Oral Nifedipine to Treat Iron Overload

NCT00712738 | Completed Phase 1

• 2 other identifiers: 08015708-DK-0157
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Thalassemia; Iron Overload; Hemochromatosis

Keywords

Nifedipine; Thalassemia; Hemochromatosis; Iron Overload; Iron Excretion

Outcome Measures

Primary Outcomes (1)

• Evaluate nifedipine-related urinary iron excretion.

Secondary Outcomes (1)

• Evaluate potential for nifedipine to increase urinary iron excretion among patients with iron overload.

Interventions

Nifedipine DRUG

Phlebotomy PROCEDURE

Urinalysis PROCEDURE

Echocardiogram PROCEDURE

Electrocardiogram PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, Aydinok Y, Kattamis A, Kilinc Y, Porter J, Capra M, Galanello R, Fattoum S, Drelichman G, Magnano C, Verissimo M, Athanassiou-Metaxa M, Giardina P, Kourakli-Symeonidis A, Janka-Schaub G, Coates T, Vermylen C, Olivieri N, Thuret I, Opitz H, Ressayre-Djaffer C, Marks P, Alberti D. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1;107(9):3455-62. doi: 10.1182/blood-2005-08-3430. Epub 2005 Dec 13.

  PMID: 16352812 BACKGROUND

• Barton JC. Chelation therapy for iron overload. Curr Gastroenterol Rep. 2007 Mar;9(1):74-82. doi: 10.1007/s11894-008-0024-9.

  PMID: 17335681 BACKGROUND

• Ludwiczek S, Theurl I, Muckenthaler MU, Jakab M, Mair SM, Theurl M, Kiss J, Paulmichl M, Hentze MW, Ritter M, Weiss G. Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med. 2007 Apr;13(4):448-54. doi: 10.1038/nm1542. Epub 2007 Feb 11.

  PMID: 17293870 BACKGROUND

• Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.

  PMID: 37975597 DERIVED

MeSH Terms

Conditions

Thalassemia; Iron Overload; Hemochromatosis

Interventions

Nifedipine; Phlebotomy; Urinalysis

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 9, 2008
• First Posted: July 10, 2008
• Study Start: June 20, 2008
• Primary Completion: September 22, 2010
• Study Completion: September 22, 2010
• Last Updated: July 2, 2017

Record last verified: 2010-09-22

Locations

US (1)