of hemochromatosis-associated cirrhosis. [ Time Frame: Ongoing ]

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: December 9, 2000
    Date Started: December 6, 2000
    Date Completion:
    Last Updated: April 21, 2017
    Last Verified: March 6, 2017