Oral Nifedipine to Treat Iron Overload

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00712738
First received: July 9, 2008
Last updated: May 10, 2012
Last verified: September 2010
  Purpose

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.

...


Condition Intervention Phase
Thalassemia
Iron Overload
Hemochromatosis
Drug: Nifedipine
Procedure: Phlebotomy
Procedure: Urinalysis
Procedure: Echocardiogram
Procedure: Electrocardiogram
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Oral Nifedipine for the Treatment of Iron Overload

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Evaluate nifedipine-related urinary iron excretion.

Secondary Outcome Measures:
  • Evaluate potential for nifedipine to increase urinary iron excretion among patients with iron overload.

Enrollment: 6
Study Start Date: June 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Nifedipine
    N/A
    Procedure: Phlebotomy
    N/A
    Procedure: Urinalysis
    N/A
    Procedure: Echocardiogram
    N/A
    Procedure: Electrocardiogram
    N/A
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00712738

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Responsible Party: Jeffery L. Miller, M.D./National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00712738     History of Changes
Other Study ID Numbers: 080157, 08-DK-0157
Study First Received: July 9, 2008
Last Updated: May 10, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Nifedipine
Thalassemia
Hemochromatosis
Iron Overload
Iron Excretion

Additional relevant MeSH terms:
Hemochromatosis
Thalassemia
Iron Overload
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Nifedipine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014