Cardiac Function in Patients With Hereditary Hemochromatosis

NCT00068159 | Completed

• 2 other identifiers: 03028203-H-0282
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy. Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray. Participants will undergo the following tests and procedures over 2 to 5 days:

• Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test.
• Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be injected in an arm vein if needed to enhance the ultrasound images.
• Exercise stress echocardiography: The participant exercises on a stationary bike while heart function is measured with an echocardiogram, EKG, and blood pressure cuff.
• 24-hour Holter EKG: The participant wears a small machine that records heart rhythm continuously for 24 hours. The recorder is connected by cables to electrodes placed on the chest.
• Magnetic resonance imaging: This test uses a magnetic field and radio waves to obtain detailed images of the heart and blood vessels. The participant lies flat on a table that slides inside the scanner, which is a large hollow tube. All tests are performed once in normal volunteers and in patients who have received standard treatment for HH. Untreated patients repeat the tests 6 months after beginning phlebotomy or chelation. Additional time points for these tests might be added if further evaluation is needed.

Conditions

Hereditary Hemochromatosis

Keywords

Hereditary Disease; Diastolic Dysfunction; Exercise Tolerance; Exercise Stress Echocardiography; MRI; Natural History

Outcome Measures

Primary Outcomes (2)

• Echocardographic variable early diastolic peak tissue Doppler velocity of septal mitral annulus (Em).

  To assess detailed cardiac function using non-invasive cardiac imaging in Group A; untreated-NYHA Class I HH subjects without conventional therapy for HH, Group B; treated- NYHA Class I HH subjects with conventional phlebotomy and/or iron chelation therapy and compare these results to those from Group C; age-gender matched healthy control volunteers.

  5 year

• Exercise testing variable change in ejection fraction in response to exercise

  To compare the results of the cardiac functional abnormalities in HH to those from healthy control. volunteers. change in ejection fraction in response to exercise (change EF)

  5 year

Study Arms (3)

1

Untreated-NYHA Class I HH subjects without conventional therapy for HH

2

Treated- NYHA Class I HH subjects with conventional phlebotomy and/or iron chelation therapy

3

Age-gender matched healthy HH control volunteers

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from the North American continent and United States possessions. The patients currently followed at the Transfusion Medicine Department under IRB protocol # 01-CC-0045 will be informed of our study protocol. Also, subjects referred to IRB protocol # 01-CC-0045 from the ongoing genotyping study by the NHLBI (HEIRS trial) will be considered for the potential subjects. Advertisements of our study both on the Web and the NIH newsletters will be planned through the NIH Patient Recruitment and Public Liaison to recruit additional patients if necessary. There will be no exclusion from participation in the study on the basis of ethnicity/race/gender. Since HH is predominantly seen in Caucasian origins and the exact frequency in African, Asian, Hispanic population is too low to estimate, we assume that the study population will not be the same as the demographic representation of ethnic groups in this country because of the inheritance nature of this disease.

You may qualify if:

• HH Patients
• Group A patients (untreated HH patients)
• Adults 21 years or older
• New York Heart Association Functional Classification Class I
• Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%.
• Patient has not received standard chronic phlebotomy or deferoxamine treatment. Individuals are allowed to have up to 3 emergency phlebotomies for alleviation of severe iron accumulation before enrollment.
• Group B patients (treated HH patients)
• Adults 21 years or older
• New York Heart Association Functional Classification Class I
• Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%.
• Patient has been compliant with standard phlebotomy and/or deferoxamine treatment for 6 months or longer and in stable phase with iron saturation 50% or less.
• Healthy Volunteers
• Group C Patients (Age-Gender Matched Healthy Control Subjects)
• Adults 21 years or older.
• No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation.

You may not qualify if:

• HH patients
• Group A patients (untreated HH patients)
• Pregnant or lactating women
• History or present evidence of coronary artery disease, heart failure, peripheral vascular disease, coagulopathy, or uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic pressure over 100 mmHg).
• History of significant end-organ damage secondary to HH.
• Serum creatinine greater than 2.0 mg/ml
• LFT's more than 2.5 times above upper limit of normal
• History of structural cardiac disease except mitral valve prolapse with mild mitral regurgitation
• Uncontrolled glucose levels with hemoglobin A(1c) above 8 mg/dl or the use of more than one oral hyperglycemic agents or insulin therapy to control diabetes.
• Evidence of impaired immunity including HIV
• Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease.
• Participation in unrelated research involving investigational pharmacological agent in past 30 days.
• Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.
• Inability to provide informed consent
• Smoking in past 3 months.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Nguyen TT, Botello G, Sachdev V, Sidenko S, Ernst I, Waclawiw MA, Leitman SF, Rosing DR. Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis. Am J Cardiol. 2006 Oct 1;98(7):954-9. doi: 10.1016/j.amjcard.2006.04.040. Epub 2006 Aug 15.

  PMID: 16996882 BACKGROUND

• Shizukuda Y, Tripodi DJ, Smith KP, Arena R, Waclawiw MA, Rosing DR. Can we use heart rate recovery information generated by supine ergometry exercise? Am J Cardiol. 2006 Nov 1;98(9):1297-8. doi: 10.1016/j.amjcard.2006.07.009. Epub 2006 Aug 31. No abstract available.

  PMID: 17056351 BACKGROUND

• Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Smith KP, Sachdev V, Birdsall CW, Sidenko S, Waclawiw MA, Leitman SF, Rosing DR. Left ventricular systolic function during stress echocardiography exercise in subjects with asymptomatic hereditary hemochromatosis. Am J Cardiol. 2006 Sep 1;98(5):694-8. doi: 10.1016/j.amjcard.2006.03.055. Epub 2006 Jul 7.

  PMID: 16923464 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hemochromatosis; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

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

Study Officials

• My-Le Nguyen, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2003
• First Posted: September 9, 2003
• Study Start: December 8, 2003
• Primary Completion: November 12, 2010
• Study Completion: July 6, 2022
• Last Updated: May 3, 2024

Record last verified: 2024-05

Locations

US (1)