Effectiveness of Arginine as a Treatment for Sickle Cell Anemia

Anemia, Sickle Cell Clinical Trial

— Arginine  

Official title:

Arginine Supplementation in Sickle Cell Anemia: Physiological and Prophylactic Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513617
• Other study ID #: 485
• Secondary ID: U54HL070587-04
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2007
• Last updated: June 19, 2009
• Start date: June 2004
• Est. completion date: January 2008

Study information

• Verified date: June 2009
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: January 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell

Intervention

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
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.

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts
United States	Children's Hospital of Montefiore	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Mississippi Medical Center (Adult)	Jackson	Mississippi
United States	University of Mississippi Medical Center (Pediatric)	Jackson	Mississippi
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Oakland and Research Institute	Oakland	California
United States	Children's Hospital of Oklahoma	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Children's Research Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of California - San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gardos Channel Activity		12 weeks after randomization	No
Primary	Nitric Oxide		12 weeks after randomization	No
Primary	Mean Corpuscular Hemoglobin Concentration		12 weeks after randomization	No
Secondary	Soluble Vascular Cell Adhesion Molecule		12 weeks after randomization	No
Secondary	8-Iso-PGF2a		12 weeks after randomization	No
Secondary	Endothelin-1		12 weeks after randomization	No
Secondary	Fetal Hemoglobin		12 weeks after randomization	No