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Protocol Details

Characterization of Cardiac Function in Subjects with Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

03-H-0282

Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 21 Years
Max Age: 100 Years

Referral Letter Required

No

Population Exclusion(s)

Children;
Pregnant Women

Keywords

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

Recruitment Keyword(s)

None

Condition(s)

Hereditary Hemochromatosis

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Heart, Lung, and Blood Institute

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.

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Eligibility

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will allow for inclusion.

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.

Use of beta-adrenergic blocking agents and calcium channel blockers with negative chronotropic effect within 1 week.

Inability to perform treadmill or bicycle exercise testing.

Inability to undergo MRI such as ferromagnetic implant.

Group B patients (treated 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.

Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will allow for inclusion.

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.

Use of beta-adrenergic blocking agents and calcium channel blockers with negative chronotropic effect within 1 week.

Inability to perform treadmill or bicycle exercise testing.

Inability to undergo MRI such as ferromagnetic implant.

Healthy volunteers

Group C Patients (Age-Gender Matched Healthy Control Subjects)

Pregnant or lactating women.

History or present evidence of any structural cardiac disease except mitral valve prolapse with mild mitral regurgitation, heart failure, peripheral vascular disease, coagulopathy, and uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic pressure over 100 mmHg).

Serum creatinine greater than 2.0 mg/ml.

LFT's more than 2.5 times above upper limit of normal.

Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will be included.

Uncontrolled glucose levels with hemoglobin A(1C) above 8 mg/dl or the use of 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.

Subjects with any chronic medical problems*

Inability to undergo MRI such as ferromagnetic implant.

*For the purpose of this protocol "chronic medical problems' is defined as any current condition not amenable to curative therapy and which requires long-term medical treatment and/or clinical monitoring.


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Citations:

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.

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.

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. Epub 2006 Jul 7.

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Contacts:

Principal Investigator

Referral Contact

For more information:

My-Le Nguyen, M.D.
National Heart, Lung and Blood Institute (NHLBI)
NIHBC 10 - CRC BG RM 5-1444
10 CENTER DR
BETHESDA MD 20892
(301) 451-3199
my-le.nguyen@nih.gov

Douglas R. Rosing, M.D.
National Heart, Lung and Blood Institute (NHLBI)
NIHBC 10 - CRC BG RM 6-3132
10 CENTER DR
BETHESDA MD 20892
(301) 451-8018
rosingd@nhlbi.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT00068159

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