Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00068159
Status:
COMPLETED
Last Update Posted:
2024-05-03
First Post:
2003-09-09
Brief Title:
Cardiac Function in Patients With Hereditary Hemochromatosis
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization of Cardiac Function in Subjects With Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Hereditary hemochromatosis HH is the most common hereditary metabolic abnormality among Caucasians Homozygosity for the Cys282Tyr mutation which is the most common known mutation with a predisposition to iron overload occurs with an estimated frequency of 8 per 1000 in the Caucasians Hemochromatosis in its advanced stages is associated with severe cardiac complications including congestive heart failure premature coronary artery disease and cardiac arrhythmias The clinical manifestations of HH are due to increased iron absorption and abnormal iron cycling with excessive iron deposition in various organs Mutations of the Hfe gene on chromosome 6 have been recently identified Although the pathophysiology remains incompletely understood a homozygote mutation in Cys282Tyr is present in 84 to 100 of clinically confirmed HH cases This discovery permits the early diagnosis of this disease and could be used for screening to identify asymptomatic cases Therefore the NHLBI in January 2000 launched a 30 million dollar project named HEIRS HEmochromatosis and IRon overload Study to screen 1000000 adults for HH and recently completed enrollment
TAB
Increased left ventricular wall thickness and mass has been found to be early cardiac manifestations of HH appearing before the onset of contractile dysfunction Interestingly a report also indicates that functional abnormalities of the heart can be seen in predominantly asymptomatic HH patient group Such abnormalities of diastolic function are detected by Doppler echocardiography Observations support the theory that asymptomatic cardiac dysfunction is detectable with non-invasive cardiac imaging in patients with HH TAB
TAB
Although the pathophysiology of cardiac dysfunction in HH has not been well characterized it is speculated that enhanced production of reactive oxygen species ROS may be responsible for tissue damage Therefore biochemical andor genetic markers of oxidant stress might be helpful in determining whether this mechanism is involved in producing cardiac dysfunction
In this protocol we propose a retrospective pilot study with a small-sized nested prospective study of cardiac function in patients with HH The intention is to utilize obtained results to design a larger definitive study if results are warranted The following hypotheses will be tested Cardiac abnormalities 1 can be diagnosed with conventional non-invasive cardiac imaging in HH patients with New York Heart Association Functional Class I asymptomatic 2 limit patients exercise capacity 3 are associated with an elevated oxidant stress level and 4 are improved by phlebotomy and its efficacy correlated with a reduction in oxidant stress
TAB
Increased left ventricular wall thickness and mass has been found to be early cardiac manifestations of HH appearing before the onset of contractile dysfunction Interestingly a report also indicates that functional abnormalities of the heart can be seen in predominantly asymptomatic HH patient group Such abnormalities of diastolic function are detected by Doppler echocardiography Observations support the theory that asymptomatic cardiac dysfunction is detectable with non-invasive cardiac imaging in patients with HH TAB
TAB
Although the pathophysiology of cardiac dysfunction in HH has not been well characterized it is speculated that enhanced production of reactive oxygen species ROS may be responsible for tissue damage Therefore biochemical andor genetic markers of oxidant stress might be helpful in determining whether this mechanism is involved in producing cardiac dysfunction
In this protocol we propose a retrospective pilot study with a small-sized nested prospective study of cardiac function in patients with HH The intention is to utilize obtained results to design a larger definitive study if results are warranted The following hypotheses will be tested Cardiac abnormalities 1 can be diagnosed with conventional non-invasive cardiac imaging in HH patients with New York Heart Association Functional Class I asymptomatic 2 limit patients exercise capacity 3 are associated with an elevated oxidant stress level and 4 are improved by phlebotomy and its efficacy correlated with a reduction in oxidant stress
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-H-0282 | None | None | None |