NCT00056433

Evaluation of Hydroxyurea Plus L-arginine or Sildenafil to Treat Sickle Cell Anemia

Completed Phase 1 Last updated 22 November 2019

What this trial tests

Phase 1 trial testing Hydroxyurea in Sickle Cell Anemia in 39 participants. Completed in 27 December 2006.

Timeline

10 March 2003

Primary endpoint
27 December 2006

27 December 2006

Quick facts

Lead sponsor	National Institutes of Health Clinical Center (CC)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	39
Start date	10 March 2003
Primary completion	27 December 2006
Estimated completion	27 December 2006
Sites	1 location across United States

Drugs / interventions tested

• Hydroxyurea — full drug profile →
• L-Arginine — full drug profile →
• Sildenafil (sildenafil) — full drug profile →

Conditions studied

• Sickle Cell Anemia — all drugs for Sickle Cell Anemia →

Sponsor

National Institutes of Health Clinical Center (CC)

Who can join

16 and older, any sex, with Sickle Cell Anemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Hematologic, biochemical, and cardiopulmonary effects of L-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy.
   Little JA, Hauser KP, Martyr SE, Harris A, et al · · 2009 · cited 47× · PMID 19215288 · DOI 10.1111/j.1600-0609.2009.01210.x