Effectiveness of Arginine as a Treatment for Sickle Cell Anemia - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00513617

Purpose

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited genetic disease that can cause intense pain episodes. This study will evaluate the effectiveness of the nutritional supplement arginine at improving blood cell function and disease symptoms in people with SCD.

Condition	Intervention	Phase
Anemia, Sickle Cell	Drug: Arginine Other: Placebo	Phase II

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia

Drug Information available for: Nitric oxide Arginine Arginine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

NO levels, Gardos channel activity, and red blood cell density measurements [ Time Frame: Measured at Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Soluble vascular cell adhesion molecule (sVCAM), nitrotyrosine, 8-iso-PGF2a, ektacytometry, endothelial-1, fetal hemoglobin (HbF), and echocardiogram results [ Time Frame: Measured at Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
Number of hospitalizations, number of emergency department visits, and pain medication use [ Time Frame: Measured at Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	96
Study Start Date:	June 2004
Study Completion Date:	January 2008
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Low Dose: Active Comparator 0.05 g/kg/day	Drug: Arginine Depending on the weight of the child or adult, the patients took any where between 4-10 capsules 2 times a day. Patients weighing less than 45 kilograms were on the low dose active (or placebo) so the capsules were smaller. Patients greater than or equal to 45 kgs were on the high dose active or placebo, so these capsules were larger.
High Dose: Active Comparator 0.10 g/kg/day	Drug: Arginine Depending on the weight of the child or adult, the patients took any where between 4-10 capsules 2 times a day. Patients weighing less than 45 kilograms were on the low dose active (or placebo) so the capsules were smaller. Patients greater than or equal to 45 kgs were on the high dose active or placebo, so these capsules were larger.
Placebo: Placebo Comparator	Other: Placebo Depending on the weight of the child or adult, the patients took any where between 4-10 capsules 2 times a day. Patients weighing less than 45 kilograms were on the low dose active (or placebo) so the capsules were smaller. Patients greater than or equal to 45 kgs were on the high dose active or placebo, so these capsules were larger.

Detailed Description:

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain that are called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen. In people with SCD, the abnormal hemoglobin distorts the shape of the red blood cells. This causes the red blood cells to clump together, decreasing blood flow and oxygen delivery to the body's tissues. The reduced levels of oxygen can lead to sickle cell crises and tissue damage. Hemolysis, the destruction of red blood cells, is also a hallmark of SCD. During hemolysis, hemoglobin is released into the bloodstream, where it removes nitric oxide (NO), a natural chemical in the body that expands blood vessels. Arginase, another protein released during hemolysis, removes arginine from the bloodstream, which can also lead to decreased NO levels. The lack of NO constricts blood vessels, further contributing to painful sickle cell crises. Arginine supplementation may increase healthy hemoglobin and NO production and, in turn, prevent or reduce sickle cell crises. The purpose of this study is to evaluate the effectiveness of arginine at increasing NO levels, improving red blood cell function, and reducing hospitalizations and pain medication use in people with SCD.

This study will enroll children and adults with SCD. Participants will be randomly assigned to receive twice daily doses of either a low dose of arginine, a high dose of arginine, or placebo for 12 weeks. Study visits will occur at baseline, three times during Month 1, and Weeks 8, 12, 14, and 16. Each study visit will include an echocardiogram to measure heart activity, blood collection, and a medical history review to identify adverse events, pain medication usage, headaches, emergency department visits, and hospitalizations.

Eligibility

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Established diagnosis of H SS or S-beta thalassemia
History of at least one vaso-occlusive pain event in the 12 months prior to study entry
Regular compliance with comprehensive medical care
In a steady disease state and not in the midst of any acute complication due to SCD at study entry

Exclusion Criteria:

Inability to take or tolerate oral medications
Liver dysfunction (i.e., SGPT level greater than or equal to two times the normal limit and albumin level less than or equal to 3.2 g/dL)
Kidney dysfunction ( i.e., creatinine level greater than or equal to 1.2 mg/dL for children and greater than or equal to 1.4 mg/dL for adults)
Allergy to arginine
Pregnant
Received a blood transfusion within the 90 days prior to study entry
More than 10 hospital admissions for pain in the 12 months prior to study entry
Daily use of opioids and experiencing unstable pain that interferes with work or daily routine
Required more than 3 hospital admissions and more than 10 emergency department/day hospital visits in the 12 months prior to study entry
Received treatment with hydroxyurea within the 90 days prior to study entry
Received treatment with any investigational drug in the 90 days prior to study entry

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513617

Locations

United States, California
University of California - San Francisco
San Francisco, California, United States, 94143
Children's Hospital of Oakland and Research Institute
Oakland, California, United States, 94609
United States, Colorado
University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center
Denver, Colorado, United States, 80262
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Mississippi
University of Mississippi Medical Center (Pediatric)
Jackson, Mississippi, United States, 39215
University of Mississippi Medical Center (Adult)
Jackson, Mississippi, United States, 39215
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10463
Children's Hospital of Montefiore
Bronx, New York, United States, 10467
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oklahoma
Children's Hospital of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19444
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
St. Christopher's Children's Research Hospital
Philadelphia, Pennsylvania, United States, 19134
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75390

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Lillian McMahon, MD	Boston Medical Center
Principal Investigator:	Rathi Iyer, MD	University of Mississippi Medical Center (Pediatric)
Principal Investigator:	Carolyn Bigelow, MD	University of Mississippi Medical Center (Adult)
Principal Investigator:	Lennette Benjamin, MD	Montefiore Medical Center
Principal Investigator:	Mary Fabry, MD	Albert Einstein College of Medicine of Yeshiva University
Principal Investigator:	Thomas Moulton, MD	Children's Hospital of Montefiore
Principal Investigator:	Kim Smith-Whitley, MD	Children's Hospital of Philadelphia
Principal Investigator:	Laura DeCastro, MD	Duke University
Principal Investigator:	Kenneth Ataga, MD	The University of North Carolina, Chapel Hill
Principal Investigator:	Samir K. Ballas, MD	Thomas Jefferson University
Principal Investigator:	Sal Bertalone, MD	Norton Healthcare
Principal Investigator:	Carlton Dampier, MD	St. Christopher's Childrens Hospital
Principal Investigator:	William Mentzer, MD	University of California, San Francisco
Principal Investigator:	Winfred Wang, MD	St. Jude's Childrens Research Hospital
Principal Investigator:	Ulrike Reiss, MD	St. Jude Children's Research Hospital
Principal Investigator:	Cynthia Rutherford, MD	Children's Medical Center of Dallas
Principal Investigator:	Kathryn Hassell, MD	University of Colorado at Denver and Health Sciences Center
Principal Investigator:	Joan Parkhurst Cain, MD	Children's Hospital of Oklahoma

More Information

Responsible Party:	Childrens Hospital of Oakland and Research Institute ( Lori Styles/Principal Investigator )
Study ID Numbers:	485, U54 HL070587-04
Study First Received:	August 6, 2007
Last Updated:	January 18, 2008
ClinicalTrials.gov Identifier:	NCT00513617
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Sickle Cell Disease
Anemia
Nitric Oxide
Vaso Occlusive Events
Arginine Supplementation

Study placed in the following topic categories:

Nitric Oxide
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies

Anemia
Anemia, Hemolytic
Hemoglobinopathy
Anemia, Sickle Cell
Sickle cell anemia

ClinicalTrials.gov processed this record on January 15, 2009