Oral Nifedipine to Treat Iron Overload
| Status: | Completed |
|---|---|
| Conditions: | Hematology, Hematology, Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | June 2008 |
| End Date: | September 2010 |
A Trial of Oral Nifedipine for the Treatment of Iron Overload
This study will determine if nifedipine, a medication used to treat high blood pressure, can
help treat iron overload, a condition in which the body contains too much iron. Iron
overload can be caused by the body's inability to regulate iron or by medical treatments,
such as multiple blood transfusions. Over time, it can cause problems with the liver, heart
and glands. Treatments include reducing iron intake in the diet or removing the excess iron
using medical therapies. Recently, nifedipine was found to cause iron loss in the urine of
small animals. This study will see if the drug can increase the removal of iron into the
urine in humans as well.
People 18 years of age and older with iron overload may be eligible for this study to
undergo the following procedures:
Study Day 1
Participants come to the NIH Clinical Center for a medical history, physical examination,
blood and urine tests, electrocardiogram (EKG) and echocardiogram (heart ultrasound).
Study Day 2
Participants will collect three urine samples: one is collected over 4 hours, followed by a
second over 4 hours. Both of these samples are collected at NIH in the outpatient day
hospital. At home, a third urine sample will be collected over 16 hours. For 1 week before
the collections, participants are asked not to drink tea or eat foods high in Vitamin C or
iron. They are also asked not to take any iron chelating medications.
Study Day 3
Participants repeat the same urine collections as on day 2. They collect a 4-hour urine
sample at the outpatient day hospital at NIH. They will then take a 20-mg tablet of
nifedipine, and remain in the clinic 4 hours for blood pressure monitoring. A second urine
sample during this time. They then return home to collect the final 16-hour sample, which
they bring to the clinic the following day. Again, they are instructed to avoid a diet high
in vitamin C, iron rich foods, tea, and to avoid taking any iron chelating medications.
help treat iron overload, a condition in which the body contains too much iron. Iron
overload can be caused by the body's inability to regulate iron or by medical treatments,
such as multiple blood transfusions. Over time, it can cause problems with the liver, heart
and glands. Treatments include reducing iron intake in the diet or removing the excess iron
using medical therapies. Recently, nifedipine was found to cause iron loss in the urine of
small animals. This study will see if the drug can increase the removal of iron into the
urine in humans as well.
People 18 years of age and older with iron overload may be eligible for this study to
undergo the following procedures:
Study Day 1
Participants come to the NIH Clinical Center for a medical history, physical examination,
blood and urine tests, electrocardiogram (EKG) and echocardiogram (heart ultrasound).
Study Day 2
Participants will collect three urine samples: one is collected over 4 hours, followed by a
second over 4 hours. Both of these samples are collected at NIH in the outpatient day
hospital. At home, a third urine sample will be collected over 16 hours. For 1 week before
the collections, participants are asked not to drink tea or eat foods high in Vitamin C or
iron. They are also asked not to take any iron chelating medications.
Study Day 3
Participants repeat the same urine collections as on day 2. They collect a 4-hour urine
sample at the outpatient day hospital at NIH. They will then take a 20-mg tablet of
nifedipine, and remain in the clinic 4 hours for blood pressure monitoring. A second urine
sample during this time. They then return home to collect the final 16-hour sample, which
they bring to the clinic the following day. Again, they are instructed to avoid a diet high
in vitamin C, iron rich foods, tea, and to avoid taking any iron chelating medications.
Iron overload is common worldwide. If left untreated, body iron overload leads to multiple
organ abnormalities including hepatic, endocrine (diabetes) and cardiac failure. In patients
with ineffective erythropoiesis, iron overload results from the combination of increased
intestinal absorption and transfusion. Unfortunately, physiological means to remove excess
iron are limited, and treatments are limited to therapeutic phlebotomy and chelation
therapy. While phlebotomy is the preferred therapy for patients with hemochromatosis,
therapy for anemic patients is largely limited to chelation drugs. Since those drugs are
frequently inadequate, additional iron-reduction therapies are being sought. Based upon
recently published data in a rodent model, the purpose of this study is to determine if
nifedipine will increase iron excretion in the urine among humans with increased levels of
iron. Volunteers will be given a single oral dose (20mg) of nifedipine. Iron level in
collections of urine will be measured and compared before and after nifedipine to determine
if there is an associated increase in urinary iron excretion.
organ abnormalities including hepatic, endocrine (diabetes) and cardiac failure. In patients
with ineffective erythropoiesis, iron overload results from the combination of increased
intestinal absorption and transfusion. Unfortunately, physiological means to remove excess
iron are limited, and treatments are limited to therapeutic phlebotomy and chelation
therapy. While phlebotomy is the preferred therapy for patients with hemochromatosis,
therapy for anemic patients is largely limited to chelation drugs. Since those drugs are
frequently inadequate, additional iron-reduction therapies are being sought. Based upon
recently published data in a rodent model, the purpose of this study is to determine if
nifedipine will increase iron excretion in the urine among humans with increased levels of
iron. Volunteers will be given a single oral dose (20mg) of nifedipine. Iron level in
collections of urine will be measured and compared before and after nifedipine to determine
if there is an associated increase in urinary iron excretion.
- INCLUSION CRITERIA:
Iron overloaded subjects will have a history of iron overload that may be due to a variety
of causes including genetic hemochromatosis or thalassemia or other transfusion-dependent
anemias (e.g. sickle cell syndromes, aplastic anemia, ineffective erythropoiesis) or other
causes. Entry into the study requires that all subjects possess at least minimal evidence
of iron overload at the time of entry (defined as serum ferritin and serum transferrin
saturations levels above the normal range). Among fifty (50) subjects recruited for this
protocol, at least twenty (20) with significant iron overload (defined in this study as
ferritin greater than 500 ng/ml and transferrin saturation greater than (50%) will be
included.
All subjects will be of adult age (greater than or equal to 18 yrs).
All subjects enrolled in this protocol will have a primary physician and care in the
community that is capable of managing any medical problems unrelated to the nifedipine
regimen.
All subjects must be able to provide informed consent.
EXCLUSION CRITERIA:
Allergy to nifedipine.
Patient receiving calcium channel blocker therapy within 7 days prior to enrollment.
Blood transfusion within 7 days of first urine iron evaluation.
Pregnant or lactating women.
Patients with GFR less than 60 ml/min.
Albumin less than 3g/dl.
Significant hemoglobinuria (greater than1+ on urinalysis).
Hemoglobin less than 10 g/dl
Uncompensated cardiac disease including decreased ejection fraction detected by
echocardiogram, angina, hypotension (less than 90mmHg systolic pressure) or symptomatic
arrhythmias. Documented myocardial infarction within one year prior to the study.
Use of tea, Vitamin C, iron chelation therapy, iron supplements, grapefruit juice,
cimetidine, digitalis, quinidine, or beta-blockers (due to potential for increased serum
drug levels versus cardiovascular risk) within 7 days prior to the study.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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