Treatment of Hemochromatosis

NCT00007150 | Active Not Recruiting Phase 2

• 2 other identifiers: 01004501-CC-0045
• Study Type: interventional
• Target: 622
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemochromatosis

Keywords

Phlebotomy Therapy; Hemochromatosis; Iron Overload; Hereditary Hemochromatosis; Blood Donation

Outcome Measures

Primary Outcomes (1)

• MCV drops 1-3% below baseline

  Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion

  4 to 12 months after starting phlebotomy therapy

Study Arms (1)

1/HH patients

OTHER

HH patients

Procedure: Phlebotomy

Interventions

Phlebotomy PROCEDURE

Therapeutic phlebotomy, the periodic, frequent removal of the iron contained in the hemoglobin of red blood cells.

1/HH patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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.

  PMID: 9851897 BACKGROUND

• Feder 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.

  PMID: 9162021 BACKGROUND

• Feder 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.

  PMID: 8696333 BACKGROUND

• Leitman 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.

  PMID: 14617312 BACKGROUND

• Wang 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.

  PMID: 24916507 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hemochromatosis; Iron Overload

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Leonard N Chen, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2000
• First Posted: December 11, 2000
• Study Start: January 1, 2001
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-02-06

Locations

US (1)