Protocol Details

Evaluation of Potential Synergy of Combining Hydroxyurea with Nitric Oxide Donors on Fetal Hemoglobin Synthesis in Patients with Sickle Cell Anemia

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number	03-CC-0127
Sponsoring Institute	National Institutes of Health Clinical Center (CC)
Recruitment Detail	Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 16 Max Age: N/A
Referral Letter Required	No
Population Exclusion(s)	None
Special Instructions	Currently Not Provided
Keywords	Fetal Hemoglobin Induction; L-Arginine; Nitric Oxide Therapy; Sickle Cell Disease; Sildenafil (Viagra)
Recruitment Keyword(s)	Sickle Cell Anemia
Condition(s)	Sickle Cell Anemia
Investigational Drug(s)	Hydroxyurea L-Arginine Sildenafil
Investigational Device(s)	None
Intervention(s)	Drug: Hydroxyurea Drug: L-Arginine Drug: Sildenafil
Supporting Site	NIH Clinical Center

Patients with sickle cell disease have abnormal hemoglobin (the protein in red blood cells that carries oxygen to the body). This abnormality causes red blood cells to take on a sickle shape, producing disease symptoms. Fetal hemoglobin, a type of hemoglobin present in fetuses and babies, can prevent red cells from sickling. The drug hydroxyurea increases fetal hemoglobin production in patients with sickle cell disease by making a molecule called nitric oxide. The drugs L-arginine and Sildenafil (Viagra) increase the amount or the effect of nitric oxide. This study will evaluate:

- The safety of giving L-arginine or Sildenafil together with hydroxyurea in patients with sickle cell disease;

- The effectiveness of L-arginine plus hydroxyurea or Sildenafil plus hydroxyurea in increasing fetal hemoglobin in patients with sickle cell disease; and

- The effectiveness of L-arginine plus hydroxyurea or Sildenafil and hydroxyurea in lowering blood pressure in the lungs of patients with sickle cell disease. (Pulmonary blood pressure is elevated in about one-third of patients with sickle cell disease, and this condition increases the risk of dying from the disease.)

Patients with hemoglobin S-only, S-beta-thalassemia, or other sickle cell disease genotype may be eligible for this study.

Before starting treatment, patients will have a complete medical history and physical examination. All patients will take hydroxyurea once a day every day by mouth for at least 2 months. They will be admitted to the NIH Clinical Center to take their first dose of hydroxyurea, and will have blood drawn through a catheter (plastic tube placed in a vein) every hour for 6 hours for tests to determine nitric oxide levels. After discharge, they will return to the clinic once every 2 weeks to check for treatment side effects and for blood tests to monitor hemoglobin and fetal hemoglobin levels. After fetal hemoglobin levels have been stable for 2 months, patients will be admitted to the Clinical Center for their first dose of L-arginine (for men) or Sildenafil (for women). Again, blood samples will be collected through a catheter once an hour for 6 hours. If there are no complications, patients will be discharged and will continue taking hydroxyurea once a day and L-arginine or Sildenafil three times a day for at least 3 months until fetal hemoglobin levels have been stable for at least 2 months. Patients will return to the clinic for blood tests every week for 2 weeks and then every 2 weeks to monitor hemoglobin and fetal hemoglobin levels and to check for treatment side effects.

Patients will have eye examinations before and during treatment. Some patients with sickle cell disease develop abnormalities in the blood vessels of the eye. Also, Sildenafil can cause temporary changes in color vision. Rarely, more serious eye problems can occur, such as bleeding from the eye blood vessels or damage to the retina-a layer of tissue that lines the back of the eye. Patients will also have an echocardiogram (ultrasound of the heart) before beginning treatment, after hydroxyurea treatment, and after 1 and 3 months of combined treatment with hydroxyurea and L-arginine or Sildenafil to help measure blood pressure in the lungs.

Patients who develop complications from L-arginine or Sildenafil may continue in the study on hydroxyurea alone. Patients whose fetal hemoglobin levels increase with the combination therapy of hydroxyurea and L-arginine or Sildenafil may continue to take them.

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Eligibility

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

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Citations:

Rodgers GP, et al. Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea. N Engl J Med. 1990 Apr 12;322(15):1037-45.

Goldberg MA, et al. Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N Engl J Med. 1990 Aug 9;323(6):366-72.

Charache S, et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood. 1992 May 15;79(10):2555-65.

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Contacts:

Principal Investigator	Referral Contact	For more information http://clinicalstudies.info.nih.gov.
Gregory J. Kato, M.D. National Institutes of Health Clinical Center (CC) National Institutes of Health Two Democracy Plaza Room 201A 6707 Democracy Boulevard Bethesda, Maryland 20817 (301) 402-6056 gavellif@cc.nih.gov	James Nichols, R.N. National Institutes of Health Clinical Center (CC) National Institutes of Health Building 10 Room 1-1469 10 Center Drive Bethesda, Maryland 20892 (301) 496-4733 sara.sadeghi@nih.gov	Patient Recruitment and Public Liaison Office Building 61 10 Cloister Court Bethesda, Maryland 20892-4754 Toll Free: 1-800-411-1222 TTY: 301-594-9774 (local),1-866-411-1010 (toll free) Fax: 301-480-9793 prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT00056433

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